BACKGROUND The co-occurrence of Anti-phospholipase A2 receptor-associated membranous nephropathy(anti-PLA2R-MN)and human immunodeficiency virus(HIV)infection is a rare clinical scenario,presenting significant challeng...BACKGROUND The co-occurrence of Anti-phospholipase A2 receptor-associated membranous nephropathy(anti-PLA2R-MN)and human immunodeficiency virus(HIV)infection is a rare clinical scenario,presenting significant challenges in terms of management and treatment.CASE SUMMARY A 32-year-old Chinese male diagnosed with HIV infection presented with a clinical history of proteinuria persisting for over two years.A kidney biopsy demonstrated subepithelial immune complex deposition and a thickened glomerular basement membrane,indicative of stage I-II membranous nephro-pathy.Immunofluorescence staining revealed granular deposition of PLA2R(3+)along the glomerular capillary loops,corroborated by a strongly positive anti-PLA2R antibody test(1:320).Initial treatment involving losartan potassium,rivaroxaban,tacrolimus,and rituximab was discontinued due to either poor effec-tiveness or the occurrence of adverse events.Following a regimen of weekly subcutaneous injections of telitacicept(160 mg),a marked decline in the 24 h urine protein was observed within a three-month period,accompanied by a rise in serum albumin level.No significant reductions in peripheral blood CD3+CD4+T and CD3+CD8+T cell counts were detected.The patient's physical and psychological conditions showed significant improvements,with no adverse events reported during the treatment course.CONCLUSION Telitacicept might offer a potential therapeutic avenue for patients diagnosed with anti-PLA2R-MN concomitant with HIV infection.展开更多
The possibility of infection of the human male genital tract by human herpes virus type 2 (HSV2) or human cytomegalovirus (HCMV) is well established and their sexual transmission has been the object of many studies. M...The possibility of infection of the human male genital tract by human herpes virus type 2 (HSV2) or human cytomegalovirus (HCMV) is well established and their sexual transmission has been the object of many studies. Moreover, medically assisted procreation, which helps in numerous fertility problems, raises the question of new viral risks linked to the application of these new technologies. In this review, we shall consider current knowledge in terms of the presence of HSV 2 and HCMV in the different parts of the genital tract of immunocompetent or immunodepressed men. We shall also consider the possibility of viral transmission by the sexual act or by the various techniques used in medically assisted procreation. We shall describe studies in human beings and in animals.展开更多
Human herpesviruses (HVs) have developed ingenious mechanisms that enable them to traverse the defenses of the central nervous system (CNS). The ability of HVs to enter a state of latency, a defining char- acteris...Human herpesviruses (HVs) have developed ingenious mechanisms that enable them to traverse the defenses of the central nervous system (CNS). The ability of HVs to enter a state of latency, a defining char- acteristic of this viral family, allows them to persist in the human host indefinitely. As such, HVs represent the most frequently detected pathogens in the brain. Under constant immune pressure, these infections are largely asymptomatic in healthy hosts. However, many neurotropic HVs have been directly connected with CNS pathology in the context of other stressors and genetic risk factors. In this review, we discuss the potential mechanisms by which neurotropic HVs contribute to neurodegenerative disease (NDD) patholo- gy by highlighting two prominent members of the HV family, herpes simplex virus 1 (HSV-1) and human herpesvirus 6 (HHV-6). We (i) introduce the infectious pathways and replicative cycles of HSV-1 and HHV-6 and then (ii) review the clinical evidence supporting associations between these viruses and the NDDs Alzheimer's disease (AD) and multiple sclerosis (MS), respectively. We then (iii) highlight and dis- cuss potential mechanisms by which these viruses exert negative effects on neurons and glia. Finally, we (iv) discuss how these viruses could interact with other disease-modifying factors to contribute to the initiation and/or progression of NDDs.展开更多
Human herpes virus 6 (HHV-6) infects > 95% of humans.Primary infection which occurs mostly during the f irst 2 years of life in the form of roseola infantum,non-spe cif ic febrile illness,or an asymptomatic illness...Human herpes virus 6 (HHV-6) infects > 95% of humans.Primary infection which occurs mostly during the f irst 2 years of life in the form of roseola infantum,non-spe cif ic febrile illness,or an asymptomatic illness,results in latency.Reactivation of latent HHV-6 is common after liver transplantation.Since the majority of human beings harbor the latent virus,HHV-6 infections after liver transplantation are most probably caused by end ogenous reactivation or superinfection.In a minority of cases,primary HHV-6 infection may occur when an HHV-6-seronegative individual receives a liver allograft from an HHV-6-seropositive donor.The vast major ity of HHV-6 infections after liver transplantation are asy-mptomatic.Only in a minority of cases,when HHV-6 causes a febrile illness associated with rash and mye- losuppression,hepatitis,gastroenteritis,pneumonitis,and encephalitis after liver transplantation.In addition,HHV-6 has been implicated in a variety of indirect effects,such as allograft rejection and increased predis- pos ition to and severity of other infections,includingcytomegalovirus,hepatitis C virus,and opportunistic fungi.Because of the uncommon nature of the clinical illnesses directly attributed to HHV-6,there is currently no recommended HHV-6-specific approach prevention after liver transplantation.Asymptomatic HHV-6 infection does not require antiviral treatment,while treatment of established HHV-6 disease is treated with intravenous ganciclovir,foscarnet,or cidofovir and this should be com plemented by a reduction in immunosuppression.展开更多
