Autism spectrum disorder(ASD)is a group of heterogeneous,multi-factorial,neurodevelopmental disorders resulting from genetic and environmental factors interplay.Infection is a significant trigger of autism,especially ...Autism spectrum disorder(ASD)is a group of heterogeneous,multi-factorial,neurodevelopmental disorders resulting from genetic and environmental factors interplay.Infection is a significant trigger of autism,especially during the critical developmental period.There is a strong interplay between the viral infection as a trigger and a result of ASD.We aim to highlight the mutual relationship between autism and viruses.We performed a thorough literature review and included 158 research in this review.Most of the literature agreed on the possible effects of the viral infection during the critical period of development on the risk of developing autism,especially for specific viral infections such as Rubella,Cytomegalovirus,Herpes Simplex virus,Varicella Zoster Virus,Influenza virus,Zika virus,and severe acute respiratory syndrome coronavirus 2.Viral infection directly infects the brain,triggers immune activation,induces epigenetic changes,and raises the risks of having a child with autism.At the same time,there is some evidence of increased risk of infection,including viral infections in children with autism,due to lots of factors.There is an increased risk of developing autism with a specific viral infection during the early developmental period and an increased risk of viral infections in children with autism.In addition,children with autism are at increased risk of infection,including viruses.Every effort should be made to prevent maternal and early-life infections and reduce the risk of autism.Immune modulation of children with autism should be considered to reduce the risk of infection.展开更多
Plus-strand RNA virus replication occurs in tight association with cytoplasmic host cell membranes. Both, viral and cellular factors cooperatively generate distinct organelle-like structures, designated viral replicat...Plus-strand RNA virus replication occurs in tight association with cytoplasmic host cell membranes. Both, viral and cellular factors cooperatively generate distinct organelle-like structures, designated viral replication factories. This compartmentalization allows coordination of the different steps of the viral replication cycle, highly efficient genome replication and protection of the viral RNA from cellular defense mechanisms. Electron tomography studies conducted during the last couple of years revealed the three dimensional structure of numerous plus-strand RNA virus replication compartments and highlight morphological analogies between different virus families. Based on the morphology of virusinduced membrane rearrangements, we propose two separate subclasses: the invaginated vesicle/spherule type and the double membrane vesicle type. This review discusses common themes and distinct differences in the architecture of plus-strand RNA virus-induced membrane alterations and summarizes recent progress that has been made in understanding the complex interplay between viral and co-opted cellular factors in biogenesis and maintenance of plus-strand RNA virus replication factories.展开更多
Elimination of viral hepatitis in sub-Saharan Africa by 2030 is an ambitious feat.However,as stated by the World Health Organization,there are unprecedented opportunities to act and make significant contributions to t...Elimination of viral hepatitis in sub-Saharan Africa by 2030 is an ambitious feat.However,as stated by the World Health Organization,there are unprecedented opportunities to act and make significant contributions to the elimination target.With 60 million people chronically infected with hepatitis B virus(HBV)of whom 38800 are at risk of developing highly fatal hepatocellular carcinoma(HCC)every year,sub-Saharan Africa faces one of the greatest battles towards elimination of viral hepatitis.There is a need to examine progress in controlling the disproportionate burden of HBV-associated HCC in sub-Saharan Africa within the context of this elimination target.By scaling-up coverage of hepatitis B birth dose and early childhood vaccination,we can significantly reduce new cases of HCC by as much as 50%within the next three to five decades.Given the substantial reservoir of chronic HBV carriers however,projections show that HCC incidence and mortality rates in sub-Saharan Africa will double by 2040.This warrants urgent public health attention.The trends in the burden of HCC over the next two decades,will be determined to a large extent by progress in achieving early diagnosis and appropriate linkage to care for high-risk chronic HBV infected persons.展开更多
Hepatitis C virus(HCV)infection is the leading cause of chronic liver-related diseases,including cirrhosis,liver failure,and hepatocellular carcinoma.Currently,no effective vaccine is available for HCV infection.Polye...Hepatitis C virus(HCV)infection is the leading cause of chronic liver-related diseases,including cirrhosis,liver failure,and hepatocellular carcinoma.Currently,no effective vaccine is available for HCV infection.Polyethylene glycol interferon-α(PegIFN-α)in combination with ribavirin(RBV)is the standard of care(SOC)for chronic hepatitis C.However,the efficacy of PegIFN-αand RBV combination therapy is less than 50%for genotype 1HCV,which is the dominant virus in humans.In addition,IFN and RBV have several severe side effects.Therefore,strategies to improve sustained virological response(SVR)rates have been an important focus for clinical physicians.The serine protease inhibitors telaprevir and boceprevir were approved by the United States Food and Drug Administration in 2011.The addition of HCV protease inhibitors to the SOC has significantly improved the efficacy of treatments for HCV infection.Several direct-acting antiviral drugs currently in late-stage clinical trials,both with and without pegIFN and RBV,have several advantages over the previous SOC,including higher specificity and efficacy,fewer side effects,and the ability to be administered orally,and might be optimal regimens in the future.Factors affecting the efficacy of anti-HCV treatments based on IFN-αinclude the HCV genotype,baseline viral load,virological response during treatment,host IL28B gene polymorphisms and hepatic steatosis.However,determining the effect of the above factors on DAA therapy is necessary.In this review,we summarize the development of antiHCV agents and assess the main factors affecting the efficacy of antiviral treatments.展开更多
Many mammalian herpes viruses utilize heparan sulfate (HS) moieties present on cell surface proteoglycans as receptors for cell entry, and this process also requires viral glycoprotein C (gC) homologues. However, ...Many mammalian herpes viruses utilize heparan sulfate (HS) moieties present on cell surface proteoglycans as receptors for cell entry, and this process also requires viral glycoprotein C (gC) homologues. However, our understanding of the role of gC in facilitating attachment of other alpha-herpes viruses such as the duck plague virus (DPV) remains preliminary. To study the role of gC during DPV infection, we used a gC-deleted mutant virus (DPV-AgC-EGFP). Examination of the viral copy number by real-time PCR, as well as time course studies of viral adsorption and proliferation revealed that gC was involved in the viral binding to the cell surface. The affinity of viral glycoproteins (gB-DPV, gC-DPV, and gE-DPV) to HS was assessed using a prokaryotic expression system and HJTrapTM HeparJn HP column chromatography. In addition, to confirm that gC played a role in the interaction between DPV and HS, viruses were treated with the HS analogue heparin and host cells were treated with its inhibitors heparinase prior to exposure to DPV-△gC-EGFP or wild-type strain Chinese virulent duck plague virus (DPV-CHv). The effects of heparin and heparinase on virus infectivity demonstrated that function of gC on Viral adsorption is independent of interactions between gC and heparin sulfate on cell surface. All in all, this study demonstrated that the gC of DPV can mediate viral adsorption in an HS-independent manner, which distinguish it from the gC of some other alpha-herpes viruses. Future studies will be required to identify the receptors involved in gC protein binding to cells. This work provides us a foundation for further studies of examining the roles of gC in the adsorption during duck plague virus infection.展开更多