AIM To evaluate the impact of the Glu167Lys(E167K) transmembrane 6 superfamily member 2(TM6SF2) variant on the biochemical and morphologic expression of liver lesions in human immunodeficiency virus(HIV)/hepatitis C v...AIM To evaluate the impact of the Glu167Lys(E167K) transmembrane 6 superfamily member 2(TM6SF2) variant on the biochemical and morphologic expression of liver lesions in human immunodeficiency virus(HIV)/hepatitis C virus(HCV) co-infected patients.METHODS The study comprised 167 consecutive patients with HIV/HCV coinfection and biopsy-proven chronic hepatitis. A pathologist graded liver fibrosis and necroinflammation using the Ishak scoring system, and steatosis using Kleiner's scoring system. Patients were genotyped for TM6SF2 E167K(rs58542926) by real-time Polymerase chain reaction. The 167 patients, 35 therapy-naive and 132 receiving ART, were prevalently males(73.6%), the median age was 40.7 years and the immunological condition good(median CD4+ cells/mm3 = 505.5).RESULTS The 17 patients with the TM6SF2 E167 K variant, compared with the 150 with TM6SF2-E/E, showed higher AST(P = 0.02) and alanine aminotransferase(P = 0.02) and higher fibrosis score(3.1 ± 2.0 vs 2.3 ± 1.5, P = 0.05). In a multivariate analysis, TM6SF2 E167 K was independently associated with severe fibrosis. The same analysis showed that HCV-genotype 3, present in 42.2% of patients was an independent predictor of severe steatosis. The association of TM6SF2 E167 K with severe steatosis, absent for the whole group of 167 patients, was re-evaluated separately for HCVgenotype 3 and non-3 patients: No factor was independently associated with severe steatosis in the HCV-genotype-3 subgroup, whereas an independent association was observed between severe steatosis and TM6SF2 E167 K in non-3 HCV genotypes. No association between the TM6SF2 E167 K variant and severe liver necroinflammation was observed.CONCLUSION In HIV/HCV coinfection the TM6SF2 E167 K variant is an independent predictor of severe fibrosis, but appears to be independently associated with severe steatosis only for patients with a non-3 HCV genotype.展开更多
Human herpes viruses cause a range of human disorders including cold sores,roseola,genital warts and most importantly,tumours.These viruses cause chronic,latent and recurrent infections.Among them HHV-1,an alpha-herpe...Human herpes viruses cause a range of human disorders including cold sores,roseola,genital warts and most importantly,tumours.These viruses cause chronic,latent and recurrent infections.Among them HHV-1,an alpha-herpesvirus could become latent after a primary infection,becoming reactivated after later provocation. Epidemically,they are found everywhere and are neurotropic.They also have a rapid and highly regulated replication cycle and usually a broad host and cell range.This article summarizes and focuses on replication strategies of the virus.展开更多
Objective: To explore the functions and mechanisms of herpes simplex virus type I(HSV-1) while infecting human oral epithelial cells in vitro(being similar to the infection in vivo). Methods:An abundance of HSV-...Objective: To explore the functions and mechanisms of herpes simplex virus type I(HSV-1) while infecting human oral epithelial cells in vitro(being similar to the infection in vivo). Methods:An abundance of HSV-1 strains amplified in Vero cells were used to infect human oral epithelial cells. The culture supernatant was collected to infect Vero cells again. Morphology of HSV-1 was identified by inverted microscope and transmission electron microscope. Nucleic acid of the virus was detected by PCR. Results:The infected human oral epithelial cells didn' t display an obvious cytopathic effect(CPE) under inverted microscope(while Vero cells which were infected by the culture supernatant showed typical(CPE). The virus particles were not observed in the cytoplasm nor in nucleus of human oral epithelial cells, however under transmission electron microscope in the cytoplasm of Vero cells, the nucleic acid of HSV-1 could be detected in infected human oral epithelial cells, by PCR. Conclusion-HSV-1 can successfully infect human oral epithelial cells. This model may provide a useful approach for studying the pathogenesis of herpes virus-associated periodontal disease.展开更多
Antiserum against PreS2 peptide was raised with a synthetic polypeptide from the rabbits.The anti-preS2 antibody and polymerized human serum albumin were used as reagents in aradioimmunoassay to detect preS2 and polym...Antiserum against PreS2 peptide was raised with a synthetic polypeptide from the rabbits.The anti-preS2 antibody and polymerized human serum albumin were used as reagents in aradioimmunoassay to detect preS2 and polymerized human serum albumin bindingactivity respectively. Both were absent in patients with hepatitis A or HBsAg negative chronic liver di-seases. In biopsy - proven patients with chronic active hepatitis (CAH)B, prevalences of bothmarkers were significantly higher at exacerbation that at remission stage of the disease, and so werein CAH than in chronic asymptomatic HBV carrier (AsC) with normal histology. Besides, the pre-valences were significantly higher in HBeAg positive group than in anti-HBe positive group.However, the polymerized human serum albumin binding activity and the preS2 were undoubtedlynot the same, as the prevalence of the latter was only 56.7% of the former.展开更多
AIM: To study persistence and replication of hepatitis C virus (HCV) in patients' peripheral blood mononuclear cells (PBMC) cultured in vitro. METHODS: Epstein Barr virus (EBV) was used to transform the hepatitis ...AIM: To study persistence and replication of hepatitis C virus (HCV) in patients' peripheral blood mononuclear cells (PBMC) cultured in vitro. METHODS: Epstein Barr virus (EBV) was used to transform the hepatitis C virus from a HCV positive patient to permanent lymphoblastoid cell lines (LCL). Positive and negative HCV RNA strands of the cultured cells and growth media were detected by reverse transcriptase-polymerase chain reaction (RT-PCR) each month. Core and NS5 proteins of HCV were further tested using immunohistochemical SP method and in situ RT-PCR. RESULTS: HCV RNA positive strands were consistently detected the cultured cells for one year. The negative-strand RNA in LCL cells and the positive-strand RNA in supernatants were observed intermittently. Immunohistochemical results medicated expression of HCV NS3 and C proteins in LCL cytoplasm mostly. The positive signal of PCR product was dark blue and mainly localized to the LCL cytoplasm. The RT-PCR signal was eliminated by overnight RNase digestion but not DNase digestion. CONCLUSION: HCV may exist and remain functional in a cultured cell line for a long period.展开更多
Various SARS-CoV-2-related coronaviruses have been increasingly identified in pangolins,showing a potential threat to humans.Here we report the infectivity and pathogenicity of the SARS-CoV-2-related virus,PCoV-GX/P2V...Various SARS-CoV-2-related coronaviruses have been increasingly identified in pangolins,showing a potential threat to humans.Here we report the infectivity and pathogenicity of the SARS-CoV-2-related virus,PCoV-GX/P2V,which was isolated from a Malayan pangolin(Manis javanica).PCoV-GX/P2V could grow in human hepatoma,colorectal adenocarcinoma cells,and human primary nasal epithelial cells.It replicated more efficiently in cells expressing human angiotensin-converting enzyme 2(hACE2)as SARS-CoV-2 did.After intranasal inoculation to the hACE2-transgenic mice,PCoV-GX/P2V not only replicated in nasal turbinate and lungs,but also caused interstitial pneumonia,characterized by infiltration of mixed inflammatory cells and multifocal alveolar hemorrhage.Existing population immunity established by SARS-CoV-2 infection and vaccination may not protect people from PCoV-GX/P2V infection.These findings further verify the hACE2 utility of PCoV-GX/P2V by in vivo experiments using authentic viruses and highlight the importance for intensive surveillance to prevent possible cross-species transmission.展开更多
Periodontitis is the inflammation of the supporting structures around the dentition.Several microbial agents,mostly bacteria,have been identified as causative factors for periodontal disease.On the other hand,oral cav...Periodontitis is the inflammation of the supporting structures around the dentition.Several microbial agents,mostly bacteria,have been identified as causative factors for periodontal disease.On the other hand,oral cavity is a rich reservoir for viruses since it contains a wide variety of cell types that can be targeted by viruses.Traditionally,the focus of research about the oral flora has been on bacteria because the most widespread oral diseases,like periodontitis and dental caries,are outcomes of bacterial infection.However,recently and especially after the emergence of coronavirus disease 2019,there is a growing tendency toward including viruses also into the scope of oral microbiome investigations.The global high prevalence of periodontitis and viral infections may point out to a concomitant or synergistic effect between the two.Although the exact nature of the mechanism still is not clearly understood,this could be speculated through the manipulation of the immune system by viruses;hence facilitating the furthermore colonization of the oral tissues by bacteria.This review provides an extensive and detailed update on the role of the most common viruses including herpes family(herpes simplex,varicella-zoster,Epstein-Barr,cytomegalovirus),Human papillomaviruses,Human immunodeficiency virus and severe acute respiratory syndrome coronavirus 2 in the initiation,progression and prognosis of periodontitis.展开更多
AIM:To investigate human epidermal growth factor receptor 2(HER2)-phosphatidylinositol 3-kinase(PI3K)-vAkt murine thymoma viral oncogene homolog signaling pathway.METHODS:We analyzed 231 formalin-fixed,paraffinembedde...AIM:To investigate human epidermal growth factor receptor 2(HER2)-phosphatidylinositol 3-kinase(PI3K)-vAkt murine thymoma viral oncogene homolog signaling pathway.METHODS:We analyzed 231 formalin-fixed,paraffinembedded gastric cancer tissue specimens from Japanese patients who had undergone surgical treatment.The patients' age,sex,tumor location,depth of invasion,pathological type,lymph node metastasis,and pathological stage were determined by a review of the medical records.Expression of HER2 was analyzed by immunohistochemistry(IHC) using the HercepTest TM kit.Standard criteria for HER2 positivity(0,1+,2+,and 3+) were used.Tumors that scored 3+ were considered HER2-positive.Expression of phospho Akt(pAkt) was also analyzed by IHC.Tumors were considered pAkt-positive when the percentage of positive tumor cells was 10% or more.PI3K,catalytic,alpha polypeptide(PIK3CA) mutations in exons 1,9 and 20 were analyzed by pyrosequencing.Epstein-Barr virus(EBV) infection was analyzed by in situ hybridization targeting EBV-encoded small RNA(EBER) with an EBER-RNA probe.Microsatellite instability(MSI) was analyzed by polymerase chain reaction using the mononucleotide markers BAT25 and BAT26.RESULTS:HER2 expression levels of 0,1+,2+ and 3+ were found in 167(72%),32(14%),12(5%) and 20(8.7%) samples,respectively.HER2 overexpression(IHC 3+) significantly correlated with intestinal histological type(15/20 vs 98 /205,P = 0.05).PIK3CA mutations were present in 20 cases(8.7%) and significantly correlated with MSI(10/20 vs 9/211,P < 0.01).The mutation frequency was high(21%) in T4 cancers and very low(6%) in T2 cancers.Mutations in exons 1,9 and 20 were detected in 5(2%),9(4%) and 7(3%) cases,respectively.Two new types of PIK3CA mutation,R88Q and R108H,were found in exon1.All PIK3CA mutations were heterozygous missense singlebase substitutions,the most common being H1047R(6/20,30%) in exon20.Eighteen cancers(8%) were EBV-positive and this positivity significantly correlated with a diffuse histological type(13/18 vs 93/198,P = 0.04).There were 7 cases of lymphoepithelioma-like carcinomas(LELC) and 6 of those cases were EBV-positive(percent/EBV:6/18,33%;percent/all LELC:6/7,86%).pAkt expression was positive in 119(53%) cases but showed no correlation with clinicopathological characteristics.pAkt expression was significantly correlated with HER2 overexpression(16/20 vs 103/211,P < 0.01) but not with PIK3CA mutations(12/20 vs 107/211,P = 0.37) or EBV infection(8/18 vs 103/211,P = 0.69).The frequency of pAkt expression was higher in cancers with exon20 mutations(100%) than in those with exon1(40%) or exon9(56%) mutations.One case showed both HER2 overexpression and EBV infection and 3 cases showed both PIK3CA mutations and EBV infection.However,no cases showed both PIK3CA mutations and HER2 overexpression.One EBVpositive cancer with PIK3CA mutation(H1047R) was MSI-positive.Three of these 4 cases were positive for pAkt expression.In survival analysis,pAkt expression significantly correlated with a poor prognosis(hazard ratio 1.75;95%CI:1.12-2.80,P = 0.02).CONCLUSION:HER2 expression,PIK3CA mutations and EBV infection in gastric cancer were characterized.pAkt expression significantly correlates with HER2 expression and with a poor prognosis.展开更多