Bluetongue (BT) is a serious hemorrhagic disease of ruminants caused by bluetongue virus (BTV). Inactive BTV vaccines have been successful in field trials in some areas, and inactivated vaccines are considered safer. ...Bluetongue (BT) is a serious hemorrhagic disease of ruminants caused by bluetongue virus (BTV). Inactive BTV vaccines have been successful in field trials in some areas, and inactivated vaccines are considered safer. However, information about the effect of the viral antigen level on the serological response and efficiency of the inactive BTV-16 vaccine is lacking. In the present study, the serological response and efficiency of the viral antigen concentration in the binary ethylenimine-inactivated Chinese BTV serotype-16 vaccine were investigated. The viral antigens in the viral suspension (VS) were quantified using a modified BTV AC-ELISA method. Four batches of vaccine containing 1, 5, 10, and 50 μg/ml of viral antigen were generated from the VS. Four groups of naive Chinese sheep were vaccinated with the different vaccine batches, and the serological response and vaccine efficiency were investigated before and after challenge infection. The vaccines containing 10 and 50 μg/ml of viral antigen induced significant ELISA and neutralizing antibody titers 14 days after vaccination, whereas the vaccines containing 1 and 5 μg/ml of viral antigen did not have these effects. A booster immunization at 21 days enhanced all groups’ antibody titers;however, the increased titer was related to the viral antigen level. In contrast to the serological response, the viral antigen level of the vaccines did not have a significant effect on the vaccine efficiency. With the exception of one sheep from the 5 μg/ml viral antigen group, all vaccinated sheep from the four antigen level groups showed strong resistance to infection based on their clinical symptoms, rectal temperatures and viremia. Collectively, these data suggested that viral antigen levels from 1 to 50 μg/ml had a significant effect on the serological response of the animals but a limited effect on the vaccine efficiency. The BTV-16 vaccine containing 1 μg/ml of viral antigen was sufficient to achieve high efficiency, but only the vaccines with more than 10 μg/ml of antigen induced a significant antibody response. To obtain a better serological response, we suggest the use of vaccines with more than 10 μg/ml of viral antigen. The findings in the study will be useful for BTV vaccine production.展开更多
Objective:Qingfei oral liquid(QF),an experimental Chinese medicine prescription developed from the ancient priscription of traditional Chinese medicines Ma Xin Shi Gan decoction and Tingli Dazao Xie Fei decoction,has ...Objective:Qingfei oral liquid(QF),an experimental Chinese medicine prescription developed from the ancient priscription of traditional Chinese medicines Ma Xin Shi Gan decoction and Tingli Dazao Xie Fei decoction,has been effectively used since decades to treat patients with viral pneumonia and asthma.In our previous study,we had demonstrated that QF can significantly reduce airway hyperresponsiveness,hyperemia,lung tissue edema,inflammatory lung tissue infiltration in mice,airway mucus secretion,and peripheral airway collagen hyperplasia;however,its mechanism of action is unknown.Methods:Fifty 6–8-week-old male BALB/c mice were equally and randomly divided into five groups:the control,ovalbumin(OVA),OVA+respiratory syncytial virus(RSV),QF,and dexamethasone(Dxms)groups.The QF group was administered QF at 1.17 g·kg−1·d−1,the Dxms group received dexamethasone injections at 0.2 mg·kg−1·d−1,and the remaining groups were administered PBS.Inflammation in the lung tissue was assessed by hematoxylin and eosin(HE),periodic acid–Schiff(PAS),and Van Gieson staining.ELISA was used to evaluate the IL-13,IL-25,and IL-33 in the mice.Western blotting was used to examine changes in the proteins levels of transient receptor potential vanilloid-1(TRPV1)and mucin 5AC(MUC5AC)in the lung tissues of mice.Results:Histopathological evaluation revealed that the OVA and OVA+RSV groups exhibited lung tissue edema and inflammatory lung tissue infiltration in the HE staining and airway secretions in the PAS staining;collagen hyperplasia around the airway was increased in these two groups compared with the control group.The QF group exhibited significantly reduced lung tissue edema,inflammatory lung tissue infiltration,airway secretions,and collagen hyperplasia around the airway compared with the OVA+RSV group.We analyzed the serum levels of IL-13,IL-25,and IL-33 in the mice and found that these levels were higher in the OVA and OVA+RSV groups than in the control group(P<0.05 in the OVA group,P<0.01 in the OVA+RSV group).The QF group exhibited significantly decreased serum levels of IL-13,IL-25,and IL-33 compared with the OVA+RSV group(all P<0.05).The Dxms group also exhibited significant decreases in the serum levels of IL-13 and IL-33(all P<0.05)but no significant decrease in the serum levels of IL-25 compared with the RSV+OVA group.Finally,we examined the protein levels of TRPV1 and MUC5AC in the lung tissues of mice using Western blotting.After identifying RSV infection in the mice with asthma,the protein levels of TRPV1 and MUC5AC in the lung tissues of mice were significantly higher than those in the control group(P<0.05,P<0.01).We found that compared with RSV+OVA,QF can significantly downregulate the protein level of TRPV1;further,the protein level of MUC5AC was also significantly reduced(all P<0.001).Conclusion:QF can inhibit RSV replication and reduce airway inflammation and mucus hypersecretion injury caused by RSV infection and asthma,and its mechanism of action may be associated with the downregulation of TRPV1 expression and a decrease in airway mucus hypersecretion injury.展开更多
In order to study the relationship between replicative status and human leucocyte antigens(HLA),HLA class Ⅱ antigen on hepatocyte membrane was analyzed in liver biopsies from 49 pa-tients with chronic hepatitis B vir...In order to study the relationship between replicative status and human leucocyte antigens(HLA),HLA class Ⅱ antigen on hepatocyte membrane was analyzed in liver biopsies from 49 pa-tients with chronic hepatitis B virus infection.The results revealed that expression of HLA classⅡ antigen on hepatocyte membrane was observed in 57% (13/23) of hepatitis B e antigen (HBeAg)positive,only in 15% (4/26) of anti-HBe positive carriers.The display of HLA class Ⅱ antigen onhepatocyte membrane yeas found in 65% (11/17) hepatitis B core antigen (HBcAg) positive and in19% (6/32) HBcAg negative patients with chronic hepatitis B virus infection.There was nosignificant difference in the expression of HLA class Ⅱ antigen on hepatocyte membrane between mi-nor hepatic diseases and active liver diseases.These findings suggested that display of HLA classⅡ antigen on hepatocyte membrane might be associated with viral replication in the chronic hepati-tis B virus carriers.展开更多
[Objective] The paper was to establish pyrosequencing methods for detecting viral hemorrhagic septicemia virus (VHSV). [ Method ] One pair of PCR primers and one pyrosequencing primer of VHSV were designed. The pyro...[Objective] The paper was to establish pyrosequencing methods for detecting viral hemorrhagic septicemia virus (VHSV). [ Method ] One pair of PCR primers and one pyrosequencing primer of VHSV were designed. The pyrosequencing reaction system and conditions were optimized and the pyrosequencing method for detecting VHSV was established. [ Result] This method was only able to specifically detect the objective viruses in the eight fish viruses, and the method had the advantage of high sensitivity. The minimum detectable limit of nucleic acid was 82 copies/μL. The method was verified by detecting VHSV in 1 924 batches of samples collected from domestic and imported fishes. The detection results were consistent with that of traditional RT-PCR, and the specificity and sensitivity of the method could meet the detection requirement for aquatic animal diseases. [ Conclusion] The study provides a new detection method for monitoring and prevention and control of aquatic animal virus diseases.展开更多