Allicin, an antioxidant, is known for providing garlic with its unique fragrance and taste, as well as for its antimicrobial properties. Black garlic, a fermented form of garlic, contains higher levels of antioxidants...Allicin, an antioxidant, is known for providing garlic with its unique fragrance and taste, as well as for its antimicrobial properties. Black garlic, a fermented form of garlic, contains higher levels of antioxidants than fresh garlic. Antioxidants play a vital role in alleviating cellular stress during viral infections. Viral infections result in oxidative stress through the production of reactive oxidative species (ROS). A prolonged state of oxidative stress can result in cell death, DNA damage, and disease progression. In this study, black garlic extract (BGE) is evaluated for its ability to mitigate cytopathic effects and oxidative stress caused by herpes simplex virus-2 (HSV-2) infections in vitro. Antiviral assays were performed to determine the percent of viral inhibition resulting from treatment with the BGE. ROS-Glo<sup>TM</sup> H<sub>2</sub>O<sub>2</sub> assays were then completed to measure the post-infection ROS levels of BGE-treated virus and cells. The results thus far suggest that BGE may inhibit viral infection and decrease levels of oxidative stress.展开更多
Objective:To investigate the incidence of human cytomegalo virus(HCMV) in pregnant women.Methods: One hundred and twenty two(122) blood samples and 80 umbilical cord fluids were tested for IgG and IgM respectively usi...Objective:To investigate the incidence of human cytomegalo virus(HCMV) in pregnant women.Methods: One hundred and twenty two(122) blood samples and 80 umbilical cord fluids were tested for IgG and IgM respectively using the enzyme linked immunosorbent assay(ELISA).Results:Of the 122 samples screened for IgG and IgM only 56(47.1%) tested positive for IgG while 63(52.9%) were positive for IgM with 3 samples non-specific.Pregnant women with signs of normal pregnancy made up 60%of the positive results while 20%had a history of ectopic pregnancy and 20%with a history of miscarriages.Of the total of 80 umbilical cord fluids tested,only 59(73.8) tested positive.Eleven of the selected 40 umblical cord fluid was positive to IgG to human cytomegalovirus along with mother and child.Antibody titration result gave diagnostic titre for both IgG and IgM from the 40 umbilical cord fluids.There was a significant relationship between mother,child and umbilical cord fluids(χ~2 = 1.360,CI = 99%,P = 0.568).Conclusion:There could be a possible neonatal infection,and the infection is common among toddlers and children of pre-school age.展开更多
BACKGROUND Kaposi’s sarcoma(KS)is a malignancy that usually affects the skin of the lower extremities,and may involve internal organs.It originates from the vascular endothelium.It is well known that the development ...BACKGROUND Kaposi’s sarcoma(KS)is a malignancy that usually affects the skin of the lower extremities,and may involve internal organs.It originates from the vascular endothelium.It is well known that the development of KS is associated with human herpes virus 8(i.e.HHV8)infections.Sporadic KS cases have mainly been found in Africa.Isolated splenic KS in Asia has rarely been reported.We present here a case of KS primarily involving the spleen in a human immunodeficiency virus(HIV)-negative Chinese patient.CASE SUMMARY A 50-year-old male patient was admitted to hospital due to abdominal distension and discomfort,reduced food intake and weight loss.Medical examination revealed that the patient had moderate anemia,a low platelet count,slight fatty liver and a huge mass in the spleen.Spleen lymphoma was considered.An anti-HIV test was negative.The whole spleen was surgically excised.The final pathological diagnosis was nodular stage spleen KS,and the patient underwent total splenectomy.He recovered well and was discharged from hospital 12 d after surgery.Two weeks later,the patient developed liver metastasis and died within 1 mo after surgery.CONCLUSION KS is difficult to diagnose and pathological examination is necessary.KS has a poor prognosis and should be diagnosed and treated early to improve survival.展开更多
Objective Both the 2, 6 linkage and its topology on target cells are critical for the recognition by human influenza virus. The binding preference of avian flu virus H5N1 HA to the 2, 3-1inked sialylated glycans is co...Objective Both the 2, 6 linkage and its topology on target cells are critical for the recognition by human influenza virus. The binding preference of avian flu virus H5N1 HA to the 2, 3-1inked sialylated glycans is considered the major factor limiting its efficient infection and transmission in humans. To monitor potential adaptation of H5N1 virus in human population, the surveillance of receptor-binding specificity was undertaken in China. Methods The binding specificity of 32 human H5N1 virus strains isolated from 2003 to 2009 was tested by 2, 3-specific sialidase-treated chicken red blood cell (CRBC) agglutination assay and a solid-phase direct binding assay with synthetic sialylglycopolymers. Results Dual binding preference to 2, 3 and 2, 6-glycans were found in two strains: A/Guangdong/1/06 (A/GD/1/06) and A/Guangxi/1/08 (A/GX/1/08). Though minor effect of short-2, 6-binding was detected in A/GX/1/08 at a low virus titer, both showed high affinity to the oligosaccharide at a high load. Notably both are of the long-2, 6-recognition, with the same topology as that of human H1N1 and H3N2 viruses. Conclusion The findings suggest that human H5N1 virus in China likely acquired the potential human-adaptation ability. Further research and surveillance on receptor-binding specificity of H5N1 viruses are required.展开更多
The specimens of 111 cervical carcinomas. 68 chronic cervicitis and 43 normal cervical exfoliated epithelial cells were examined for the presence of HSV2 DNA sequences with DNA hybridization using HSV2 BgL Ⅱ N fragm...The specimens of 111 cervical carcinomas. 68 chronic cervicitis and 43 normal cervical exfoliated epithelial cells were examined for the presence of HSV2 DNA sequences with DNA hybridization using HSV2 BgL Ⅱ N fragment probe labelled by 32PdCTP. The result showed that the infection rates of HSV2 in the samples of cervical cancer.chronic cervicitis and normal epithelial cells were 1 4. 41 %(16/111). 27.94%( 19/68) and 25.58% ( 11/43),respectively. It was implied that early stages carcinogenesis of cervical epithelial cells might be correlated with the HSV2 infection.Sixteen HSV 2 positive samples of cervical carcinomas were also examined for the presence of the sequences homologous to human papillomavirus (HPV) type 6B/11. 16 and 18 DNA using dot blot hybridization (Tm17℃). The result indicated that 13 out of 16 were HPV 16 DNA hybridization positive accounting for 81. 2% of all HSV-2 positive samples and none of them were positive for HPV type 6B/11 and 18. The result indicated that double infection of HSV 2 and HPV16 in the same cervical carcinoma tissues may provide a strong evidence of the viral synergistic interaction in the induction of female cervical展开更多
In this study, we investigated the in vitro antiviral activity of the mycelia of higher mushrooms against influenza virus type A(serotype H1N1) and herpes simplex virus type 2(HSV-2), strain BH. All 10 investigated mu...In this study, we investigated the in vitro antiviral activity of the mycelia of higher mushrooms against influenza virus type A(serotype H1N1) and herpes simplex virus type 2(HSV-2), strain BH. All 10 investigated mushroom species inhibited the reproduction of influenza virus strain A/FM/1/47(H1N1) in MDCK cells reducing the infectious titer by 2.0–6.0 lg ID50. Four species, Pleurotus ostreatus, Fomes fomentarius, Auriporia aurea, and Trametes versicolor, were also determined to be effective against HSV-2 strain BH in RK-13 cells, with similar levels of inhibition as for influenza. For some of the investigated mushroom species—Pleurotus eryngii, Lyophyllum shimeji, and Flammulina velutipes—this is the first report of an anti-influenza effect. This study also reports the first data on the medicinal properties of A. aurea, including anti-influenza and antiherpetic activities. T. versicolor 353 mycelium was found to have a high therapeutic index(324.67), and may be a promising material for the pharmaceutical industry as an anti-influenza and antiherpetic agent with low toxicity. Mycelia with antiviral activity were obtained in our investigation by bioconversion of agricultural wastes(amaranth flour after CO2 extraction), which would reduce the cost of the final product and solve some ecological problems.展开更多
文摘BACKGROUND The co-occurrence of Anti-phospholipase A2 receptor-associated membranous nephropathy(anti-PLA2R-MN)and human immunodeficiency virus(HIV)infection is a rare clinical scenario,presenting significant challenges in terms of management and treatment.CASE SUMMARY A 32-year-old Chinese male diagnosed with HIV infection presented with a clinical history of proteinuria persisting for over two years.A kidney biopsy demonstrated subepithelial immune complex deposition and a thickened glomerular basement membrane,indicative of stage I-II membranous nephro-pathy.Immunofluorescence staining revealed granular deposition of PLA2R(3+)along the glomerular capillary loops,corroborated by a strongly positive anti-PLA2R antibody test(1:320).Initial treatment involving losartan potassium,rivaroxaban,tacrolimus,and rituximab was discontinued due to either poor effec-tiveness or the occurrence of adverse events.Following a regimen of weekly subcutaneous injections of telitacicept(160 mg),a marked decline in the 24 h urine protein was observed within a three-month period,accompanied by a rise in serum albumin level.No significant reductions in peripheral blood CD3+CD4+T and CD3+CD8+T cell counts were detected.The patient's physical and psychological conditions showed significant improvements,with no adverse events reported during the treatment course.CONCLUSION Telitacicept might offer a potential therapeutic avenue for patients diagnosed with anti-PLA2R-MN concomitant with HIV infection.
文摘The possibility of infection of the human male genital tract by human herpes virus type 2 (HSV2) or human cytomegalovirus (HCMV) is well established and their sexual transmission has been the object of many studies. Moreover, medically assisted procreation, which helps in numerous fertility problems, raises the question of new viral risks linked to the application of these new technologies. In this review, we shall consider current knowledge in terms of the presence of HSV 2 and HCMV in the different parts of the genital tract of immunocompetent or immunodepressed men. We shall also consider the possibility of viral transmission by the sexual act or by the various techniques used in medically assisted procreation. We shall describe studies in human beings and in animals.
文摘Human herpesviruses (HVs) have developed ingenious mechanisms that enable them to traverse the defenses of the central nervous system (CNS). The ability of HVs to enter a state of latency, a defining char- acteristic of this viral family, allows them to persist in the human host indefinitely. As such, HVs represent the most frequently detected pathogens in the brain. Under constant immune pressure, these infections are largely asymptomatic in healthy hosts. However, many neurotropic HVs have been directly connected with CNS pathology in the context of other stressors and genetic risk factors. In this review, we discuss the potential mechanisms by which neurotropic HVs contribute to neurodegenerative disease (NDD) patholo- gy by highlighting two prominent members of the HV family, herpes simplex virus 1 (HSV-1) and human herpesvirus 6 (HHV-6). We (i) introduce the infectious pathways and replicative cycles of HSV-1 and HHV-6 and then (ii) review the clinical evidence supporting associations between these viruses and the NDDs Alzheimer's disease (AD) and multiple sclerosis (MS), respectively. We then (iii) highlight and dis- cuss potential mechanisms by which these viruses exert negative effects on neurons and glia. Finally, we (iv) discuss how these viruses could interact with other disease-modifying factors to contribute to the initiation and/or progression of NDDs.
文摘Human herpes virus 6 (HHV-6) infects > 95% of humans.Primary infection which occurs mostly during the f irst 2 years of life in the form of roseola infantum,non-spe cif ic febrile illness,or an asymptomatic illness,results in latency.Reactivation of latent HHV-6 is common after liver transplantation.Since the majority of human beings harbor the latent virus,HHV-6 infections after liver transplantation are most probably caused by end ogenous reactivation or superinfection.In a minority of cases,primary HHV-6 infection may occur when an HHV-6-seronegative individual receives a liver allograft from an HHV-6-seropositive donor.The vast major ity of HHV-6 infections after liver transplantation are asy-mptomatic.Only in a minority of cases,when HHV-6 causes a febrile illness associated with rash and mye- losuppression,hepatitis,gastroenteritis,pneumonitis,and encephalitis after liver transplantation.In addition,HHV-6 has been implicated in a variety of indirect effects,such as allograft rejection and increased predis- pos ition to and severity of other infections,includingcytomegalovirus,hepatitis C virus,and opportunistic fungi.Because of the uncommon nature of the clinical illnesses directly attributed to HHV-6,there is currently no recommended HHV-6-specific approach prevention after liver transplantation.Asymptomatic HHV-6 infection does not require antiviral treatment,while treatment of established HHV-6 disease is treated with intravenous ganciclovir,foscarnet,or cidofovir and this should be com plemented by a reduction in immunosuppression.