AIM:To investigate the early viral kinetics and interleukin-28B(IL28B)polymorphisms of hepatitis C genotype6 during pegylated interferon and ribavirin therapy.METHODS:Sixty-five patients with chronic hepatitis C virus...AIM:To investigate the early viral kinetics and interleukin-28B(IL28B)polymorphisms of hepatitis C genotype6 during pegylated interferon and ribavirin therapy.METHODS:Sixty-five patients with chronic hepatitis C virus(HCV)infection treated with pegylated interferon and ribavirin(PEG-IFN/RBV)were included,of whom15(23.1%),16(24.6%)and 34(52.3%)patients were infected with hepatitis C genotype 1(HCV-1),genotype3(HCV-3)and genotype 6(HCV-6),respectively.Serum HCV-RNA levels were measured frequently during the first 4-wk of therapy.DNA extracted from samples was analyzed for the IL28B single nucleotide polymorphism(SNP)rs12979860 by polymerase chain reaction and direct sequencing.RESULTS:During the first 4-wk of therapy,the mean viral decline for patients with HCV-6(5.55±1.82 log10IU/mL)was comparable to that of patients with HCV-3(5.55±1.82 log10IU/mL vs 5.86±1.02 log10IU/mL,P=0.44)and was significantly higher than patients with HCV-1(5.55±1.82 log10IU/mL vs 4.23±1.99 log10IU/mL,P=0.04).In the HCV-6 group,the first phase(days 0-2)viral decline was significantly higher in patients with the favorable rs12979860 CC than non-CC genotypes(2.46±1.01 log10IU/mL/wk vs 1.70±0.67 log10IU/mL,respectively,P=0.045).A statistically insignificant decrease in the second-phase(days 7-28)decline was also found in patients with the CC genotype than those with the non-CC genotype,though not significantly different(1.24±0.64 log10IU/mL/wk vs 0.80±0.65 log10IU/mL/wk,respectively,P=0.172).At baseline,the SNP genotype was an independent predictor of rapid virological response but not of sustained virological response.CONCLUSION:The IL28B genotype was linked to an impact on early viral kinetics in response to PEG-IFN/RBV therapy in HCV-6 infected patients.展开更多
Nipah Virus (NiV), a member of the Paramyxoviridae family, is one of the most infectious zoonotic viruses in Southeast Asia. First recorded in Malaysia in 1998, the NiV outbreak infected hundreds of people, with an al...Nipah Virus (NiV), a member of the Paramyxoviridae family, is one of the most infectious zoonotic viruses in Southeast Asia. First recorded in Malaysia in 1998, the NiV outbreak infected hundreds of people, with an almost 50% death rate. The virus is transmitted through direct contact with contaminated subjects and infecting the human respiratory system. Ephrin B2 and B3, the surface glycoproteins on the host cell, have been the primary and the most effective route for viral entrance. Binding with viral surface G protein, the F protein triggers, enabling viral-host fusion. Until now, NiV vaccines are not yet available in the public market, however, preventions such as avoiding direct contact and masking are advised.展开更多
Background:In the management of patients with MARV infection,this review article focuses on the potential protective effects of black seeds(Nigella sativa).Methods:To find studies that evaluated various effects of bla...Background:In the management of patients with MARV infection,this review article focuses on the potential protective effects of black seeds(Nigella sativa).Methods:To find studies that evaluated various effects of black seeds(N.sativa)related to signs and symptoms of MARV infection,reference lists and databases such as Medline/Pubmed/PMC,Google Scholar,Science Direct,Ebsco,Scopus,Web of Science,and Embase were searched.Results:In numerous clinical,animal,in-vitro,in-vivo,and in-ovo studies,black seeds(N.sativa)have demonstrated potential antiviral,anti-inflammatory,antioxidant,immunomodulatory,and hepatoprotective properties that may aid in the treatment of MARV-infected patients.Conclusion:In the initial generalization phase of MARV infection,patients may use black seeds(N.sativa)as an adjunctive therapy in addition to symptomatic treatment and supportive care.Future randomized controlled clinical trials would confirm N.sativa’s efficacy and safety in MARV-infected patients.展开更多
AIM: To evaluate the expression of fibrinogenlike protein 2 (fgl2) and its correlation with disease progression in both mice and patients with severe viral hepatitis.METHODS: Balb/cJ or A/J mice were infected intraper...AIM: To evaluate the expression of fibrinogenlike protein 2 (fgl2) and its correlation with disease progression in both mice and patients with severe viral hepatitis.METHODS: Balb/cJ or A/J mice were infected intraperitoneally (ip) with 100 PFU of murine hepatitis virus type 3 (MHV-3), liver and serum were harvested at 24, 48, and 72 h post infection for further use. Liver tissues were obtained from 23 patients with severe acute chronic (AOC) hepatitis B and 13 patients with mild chronic hepatitis B. Fourteen patients with mild chronic hepatitis B with cirrhosis and 4 liver donors served as normal controls. In addition, peripheral blood mononuclear cells (PBMC) were isolated from 30 patients (unpaired) with severe AOC hepatitis B and 10 healthy volunteers as controls. Procoagulant activity representing functional prothrombinaseactivity in PBMC and white blood cells was also assayed. A polyclonal antibody against fgl2 was used to detect the expression of both mouse and human fgl2 protein in liver samples as well as in PBMC by immunohistochemistry staining in a separate set of studies. Alanine aminotransferase (ALT) and total bilirubin (TBil) in serum were measured to assess the severity of liver injury.RESULTS: Histological changes were found in liver sections 12-24 h post MHV-3 infection in Balb/cJ mice.In association with changes in liver histology, marked elevations in serum ALT and TBil were observed. Mouse fgl2 (mfgl2) protein was detected in the endothelium of intrahepatic veins and hepatic sinusoids within the liver 24 h after MHV-3 infection. Liver tissues from the patients with severe AOC hepatitis B had classical pathological features of acute necroinflammation. Human fgl2 (hfgl2)was detected in 21 of 23 patients (91.30%)with severe AOC hepatitis B, while only 1 of 13 patients(7.69%) with mild chronic hepatitis B and cirrhosis had hfgl2 mRNA or protein expression. Twenty-eight of thirty patients (93.33%) with severe AOC hepatitis B and 1of 10 with mild chronic hepatitis B had detectable hfgl2expression in PBMC. No hfgl2 expression was found either in the liver tissue or in the PBMC from normal donors. There was a positive correlation between hfgl2expression and the severity of the liver disease as indicated by the levels of TBil. PCA significantly increased in PBMC in patients with severe AOC hepatitis B.CONCLUSION: The molecular and cellular results reported here in both mice and patients with severe viral hepatitis suggest that virus-induced hfgl2prothrombinase/fibroleukin expression and the coagulation activity associated with the encoded fgl2protein play a pivotal role in initiating severe hepatitis.The measurement of hfgl2/fibroleukin expression in PBMC may serve as a useful marker to monitor the severity of AOC hepatitis B and a target for therapeutic intervention.展开更多
Chemokines produced in the liver during hepatitis C virus(HCV) infection induce migration of activated T cells from the periphery to infected parenchyma.The milieu of chemokines secreted by infected hepatocytes is pre...Chemokines produced in the liver during hepatitis C virus(HCV) infection induce migration of activated T cells from the periphery to infected parenchyma.The milieu of chemokines secreted by infected hepatocytes is predominantly associated with the T-helper cell/Tc1 T cell(Th1/Tc1) response.These chemokines consist of CCL3(macrophage inflammatory protein-1α;MIP-1α),CCL4(MIP-1β),CCL5(regulated on activation normal T cell expressed and secreted;RANTES),CXCL10(interferon-γ-inducible protein-10;IP-10),CXCL11(interferon-inducible T-cell α chemoattractant;I-TAC),and CXCL9(monokine induced by interferon γ;Mig) and they recruit T cells expressing either CCR5 or CXCR3 chemokine receptors.Intrahepatic and peripheral blood levels of these chemokines are increased during chronic hepatitis C.The interaction between chemokines and their receptors is essential in recruiting HCV-specific T cells to control the infection.When the adaptive immune response fails in this task,non-specific T cells without the capacity to control the infection are also recruited to the liver,and these are ultimately responsible for the persistent hepatic damage.The modulation of chemokine receptor expression and chemokine secretion could be a viral escape mechanism to avoid specific T cell migration to the liver during the early phase of infection,and to maintain liver viability during the chronic phase,by impairing non-specific T cell migration.Some chemokines and their receptors correlate with liver damage,and CXCL10(IP-10) and CXCR3 levels have shown a clinical utility as predictors of treatment response outcome.The regulation of chemokines and their receptors could be a future potential therapeutic target to decrease liver inflammation and to increase specific T cell migration to the infected liver.展开更多
AIM: To achieve a better understanding of the pathogenesis of new type gosling viral enteritis virus (NGVEV) and the relationship between NGVEV and host cells. METHODS: The apoptosis of duck embryo fibroblasts (DEF) i...AIM: To achieve a better understanding of the pathogenesis of new type gosling viral enteritis virus (NGVEV) and the relationship between NGVEV and host cells. METHODS: The apoptosis of duck embryo fibroblasts (DEF) induced by NGVEV was investigated by fluorescence-activated cell sorter (FACS) and fluorescence microscope after the cells were stained with Annexin V-FITC and propidium iodide (PI). RESULTS: By staining cells with a combination of fluorescein annexin V-FITC and PI, it is possible to distinguish and quantitatively analyze non-apoptotic cells (Annexin V-FITC negative/PI negative), early apoptotic cells (Annexin V-FITC positive/PI negative), late apoptotic/necrotic cells (Annexin V-FITC positive/ PI positive) and dead cells (Annexin V-FITC negative/PI positive) through flow cytometry and fluorescence microscope. The percentage of apoptotic cells increased with the incubation time and reached a maximum at 120 h after infection, while the percentage of non- apoptotic cells decreased.展开更多
AIM: To elucidate risk factors contributing to the development of hepatocellular carcinoma (HCC) among patients with sustained viral response (SVR) after interferon (IFN) treatment and to examine whether HCV-RNA still...AIM: To elucidate risk factors contributing to the development of hepatocellular carcinoma (HCC) among patients with sustained viral response (SVR) after interferon (IFN) treatment and to examine whether HCV-RNA still remained in the liver of SVR patients who developed HCC. METHODS: Two-hundred and sixty-six patients, who achieved SVR, were enrolled in this study. We retrospectively reviewed clinical, viral and histological features of the patients, and examined whether the development of HCC depends on several clinical variables using Kaplan-Meier Method. RT-PCR was used to seek HCV-RNA in 3 out of 7 patients in whom liver tissue was available for molecular analysis. RESULTS: Among the enrolled 266 patients with SVR, HCC developed in 7 patients (7/266; 2.6%). We failed to detect HCV-RNA both in cancer and non-cancerous liver tissue in all three patients. The cumulative incidence for HCC was significantly different depending on hepatic fibrosis (F3-4) (P = 0.0028), hepatic steatosis (Grade 2-3) (P = 0.0002) and age (≥ 55) (P = 0.021) at the pre-interferon treatment. CONCLUSION: The current study demonstrated that age, hepatic fibrosis, and hepatic steatosis at pre- interferon treatment might be risk factors for developing HCC after SVR.展开更多
AIM:To identify the prevalence of hepatitis B e antigen (HBeAg) and to assess the association of hepatitis B virus (HBV) core promoter mutations and viral load in Indonesian patients.METHODS:Sixty-four patients with c...AIM:To identify the prevalence of hepatitis B e antigen (HBeAg) and to assess the association of hepatitis B virus (HBV) core promoter mutations and viral load in Indonesian patients.METHODS:Sixty-four patients with chronic hepatitis,65 with liver cirrhosis and 50 with hepatocellular carcinoma were included in this study.HBeAg and hepatitis B e antibody (HBeAb) tests were performed using enzyme-linked immunosorbent assay and the mutations were analyzed by sequencing.Viral load was measured by real-time polymerase chain reaction.RESULTS:Of 179 patients,108 (60.3%) were HBeAg(-) and 86 (79.6%) of these HBeAg(-) patients had been seroconverted.The A1896 mutation was not found in HBeAg(+) patients,however,this mutation was detected in 70.7% of HBeAg(-) patients.This mutation was frequently found when HBeAg was not expressed (87.7%),compared to that found in HBeAg seroconverted patients (65.1%).The A1899 mutation was also more prevalent in HBeAg(-) than in HBeAg(+) patients (P=0.004).The T1762/A1764 mutation was frequently found in both HBeAg(+) and HBeAg(-) patients,however,the prevalence of this mutation did not significantly differ among the two groups (P=0.054).In HBeAg(+) patients,the T1762/A1764 mutation was correlated with lower HBV DNA (P < 0.001).The A1899 mutation did not correlate with HBV DNA (P=0.609).In HBeAg(-) patients,the T1762/A1764 mutation alone was not correlated with HBV DNA (P=0.095),however,the presence of either the T1762/A1764 or A1896 mutations was associated with increased HBV DNA (P < 0.001).CONCLUSION:The percentage of HBeAg(-) patients is high in Indonesia,and most of the HBeAg(-) patients had been seroconverted.The A1896 mutation was most likely the major cause of HBeAg loss.The T1762/A1764 mutation alone was associated with lower viral loads in HBeAg(+) patients,but not in HBeAg(-) patients.展开更多
Viral infections have been considered as a major cause of morbidity and mortality after kidney transplantation in pediatric cohort.Children are at high risk of acquiring virus-related complications due to immunologica...Viral infections have been considered as a major cause of morbidity and mortality after kidney transplantation in pediatric cohort.Children are at high risk of acquiring virus-related complications due to immunological immaturity and the enhanced alloreactivity risk that led to maintenance of high immunosuppressive regimes.Hence,prevention,early detection,and prompt treatment of such infections are of paramount importance.Among all viral infections,herpes viruses(herpes simplex virus,varicella zoster virus,Epstein-Barr virus,cytomegalovirus),hepatitis B and C viruses,BK polyomavirus,and respiratory viruses(respiratory syncytial virus,parainfluenza virus,influenza virus and adenovirus)are common in kidney transplant recipients.These viruses can cause systemic disease or allograft dysfunction affecting the clinical outcome.Recent advances in technology and antiviral therapy have improved management strategies in screening,monitoring,adoption of prophylactic or preemptive therapy and precise treatment in the immunocompromised host,with significant impact on the outcome.This review discusses the etiology,screening and monitoring,diagnosis,prevention,and treatment of common viral infections in pediatric renal transplant recipients.展开更多
文摘Autism spectrum disorder(ASD)is a group of heterogeneous,multi-factorial,neurodevelopmental disorders resulting from genetic and environmental factors interplay.Infection is a significant trigger of autism,especially during the critical developmental period.There is a strong interplay between the viral infection as a trigger and a result of ASD.We aim to highlight the mutual relationship between autism and viruses.We performed a thorough literature review and included 158 research in this review.Most of the literature agreed on the possible effects of the viral infection during the critical period of development on the risk of developing autism,especially for specific viral infections such as Rubella,Cytomegalovirus,Herpes Simplex virus,Varicella Zoster Virus,Influenza virus,Zika virus,and severe acute respiratory syndrome coronavirus 2.Viral infection directly infects the brain,triggers immune activation,induces epigenetic changes,and raises the risks of having a child with autism.At the same time,there is some evidence of increased risk of infection,including viral infections in children with autism,due to lots of factors.There is an increased risk of developing autism with a specific viral infection during the early developmental period and an increased risk of viral infections in children with autism.In addition,children with autism are at increased risk of infection,including viruses.Every effort should be made to prevent maternal and early-life infections and reduce the risk of autism.Immune modulation of children with autism should be considered to reduce the risk of infection.