文摘AIM To evaluate the impact of the Glu167Lys(E167K) transmembrane 6 superfamily member 2(TM6SF2) variant on the biochemical and morphologic expression of liver lesions in human immunodeficiency virus(HIV)/hepatitis C virus(HCV) co-infected patients.METHODS The study comprised 167 consecutive patients with HIV/HCV coinfection and biopsy-proven chronic hepatitis. A pathologist graded liver fibrosis and necroinflammation using the Ishak scoring system, and steatosis using Kleiner's scoring system. Patients were genotyped for TM6SF2 E167K(rs58542926) by real-time Polymerase chain reaction. The 167 patients, 35 therapy-naive and 132 receiving ART, were prevalently males(73.6%), the median age was 40.7 years and the immunological condition good(median CD4+ cells/mm3 = 505.5).RESULTS The 17 patients with the TM6SF2 E167 K variant, compared with the 150 with TM6SF2-E/E, showed higher AST(P = 0.02) and alanine aminotransferase(P = 0.02) and higher fibrosis score(3.1 ± 2.0 vs 2.3 ± 1.5, P = 0.05). In a multivariate analysis, TM6SF2 E167 K was independently associated with severe fibrosis. The same analysis showed that HCV-genotype 3, present in 42.2% of patients was an independent predictor of severe steatosis. The association of TM6SF2 E167 K with severe steatosis, absent for the whole group of 167 patients, was re-evaluated separately for HCVgenotype 3 and non-3 patients: No factor was independently associated with severe steatosis in the HCV-genotype-3 subgroup, whereas an independent association was observed between severe steatosis and TM6SF2 E167 K in non-3 HCV genotypes. No association between the TM6SF2 E167 K variant and severe liver necroinflammation was observed.CONCLUSION In HIV/HCV coinfection the TM6SF2 E167 K variant is an independent predictor of severe fibrosis, but appears to be independently associated with severe steatosis only for patients with a non-3 HCV genotype.
文摘Human herpes viruses cause a range of human disorders including cold sores,roseola,genital warts and most importantly,tumours.These viruses cause chronic,latent and recurrent infections.Among them HHV-1,an alpha-herpesvirus could become latent after a primary infection,becoming reactivated after later provocation. Epidemically,they are found everywhere and are neurotropic.They also have a rapid and highly regulated replication cycle and usually a broad host and cell range.This article summarizes and focuses on replication strategies of the virus.
文摘Objective: To explore the functions and mechanisms of herpes simplex virus type I(HSV-1) while infecting human oral epithelial cells in vitro(being similar to the infection in vivo). Methods:An abundance of HSV-1 strains amplified in Vero cells were used to infect human oral epithelial cells. The culture supernatant was collected to infect Vero cells again. Morphology of HSV-1 was identified by inverted microscope and transmission electron microscope. Nucleic acid of the virus was detected by PCR. Results:The infected human oral epithelial cells didn' t display an obvious cytopathic effect(CPE) under inverted microscope(while Vero cells which were infected by the culture supernatant showed typical(CPE). The virus particles were not observed in the cytoplasm nor in nucleus of human oral epithelial cells, however under transmission electron microscope in the cytoplasm of Vero cells, the nucleic acid of HSV-1 could be detected in infected human oral epithelial cells, by PCR. Conclusion-HSV-1 can successfully infect human oral epithelial cells. This model may provide a useful approach for studying the pathogenesis of herpes virus-associated periodontal disease.
文摘Antiserum against PreS2 peptide was raised with a synthetic polypeptide from the rabbits.The anti-preS2 antibody and polymerized human serum albumin were used as reagents in aradioimmunoassay to detect preS2 and polymerized human serum albumin bindingactivity respectively. Both were absent in patients with hepatitis A or HBsAg negative chronic liver di-seases. In biopsy - proven patients with chronic active hepatitis (CAH)B, prevalences of bothmarkers were significantly higher at exacerbation that at remission stage of the disease, and so werein CAH than in chronic asymptomatic HBV carrier (AsC) with normal histology. Besides, the pre-valences were significantly higher in HBeAg positive group than in anti-HBe positive group.However, the polymerized human serum albumin binding activity and the preS2 were undoubtedlynot the same, as the prevalence of the latter was only 56.7% of the former.
基金The paper was support by a grant from the Ministry Youth Research of China,No.98-1-269
文摘AIM: To study persistence and replication of hepatitis C virus (HCV) in patients' peripheral blood mononuclear cells (PBMC) cultured in vitro. METHODS: Epstein Barr virus (EBV) was used to transform the hepatitis C virus from a HCV positive patient to permanent lymphoblastoid cell lines (LCL). Positive and negative HCV RNA strands of the cultured cells and growth media were detected by reverse transcriptase-polymerase chain reaction (RT-PCR) each month. Core and NS5 proteins of HCV were further tested using immunohistochemical SP method and in situ RT-PCR. RESULTS: HCV RNA positive strands were consistently detected the cultured cells for one year. The negative-strand RNA in LCL cells and the positive-strand RNA in supernatants were observed intermittently. Immunohistochemical results medicated expression of HCV NS3 and C proteins in LCL cytoplasm mostly. The positive signal of PCR product was dark blue and mainly localized to the LCL cytoplasm. The RT-PCR signal was eliminated by overnight RNase digestion but not DNase digestion. CONCLUSION: HCV may exist and remain functional in a cultured cell line for a long period.
基金supported by the National Natural Science Foundation of China(81621005)。
文摘Various SARS-CoV-2-related coronaviruses have been increasingly identified in pangolins,showing a potential threat to humans.Here we report the infectivity and pathogenicity of the SARS-CoV-2-related virus,PCoV-GX/P2V,which was isolated from a Malayan pangolin(Manis javanica).PCoV-GX/P2V could grow in human hepatoma,colorectal adenocarcinoma cells,and human primary nasal epithelial cells.It replicated more efficiently in cells expressing human angiotensin-converting enzyme 2(hACE2)as SARS-CoV-2 did.After intranasal inoculation to the hACE2-transgenic mice,PCoV-GX/P2V not only replicated in nasal turbinate and lungs,but also caused interstitial pneumonia,characterized by infiltration of mixed inflammatory cells and multifocal alveolar hemorrhage.Existing population immunity established by SARS-CoV-2 infection and vaccination may not protect people from PCoV-GX/P2V infection.These findings further verify the hACE2 utility of PCoV-GX/P2V by in vivo experiments using authentic viruses and highlight the importance for intensive surveillance to prevent possible cross-species transmission.