基金Supported by The DFG,SFB638,TP A5 and SFB/TRR83,TP 13
文摘Plus-strand RNA virus replication occurs in tight association with cytoplasmic host cell membranes. Both, viral and cellular factors cooperatively generate distinct organelle-like structures, designated viral replication factories. This compartmentalization allows coordination of the different steps of the viral replication cycle, highly efficient genome replication and protection of the viral RNA from cellular defense mechanisms. Electron tomography studies conducted during the last couple of years revealed the three dimensional structure of numerous plus-strand RNA virus replication compartments and highlight morphological analogies between different virus families. Based on the morphology of virusinduced membrane rearrangements, we propose two separate subclasses: the invaginated vesicle/spherule type and the double membrane vesicle type. This review discusses common themes and distinct differences in the architecture of plus-strand RNA virus-induced membrane alterations and summarizes recent progress that has been made in understanding the complex interplay between viral and co-opted cellular factors in biogenesis and maintenance of plus-strand RNA virus replication factories.
基金Supported by The Harry Crossley Postdoctoral Research Fellowship 2021.
文摘Elimination of viral hepatitis in sub-Saharan Africa by 2030 is an ambitious feat.However,as stated by the World Health Organization,there are unprecedented opportunities to act and make significant contributions to the elimination target.With 60 million people chronically infected with hepatitis B virus(HBV)of whom 38800 are at risk of developing highly fatal hepatocellular carcinoma(HCC)every year,sub-Saharan Africa faces one of the greatest battles towards elimination of viral hepatitis.There is a need to examine progress in controlling the disproportionate burden of HBV-associated HCC in sub-Saharan Africa within the context of this elimination target.By scaling-up coverage of hepatitis B birth dose and early childhood vaccination,we can significantly reduce new cases of HCC by as much as 50%within the next three to five decades.Given the substantial reservoir of chronic HBV carriers however,projections show that HCC incidence and mortality rates in sub-Saharan Africa will double by 2040.This warrants urgent public health attention.The trends in the burden of HCC over the next two decades,will be determined to a large extent by progress in achieving early diagnosis and appropriate linkage to care for high-risk chronic HBV infected persons.
文摘Hepatitis C virus(HCV)infection is the leading cause of chronic liver-related diseases,including cirrhosis,liver failure,and hepatocellular carcinoma.Currently,no effective vaccine is available for HCV infection.Polyethylene glycol interferon-α(PegIFN-α)in combination with ribavirin(RBV)is the standard of care(SOC)for chronic hepatitis C.However,the efficacy of PegIFN-αand RBV combination therapy is less than 50%for genotype 1HCV,which is the dominant virus in humans.In addition,IFN and RBV have several severe side effects.Therefore,strategies to improve sustained virological response(SVR)rates have been an important focus for clinical physicians.The serine protease inhibitors telaprevir and boceprevir were approved by the United States Food and Drug Administration in 2011.The addition of HCV protease inhibitors to the SOC has significantly improved the efficacy of treatments for HCV infection.Several direct-acting antiviral drugs currently in late-stage clinical trials,both with and without pegIFN and RBV,have several advantages over the previous SOC,including higher specificity and efficacy,fewer side effects,and the ability to be administered orally,and might be optimal regimens in the future.Factors affecting the efficacy of anti-HCV treatments based on IFN-αinclude the HCV genotype,baseline viral load,virological response during treatment,host IL28B gene polymorphisms and hepatic steatosis.However,determining the effect of the above factors on DAA therapy is necessary.In this review,we summarize the development of antiHCV agents and assess the main factors affecting the efficacy of antiviral treatments.
基金supported by the grants from the National Natural Science Foundation of China(31072157)the National Key Technologies R&D Program of China during the 12th Five-Year Plan period(2015BAD12B05)+1 种基金the Foundation of China Agricultural Research System(CARS-43-8)the Major Project of Education Department in Sichuan,China(16ZA0027)
文摘Many mammalian herpes viruses utilize heparan sulfate (HS) moieties present on cell surface proteoglycans as receptors for cell entry, and this process also requires viral glycoprotein C (gC) homologues. However, our understanding of the role of gC in facilitating attachment of other alpha-herpes viruses such as the duck plague virus (DPV) remains preliminary. To study the role of gC during DPV infection, we used a gC-deleted mutant virus (DPV-AgC-EGFP). Examination of the viral copy number by real-time PCR, as well as time course studies of viral adsorption and proliferation revealed that gC was involved in the viral binding to the cell surface. The affinity of viral glycoproteins (gB-DPV, gC-DPV, and gE-DPV) to HS was assessed using a prokaryotic expression system and HJTrapTM HeparJn HP column chromatography. In addition, to confirm that gC played a role in the interaction between DPV and HS, viruses were treated with the HS analogue heparin and host cells were treated with its inhibitors heparinase prior to exposure to DPV-△gC-EGFP or wild-type strain Chinese virulent duck plague virus (DPV-CHv). The effects of heparin and heparinase on virus infectivity demonstrated that function of gC on Viral adsorption is independent of interactions between gC and heparin sulfate on cell surface. All in all, this study demonstrated that the gC of DPV can mediate viral adsorption in an HS-independent manner, which distinguish it from the gC of some other alpha-herpes viruses. Future studies will be required to identify the receptors involved in gC protein binding to cells. This work provides us a foundation for further studies of examining the roles of gC in the adsorption during duck plague virus infection.