文摘Periodontitis is the inflammation of the supporting structures around the dentition.Several microbial agents,mostly bacteria,have been identified as causative factors for periodontal disease.On the other hand,oral cavity is a rich reservoir for viruses since it contains a wide variety of cell types that can be targeted by viruses.Traditionally,the focus of research about the oral flora has been on bacteria because the most widespread oral diseases,like periodontitis and dental caries,are outcomes of bacterial infection.However,recently and especially after the emergence of coronavirus disease 2019,there is a growing tendency toward including viruses also into the scope of oral microbiome investigations.The global high prevalence of periodontitis and viral infections may point out to a concomitant or synergistic effect between the two.Although the exact nature of the mechanism still is not clearly understood,this could be speculated through the manipulation of the immune system by viruses;hence facilitating the furthermore colonization of the oral tissues by bacteria.This review provides an extensive and detailed update on the role of the most common viruses including herpes family(herpes simplex,varicella-zoster,Epstein-Barr,cytomegalovirus),Human papillomaviruses,Human immunodeficiency virus and severe acute respiratory syndrome coronavirus 2 in the initiation,progression and prognosis of periodontitis.
基金Supported by Grants-in-Aid for Scientific Research from the Ministry of Education,Culture,Sports,Science and Technology of Japan,to Yamamoto H and Shinomura Y
文摘AIM:To investigate human epidermal growth factor receptor 2(HER2)-phosphatidylinositol 3-kinase(PI3K)-vAkt murine thymoma viral oncogene homolog signaling pathway.METHODS:We analyzed 231 formalin-fixed,paraffinembedded gastric cancer tissue specimens from Japanese patients who had undergone surgical treatment.The patients' age,sex,tumor location,depth of invasion,pathological type,lymph node metastasis,and pathological stage were determined by a review of the medical records.Expression of HER2 was analyzed by immunohistochemistry(IHC) using the HercepTest TM kit.Standard criteria for HER2 positivity(0,1+,2+,and 3+) were used.Tumors that scored 3+ were considered HER2-positive.Expression of phospho Akt(pAkt) was also analyzed by IHC.Tumors were considered pAkt-positive when the percentage of positive tumor cells was 10% or more.PI3K,catalytic,alpha polypeptide(PIK3CA) mutations in exons 1,9 and 20 were analyzed by pyrosequencing.Epstein-Barr virus(EBV) infection was analyzed by in situ hybridization targeting EBV-encoded small RNA(EBER) with an EBER-RNA probe.Microsatellite instability(MSI) was analyzed by polymerase chain reaction using the mononucleotide markers BAT25 and BAT26.RESULTS:HER2 expression levels of 0,1+,2+ and 3+ were found in 167(72%),32(14%),12(5%) and 20(8.7%) samples,respectively.HER2 overexpression(IHC 3+) significantly correlated with intestinal histological type(15/20 vs 98 /205,P = 0.05).PIK3CA mutations were present in 20 cases(8.7%) and significantly correlated with MSI(10/20 vs 9/211,P < 0.01).The mutation frequency was high(21%) in T4 cancers and very low(6%) in T2 cancers.Mutations in exons 1,9 and 20 were detected in 5(2%),9(4%) and 7(3%) cases,respectively.Two new types of PIK3CA mutation,R88Q and R108H,were found in exon1.All PIK3CA mutations were heterozygous missense singlebase substitutions,the most common being H1047R(6/20,30%) in exon20.Eighteen cancers(8%) were EBV-positive and this positivity significantly correlated with a diffuse histological type(13/18 vs 93/198,P = 0.04).There were 7 cases of lymphoepithelioma-like carcinomas(LELC) and 6 of those cases were EBV-positive(percent/EBV:6/18,33%;percent/all LELC:6/7,86%).pAkt expression was positive in 119(53%) cases but showed no correlation with clinicopathological characteristics.pAkt expression was significantly correlated with HER2 overexpression(16/20 vs 103/211,P < 0.01) but not with PIK3CA mutations(12/20 vs 107/211,P = 0.37) or EBV infection(8/18 vs 103/211,P = 0.69).The frequency of pAkt expression was higher in cancers with exon20 mutations(100%) than in those with exon1(40%) or exon9(56%) mutations.One case showed both HER2 overexpression and EBV infection and 3 cases showed both PIK3CA mutations and EBV infection.However,no cases showed both PIK3CA mutations and HER2 overexpression.One EBVpositive cancer with PIK3CA mutation(H1047R) was MSI-positive.Three of these 4 cases were positive for pAkt expression.In survival analysis,pAkt expression significantly correlated with a poor prognosis(hazard ratio 1.75;95%CI:1.12-2.80,P = 0.02).CONCLUSION:HER2 expression,PIK3CA mutations and EBV infection in gastric cancer were characterized.pAkt expression significantly correlates with HER2 expression and with a poor prognosis.
文摘Allicin, an antioxidant, is known for providing garlic with its unique fragrance and taste, as well as for its antimicrobial properties. Black garlic, a fermented form of garlic, contains higher levels of antioxidants than fresh garlic. Antioxidants play a vital role in alleviating cellular stress during viral infections. Viral infections result in oxidative stress through the production of reactive oxidative species (ROS). A prolonged state of oxidative stress can result in cell death, DNA damage, and disease progression. In this study, black garlic extract (BGE) is evaluated for its ability to mitigate cytopathic effects and oxidative stress caused by herpes simplex virus-2 (HSV-2) infections in vitro. Antiviral assays were performed to determine the percent of viral inhibition resulting from treatment with the BGE. ROS-Glo<sup>TM</sup> H<sub>2</sub>O<sub>2</sub> assays were then completed to measure the post-infection ROS levels of BGE-treated virus and cells. The results thus far suggest that BGE may inhibit viral infection and decrease levels of oxidative stress.
文摘Objective:To investigate the incidence of human cytomegalo virus(HCMV) in pregnant women.Methods: One hundred and twenty two(122) blood samples and 80 umbilical cord fluids were tested for IgG and IgM respectively using the enzyme linked immunosorbent assay(ELISA).Results:Of the 122 samples screened for IgG and IgM only 56(47.1%) tested positive for IgG while 63(52.9%) were positive for IgM with 3 samples non-specific.Pregnant women with signs of normal pregnancy made up 60%of the positive results while 20%had a history of ectopic pregnancy and 20%with a history of miscarriages.Of the total of 80 umbilical cord fluids tested,only 59(73.8) tested positive.Eleven of the selected 40 umblical cord fluid was positive to IgG to human cytomegalovirus along with mother and child.Antibody titration result gave diagnostic titre for both IgG and IgM from the 40 umbilical cord fluids.There was a significant relationship between mother,child and umbilical cord fluids(χ~2 = 1.360,CI = 99%,P = 0.568).Conclusion:There could be a possible neonatal infection,and the infection is common among toddlers and children of pre-school age.
文摘BACKGROUND Kaposi’s sarcoma(KS)is a malignancy that usually affects the skin of the lower extremities,and may involve internal organs.It originates from the vascular endothelium.It is well known that the development of KS is associated with human herpes virus 8(i.e.HHV8)infections.Sporadic KS cases have mainly been found in Africa.Isolated splenic KS in Asia has rarely been reported.We present here a case of KS primarily involving the spleen in a human immunodeficiency virus(HIV)-negative Chinese patient.CASE SUMMARY A 50-year-old male patient was admitted to hospital due to abdominal distension and discomfort,reduced food intake and weight loss.Medical examination revealed that the patient had moderate anemia,a low platelet count,slight fatty liver and a huge mass in the spleen.Spleen lymphoma was considered.An anti-HIV test was negative.The whole spleen was surgically excised.The final pathological diagnosis was nodular stage spleen KS,and the patient underwent total splenectomy.He recovered well and was discharged from hospital 12 d after surgery.Two weeks later,the patient developed liver metastasis and died within 1 mo after surgery.CONCLUSION KS is difficult to diagnose and pathological examination is necessary.KS has a poor prognosis and should be diagnosed and treated early to improve survival.
基金supported by the Ministry of Science and Technology (project No.2007AA02Z417)
文摘Objective Both the 2, 6 linkage and its topology on target cells are critical for the recognition by human influenza virus. The binding preference of avian flu virus H5N1 HA to the 2, 3-1inked sialylated glycans is considered the major factor limiting its efficient infection and transmission in humans. To monitor potential adaptation of H5N1 virus in human population, the surveillance of receptor-binding specificity was undertaken in China. Methods The binding specificity of 32 human H5N1 virus strains isolated from 2003 to 2009 was tested by 2, 3-specific sialidase-treated chicken red blood cell (CRBC) agglutination assay and a solid-phase direct binding assay with synthetic sialylglycopolymers. Results Dual binding preference to 2, 3 and 2, 6-glycans were found in two strains: A/Guangdong/1/06 (A/GD/1/06) and A/Guangxi/1/08 (A/GX/1/08). Though minor effect of short-2, 6-binding was detected in A/GX/1/08 at a low virus titer, both showed high affinity to the oligosaccharide at a high load. Notably both are of the long-2, 6-recognition, with the same topology as that of human H1N1 and H3N2 viruses. Conclusion The findings suggest that human H5N1 virus in China likely acquired the potential human-adaptation ability. Further research and surveillance on receptor-binding specificity of H5N1 viruses are required.
文摘The specimens of 111 cervical carcinomas. 68 chronic cervicitis and 43 normal cervical exfoliated epithelial cells were examined for the presence of HSV2 DNA sequences with DNA hybridization using HSV2 BgL Ⅱ N fragment probe labelled by 32PdCTP. The result showed that the infection rates of HSV2 in the samples of cervical cancer.chronic cervicitis and normal epithelial cells were 1 4. 41 %(16/111). 27.94%( 19/68) and 25.58% ( 11/43),respectively. It was implied that early stages carcinogenesis of cervical epithelial cells might be correlated with the HSV2 infection.Sixteen HSV 2 positive samples of cervical carcinomas were also examined for the presence of the sequences homologous to human papillomavirus (HPV) type 6B/11. 16 and 18 DNA using dot blot hybridization (Tm17℃). The result indicated that 13 out of 16 were HPV 16 DNA hybridization positive accounting for 81. 2% of all HSV-2 positive samples and none of them were positive for HPV type 6B/11 and 18. The result indicated that double infection of HSV 2 and HPV16 in the same cervical carcinoma tissues may provide a strong evidence of the viral synergistic interaction in the induction of female cervical
文摘In this study, we investigated the in vitro antiviral activity of the mycelia of higher mushrooms against influenza virus type A(serotype H1N1) and herpes simplex virus type 2(HSV-2), strain BH. All 10 investigated mushroom species inhibited the reproduction of influenza virus strain A/FM/1/47(H1N1) in MDCK cells reducing the infectious titer by 2.0–6.0 lg ID50. Four species, Pleurotus ostreatus, Fomes fomentarius, Auriporia aurea, and Trametes versicolor, were also determined to be effective against HSV-2 strain BH in RK-13 cells, with similar levels of inhibition as for influenza. For some of the investigated mushroom species—Pleurotus eryngii, Lyophyllum shimeji, and Flammulina velutipes—this is the first report of an anti-influenza effect. This study also reports the first data on the medicinal properties of A. aurea, including anti-influenza and antiherpetic activities. T. versicolor 353 mycelium was found to have a high therapeutic index(324.67), and may be a promising material for the pharmaceutical industry as an anti-influenza and antiherpetic agent with low toxicity. Mycelia with antiviral activity were obtained in our investigation by bioconversion of agricultural wastes(amaranth flour after CO2 extraction), which would reduce the cost of the final product and solve some ecological problems.