文摘Bluetongue (BT) is a serious hemorrhagic disease of ruminants caused by bluetongue virus (BTV). Inactive BTV vaccines have been successful in field trials in some areas, and inactivated vaccines are considered safer. However, information about the effect of the viral antigen level on the serological response and efficiency of the inactive BTV-16 vaccine is lacking. In the present study, the serological response and efficiency of the viral antigen concentration in the binary ethylenimine-inactivated Chinese BTV serotype-16 vaccine were investigated. The viral antigens in the viral suspension (VS) were quantified using a modified BTV AC-ELISA method. Four batches of vaccine containing 1, 5, 10, and 50 μg/ml of viral antigen were generated from the VS. Four groups of naive Chinese sheep were vaccinated with the different vaccine batches, and the serological response and vaccine efficiency were investigated before and after challenge infection. The vaccines containing 10 and 50 μg/ml of viral antigen induced significant ELISA and neutralizing antibody titers 14 days after vaccination, whereas the vaccines containing 1 and 5 μg/ml of viral antigen did not have these effects. A booster immunization at 21 days enhanced all groups’ antibody titers;however, the increased titer was related to the viral antigen level. In contrast to the serological response, the viral antigen level of the vaccines did not have a significant effect on the vaccine efficiency. With the exception of one sheep from the 5 μg/ml viral antigen group, all vaccinated sheep from the four antigen level groups showed strong resistance to infection based on their clinical symptoms, rectal temperatures and viremia. Collectively, these data suggested that viral antigen levels from 1 to 50 μg/ml had a significant effect on the serological response of the animals but a limited effect on the vaccine efficiency. The BTV-16 vaccine containing 1 μg/ml of viral antigen was sufficient to achieve high efficiency, but only the vaccines with more than 10 μg/ml of antigen induced a significant antibody response. To obtain a better serological response, we suggest the use of vaccines with more than 10 μg/ml of viral antigen. The findings in the study will be useful for BTV vaccine production.
基金This work was supported by Natural Science Foundation of China(81674020).
文摘Objective:Qingfei oral liquid(QF),an experimental Chinese medicine prescription developed from the ancient priscription of traditional Chinese medicines Ma Xin Shi Gan decoction and Tingli Dazao Xie Fei decoction,has been effectively used since decades to treat patients with viral pneumonia and asthma.In our previous study,we had demonstrated that QF can significantly reduce airway hyperresponsiveness,hyperemia,lung tissue edema,inflammatory lung tissue infiltration in mice,airway mucus secretion,and peripheral airway collagen hyperplasia;however,its mechanism of action is unknown.Methods:Fifty 6–8-week-old male BALB/c mice were equally and randomly divided into five groups:the control,ovalbumin(OVA),OVA+respiratory syncytial virus(RSV),QF,and dexamethasone(Dxms)groups.The QF group was administered QF at 1.17 g·kg−1·d−1,the Dxms group received dexamethasone injections at 0.2 mg·kg−1·d−1,and the remaining groups were administered PBS.Inflammation in the lung tissue was assessed by hematoxylin and eosin(HE),periodic acid–Schiff(PAS),and Van Gieson staining.ELISA was used to evaluate the IL-13,IL-25,and IL-33 in the mice.Western blotting was used to examine changes in the proteins levels of transient receptor potential vanilloid-1(TRPV1)and mucin 5AC(MUC5AC)in the lung tissues of mice.Results:Histopathological evaluation revealed that the OVA and OVA+RSV groups exhibited lung tissue edema and inflammatory lung tissue infiltration in the HE staining and airway secretions in the PAS staining;collagen hyperplasia around the airway was increased in these two groups compared with the control group.The QF group exhibited significantly reduced lung tissue edema,inflammatory lung tissue infiltration,airway secretions,and collagen hyperplasia around the airway compared with the OVA+RSV group.We analyzed the serum levels of IL-13,IL-25,and IL-33 in the mice and found that these levels were higher in the OVA and OVA+RSV groups than in the control group(P<0.05 in the OVA group,P<0.01 in the OVA+RSV group).The QF group exhibited significantly decreased serum levels of IL-13,IL-25,and IL-33 compared with the OVA+RSV group(all P<0.05).The Dxms group also exhibited significant decreases in the serum levels of IL-13 and IL-33(all P<0.05)but no significant decrease in the serum levels of IL-25 compared with the RSV+OVA group.Finally,we examined the protein levels of TRPV1 and MUC5AC in the lung tissues of mice using Western blotting.After identifying RSV infection in the mice with asthma,the protein levels of TRPV1 and MUC5AC in the lung tissues of mice were significantly higher than those in the control group(P<0.05,P<0.01).We found that compared with RSV+OVA,QF can significantly downregulate the protein level of TRPV1;further,the protein level of MUC5AC was also significantly reduced(all P<0.001).Conclusion:QF can inhibit RSV replication and reduce airway inflammation and mucus hypersecretion injury caused by RSV infection and asthma,and its mechanism of action may be associated with the downregulation of TRPV1 expression and a decrease in airway mucus hypersecretion injury.
文摘In order to study the relationship between replicative status and human leucocyte antigens(HLA),HLA class Ⅱ antigen on hepatocyte membrane was analyzed in liver biopsies from 49 pa-tients with chronic hepatitis B virus infection.The results revealed that expression of HLA classⅡ antigen on hepatocyte membrane was observed in 57% (13/23) of hepatitis B e antigen (HBeAg)positive,only in 15% (4/26) of anti-HBe positive carriers.The display of HLA class Ⅱ antigen onhepatocyte membrane yeas found in 65% (11/17) hepatitis B core antigen (HBcAg) positive and in19% (6/32) HBcAg negative patients with chronic hepatitis B virus infection.There was nosignificant difference in the expression of HLA class Ⅱ antigen on hepatocyte membrane between mi-nor hepatic diseases and active liver diseases.These findings suggested that display of HLA classⅡ antigen on hepatocyte membrane might be associated with viral replication in the chronic hepati-tis B virus carriers.
基金Supported by the Twelfth Five-Year Support Project of the Ministry of Science and Technology(2013BAD12B02)Science and Technology Project of State General Administration of the People’s Republic of China for Quality Supervision and Inspection and Quarantine(2015IK195)
文摘[Objective] The paper was to establish pyrosequencing methods for detecting viral hemorrhagic septicemia virus (VHSV). [ Method ] One pair of PCR primers and one pyrosequencing primer of VHSV were designed. The pyrosequencing reaction system and conditions were optimized and the pyrosequencing method for detecting VHSV was established. [ Result] This method was only able to specifically detect the objective viruses in the eight fish viruses, and the method had the advantage of high sensitivity. The minimum detectable limit of nucleic acid was 82 copies/μL. The method was verified by detecting VHSV in 1 924 batches of samples collected from domestic and imported fishes. The detection results were consistent with that of traditional RT-PCR, and the specificity and sensitivity of the method could meet the detection requirement for aquatic animal diseases. [ Conclusion] The study provides a new detection method for monitoring and prevention and control of aquatic animal virus diseases.
基金Supported by Chulalongkorn University,No.RES560530155Thailand Research Fund,No.BRG5580005,and No.DPG5480002+2 种基金Joint Research Program between National Research Council of Thailand and Japan Society for the Promotion of Science,Centenary Academic Development Project,No.CU56-HR01Ratchadapiseksompotch Fund(Faculty of Medicine),Integrated Innovation Academic Center and Postdoctoral of Ratchadaphiseksomphot Endowment Fund,Chulalongkorn UniversityHigher Education Research Promotion and National Research University Project of Thailand,Office of the Higher Education Commission,No.HR1155A
文摘AIM:To investigate the early viral kinetics and interleukin-28B(IL28B)polymorphisms of hepatitis C genotype6 during pegylated interferon and ribavirin therapy.METHODS:Sixty-five patients with chronic hepatitis C virus(HCV)infection treated with pegylated interferon and ribavirin(PEG-IFN/RBV)were included,of whom15(23.1%),16(24.6%)and 34(52.3%)patients were infected with hepatitis C genotype 1(HCV-1),genotype3(HCV-3)and genotype 6(HCV-6),respectively.Serum HCV-RNA levels were measured frequently during the first 4-wk of therapy.DNA extracted from samples was analyzed for the IL28B single nucleotide polymorphism(SNP)rs12979860 by polymerase chain reaction and direct sequencing.RESULTS:During the first 4-wk of therapy,the mean viral decline for patients with HCV-6(5.55±1.82 log10IU/mL)was comparable to that of patients with HCV-3(5.55±1.82 log10IU/mL vs 5.86±1.02 log10IU/mL,P=0.44)and was significantly higher than patients with HCV-1(5.55±1.82 log10IU/mL vs 4.23±1.99 log10IU/mL,P=0.04).In the HCV-6 group,the first phase(days 0-2)viral decline was significantly higher in patients with the favorable rs12979860 CC than non-CC genotypes(2.46±1.01 log10IU/mL/wk vs 1.70±0.67 log10IU/mL,respectively,P=0.045).A statistically insignificant decrease in the second-phase(days 7-28)decline was also found in patients with the CC genotype than those with the non-CC genotype,though not significantly different(1.24±0.64 log10IU/mL/wk vs 0.80±0.65 log10IU/mL/wk,respectively,P=0.172).At baseline,the SNP genotype was an independent predictor of rapid virological response but not of sustained virological response.CONCLUSION:The IL28B genotype was linked to an impact on early viral kinetics in response to PEG-IFN/RBV therapy in HCV-6 infected patients.
文摘Nipah Virus (NiV), a member of the Paramyxoviridae family, is one of the most infectious zoonotic viruses in Southeast Asia. First recorded in Malaysia in 1998, the NiV outbreak infected hundreds of people, with an almost 50% death rate. The virus is transmitted through direct contact with contaminated subjects and infecting the human respiratory system. Ephrin B2 and B3, the surface glycoproteins on the host cell, have been the primary and the most effective route for viral entrance. Binding with viral surface G protein, the F protein triggers, enabling viral-host fusion. Until now, NiV vaccines are not yet available in the public market, however, preventions such as avoiding direct contact and masking are advised.
文摘Background:In the management of patients with MARV infection,this review article focuses on the potential protective effects of black seeds(Nigella sativa).Methods:To find studies that evaluated various effects of black seeds(N.sativa)related to signs and symptoms of MARV infection,reference lists and databases such as Medline/Pubmed/PMC,Google Scholar,Science Direct,Ebsco,Scopus,Web of Science,and Embase were searched.Results:In numerous clinical,animal,in-vitro,in-vivo,and in-ovo studies,black seeds(N.sativa)have demonstrated potential antiviral,anti-inflammatory,antioxidant,immunomodulatory,and hepatoprotective properties that may aid in the treatment of MARV-infected patients.Conclusion:In the initial generalization phase of MARV infection,patients may use black seeds(N.sativa)as an adjunctive therapy in addition to symptomatic treatment and supportive care.Future randomized controlled clinical trials would confirm N.sativa’s efficacy and safety in MARV-infected patients.
基金Supported by the National Natural Science Foundation of China for Distinguished Young Scholars, No. 30225040 for Dr Ning Q,No. 30123019 for Dr Luo XP
文摘AIM: To evaluate the expression of fibrinogenlike protein 2 (fgl2) and its correlation with disease progression in both mice and patients with severe viral hepatitis.METHODS: Balb/cJ or A/J mice were infected intraperitoneally (ip) with 100 PFU of murine hepatitis virus type 3 (MHV-3), liver and serum were harvested at 24, 48, and 72 h post infection for further use. Liver tissues were obtained from 23 patients with severe acute chronic (AOC) hepatitis B and 13 patients with mild chronic hepatitis B. Fourteen patients with mild chronic hepatitis B with cirrhosis and 4 liver donors served as normal controls. In addition, peripheral blood mononuclear cells (PBMC) were isolated from 30 patients (unpaired) with severe AOC hepatitis B and 10 healthy volunteers as controls. Procoagulant activity representing functional prothrombinaseactivity in PBMC and white blood cells was also assayed. A polyclonal antibody against fgl2 was used to detect the expression of both mouse and human fgl2 protein in liver samples as well as in PBMC by immunohistochemistry staining in a separate set of studies. Alanine aminotransferase (ALT) and total bilirubin (TBil) in serum were measured to assess the severity of liver injury.RESULTS: Histological changes were found in liver sections 12-24 h post MHV-3 infection in Balb/cJ mice.In association with changes in liver histology, marked elevations in serum ALT and TBil were observed. Mouse fgl2 (mfgl2) protein was detected in the endothelium of intrahepatic veins and hepatic sinusoids within the liver 24 h after MHV-3 infection. Liver tissues from the patients with severe AOC hepatitis B had classical pathological features of acute necroinflammation. Human fgl2 (hfgl2)was detected in 21 of 23 patients (91.30%)with severe AOC hepatitis B, while only 1 of 13 patients(7.69%) with mild chronic hepatitis B and cirrhosis had hfgl2 mRNA or protein expression. Twenty-eight of thirty patients (93.33%) with severe AOC hepatitis B and 1of 10 with mild chronic hepatitis B had detectable hfgl2expression in PBMC. No hfgl2 expression was found either in the liver tissue or in the PBMC from normal donors. There was a positive correlation between hfgl2expression and the severity of the liver disease as indicated by the levels of TBil. PCA significantly increased in PBMC in patients with severe AOC hepatitis B.CONCLUSION: The molecular and cellular results reported here in both mice and patients with severe viral hepatitis suggest that virus-induced hfgl2prothrombinase/fibroleukin expression and the coagulation activity associated with the encoded fgl2protein play a pivotal role in initiating severe hepatitis.The measurement of hfgl2/fibroleukin expression in PBMC may serve as a useful marker to monitor the severity of AOC hepatitis B and a target for therapeutic intervention.
基金Supported by Grants from "Fiscam" J.C.C.M (Ayuda paraproyectos de investigación en saludPI-2007/32)+7 种基金"AsociaciónCastellana de Aparato Digestivo" (Beca ACADACAD/06)"Fundación de Investigación Médica Mutua Madrilea"(Beca Ayudas a la Investigación FMMM2548/2008),Spainsupported by a research grantfrom "Fiscam" J.C.C.M ("Perfeccionamiento y movilidad deinvestigadores" MOV-2007_JI/18), Spainsupported by a research grant from "Instituto de SaludCarlos Ⅲ" (Contrato de apoyo a la investigación en el SNS"CA07/00157),Spain
文摘Chemokines produced in the liver during hepatitis C virus(HCV) infection induce migration of activated T cells from the periphery to infected parenchyma.The milieu of chemokines secreted by infected hepatocytes is predominantly associated with the T-helper cell/Tc1 T cell(Th1/Tc1) response.These chemokines consist of CCL3(macrophage inflammatory protein-1α;MIP-1α),CCL4(MIP-1β),CCL5(regulated on activation normal T cell expressed and secreted;RANTES),CXCL10(interferon-γ-inducible protein-10;IP-10),CXCL11(interferon-inducible T-cell α chemoattractant;I-TAC),and CXCL9(monokine induced by interferon γ;Mig) and they recruit T cells expressing either CCR5 or CXCR3 chemokine receptors.Intrahepatic and peripheral blood levels of these chemokines are increased during chronic hepatitis C.The interaction between chemokines and their receptors is essential in recruiting HCV-specific T cells to control the infection.When the adaptive immune response fails in this task,non-specific T cells without the capacity to control the infection are also recruited to the liver,and these are ultimately responsible for the persistent hepatic damage.The modulation of chemokine receptor expression and chemokine secretion could be a viral escape mechanism to avoid specific T cell migration to the liver during the early phase of infection,and to maintain liver viability during the chronic phase,by impairing non-specific T cell migration.Some chemokines and their receptors correlate with liver damage,and CXCL10(IP-10) and CXCR3 levels have shown a clinical utility as predictors of treatment response outcome.The regulation of chemokines and their receptors could be a future potential therapeutic target to decrease liver inflammation and to increase specific T cell migration to the infected liver.
基金The National Natural Science Foundation of China, No. 39970561The Key Projects in the National Science and Technology Pillar Program, 2007Z06-017+2 种基金Program for New Century Excellent Talents from Universities, Chinese Ministry of Education, No. NCET-04-0906/NCET-06-0818Fund of the Discipline Leaders of Sichuan Province, No. SZD0418Culture Fund for Excellent Doctoral Dissertations of Sichuan Agricultural University, 2008scybpy-1
文摘AIM: To achieve a better understanding of the pathogenesis of new type gosling viral enteritis virus (NGVEV) and the relationship between NGVEV and host cells. METHODS: The apoptosis of duck embryo fibroblasts (DEF) induced by NGVEV was investigated by fluorescence-activated cell sorter (FACS) and fluorescence microscope after the cells were stained with Annexin V-FITC and propidium iodide (PI). RESULTS: By staining cells with a combination of fluorescein annexin V-FITC and PI, it is possible to distinguish and quantitatively analyze non-apoptotic cells (Annexin V-FITC negative/PI negative), early apoptotic cells (Annexin V-FITC positive/PI negative), late apoptotic/necrotic cells (Annexin V-FITC positive/ PI positive) and dead cells (Annexin V-FITC negative/PI positive) through flow cytometry and fluorescence microscope. The percentage of apoptotic cells increased with the incubation time and reached a maximum at 120 h after infection, while the percentage of non- apoptotic cells decreased.
文摘AIM: To elucidate risk factors contributing to the development of hepatocellular carcinoma (HCC) among patients with sustained viral response (SVR) after interferon (IFN) treatment and to examine whether HCV-RNA still remained in the liver of SVR patients who developed HCC. METHODS: Two-hundred and sixty-six patients, who achieved SVR, were enrolled in this study. We retrospectively reviewed clinical, viral and histological features of the patients, and examined whether the development of HCC depends on several clinical variables using Kaplan-Meier Method. RT-PCR was used to seek HCV-RNA in 3 out of 7 patients in whom liver tissue was available for molecular analysis. RESULTS: Among the enrolled 266 patients with SVR, HCC developed in 7 patients (7/266; 2.6%). We failed to detect HCV-RNA both in cancer and non-cancerous liver tissue in all three patients. The cumulative incidence for HCC was significantly different depending on hepatic fibrosis (F3-4) (P = 0.0028), hepatic steatosis (Grade 2-3) (P = 0.0002) and age (≥ 55) (P = 0.021) at the pre-interferon treatment. CONCLUSION: The current study demonstrated that age, hepatic fibrosis, and hepatic steatosis at pre- interferon treatment might be risk factors for developing HCC after SVR.
基金Supported by MRIN Funding (Budget No.cc041/2009)
文摘AIM:To identify the prevalence of hepatitis B e antigen (HBeAg) and to assess the association of hepatitis B virus (HBV) core promoter mutations and viral load in Indonesian patients.METHODS:Sixty-four patients with chronic hepatitis,65 with liver cirrhosis and 50 with hepatocellular carcinoma were included in this study.HBeAg and hepatitis B e antibody (HBeAb) tests were performed using enzyme-linked immunosorbent assay and the mutations were analyzed by sequencing.Viral load was measured by real-time polymerase chain reaction.RESULTS:Of 179 patients,108 (60.3%) were HBeAg(-) and 86 (79.6%) of these HBeAg(-) patients had been seroconverted.The A1896 mutation was not found in HBeAg(+) patients,however,this mutation was detected in 70.7% of HBeAg(-) patients.This mutation was frequently found when HBeAg was not expressed (87.7%),compared to that found in HBeAg seroconverted patients (65.1%).The A1899 mutation was also more prevalent in HBeAg(-) than in HBeAg(+) patients (P=0.004).The T1762/A1764 mutation was frequently found in both HBeAg(+) and HBeAg(-) patients,however,the prevalence of this mutation did not significantly differ among the two groups (P=0.054).In HBeAg(+) patients,the T1762/A1764 mutation was correlated with lower HBV DNA (P < 0.001).The A1899 mutation did not correlate with HBV DNA (P=0.609).In HBeAg(-) patients,the T1762/A1764 mutation alone was not correlated with HBV DNA (P=0.095),however,the presence of either the T1762/A1764 or A1896 mutations was associated with increased HBV DNA (P < 0.001).CONCLUSION:The percentage of HBeAg(-) patients is high in Indonesia,and most of the HBeAg(-) patients had been seroconverted.The A1896 mutation was most likely the major cause of HBeAg loss.The T1762/A1764 mutation alone was associated with lower viral loads in HBeAg(+) patients,but not in HBeAg(-) patients.
文摘Viral infections have been considered as a major cause of morbidity and mortality after kidney transplantation in pediatric cohort.Children are at high risk of acquiring virus-related complications due to immunological immaturity and the enhanced alloreactivity risk that led to maintenance of high immunosuppressive regimes.Hence,prevention,early detection,and prompt treatment of such infections are of paramount importance.Among all viral infections,herpes viruses(herpes simplex virus,varicella zoster virus,Epstein-Barr virus,cytomegalovirus),hepatitis B and C viruses,BK polyomavirus,and respiratory viruses(respiratory syncytial virus,parainfluenza virus,influenza virus and adenovirus)are common in kidney transplant recipients.These viruses can cause systemic disease or allograft dysfunction affecting the clinical outcome.Recent advances in technology and antiviral therapy have improved management strategies in screening,monitoring,adoption of prophylactic or preemptive therapy and precise treatment in the immunocompromised host,with significant impact on the outcome.This review discusses the etiology,screening and monitoring,diagnosis,prevention,and treatment of common viral infections in pediatric renal transplant recipients.