BACKGROUND Acute acalculous cholecystitis(AAC)is inflammation of the gallbladder without evidence of calculi.Although rarely reported,its etiologies include hepatitis virus infection(e.g.,hepatitis A virus,HAV)and adu...BACKGROUND Acute acalculous cholecystitis(AAC)is inflammation of the gallbladder without evidence of calculi.Although rarely reported,its etiologies include hepatitis virus infection(e.g.,hepatitis A virus,HAV)and adult-onset Still’s disease(AOSD).There are no reports of HAV-associated AAC in an AOSD patient.CASE SUMMARY Here we report a rare case of HAV infection-associated AAC in a 39-year-old woman who had a history of AOSD.The patient presented with an acute abdomen and hypotension.Elevated hepatobiliary enzymes and a thickened and distended gallbladder without gallstones on ultrasonography suggested AAC,but there were no signs of anemia nor thrombocytopenia.Serological screening revealed anti-HAV IgM antibodies.Steroid treatment did not alleviate her symptoms,and she was referred for laparoscopic cholecystectomy.The resected gallbladder was hydropic without perforation,and her clinical signs gradually improved after surgery.CONCLUSION AAC can be caused by HAV in AOSD patients.It is crucial to search for the underlying etiology for AAC,especially uncommon viral causes.展开更多
BACKGROUND Emerging studies indicate the critical involvement of microorganisms,such as Epstein-Barr virus(EBV),in the pathogenesis of inflammatory bowel disease(IBD).Immunosuppressive therapies for IBD can reactivate...BACKGROUND Emerging studies indicate the critical involvement of microorganisms,such as Epstein-Barr virus(EBV),in the pathogenesis of inflammatory bowel disease(IBD).Immunosuppressive therapies for IBD can reactivate latent EBV,complicating the clinical course of IBD.Moreover,the clinical significance of EBV expression in B lymphocytes derived from IBD patients’intestinal tissues has not been explored in detail.AIM To explore the clinical significance of latent EBV infection in IBD patients.METHODS Latent EBV infection was determined by double staining for EBV encoded RNA and CD20 in colon specimens of 43 IBD patients who underwent bowel resection.Based on the staining results,the patients were divided into two groups,according to their latent EBV infection states-negative(n=33)and positive(n=10).Illness severity of IBD were assigned according to Crohn’s disease activity index(ulcerative colitis)and Mayo staging system(Crohn’s disease).The clinicpathological data were analyzed between the two different latent EBV groups and also between the mild-to-moderate and severe disease groups.RESULTS Systolic pressure(P=0.005),variety of disease(P=0.005),the severity of illness(P=0.002),and pre-op corticosteroids(P=0.025)were significantly different between the EBV-negative and EBV-positive groups.Systolic pressure(P=0.001),variety of disease(P=0.000),pre-op corticosteroids(P=0.011)and EBV infection(P=0.003)were significantly different between the mild-to-moderate and severe disease groups.CONCLUSION IBD patients with latent EBV infection may manifest more severe illnesses.It is suggested that the role of EBV in IBD development should be further investigated,latent EBV infection in patients with serious IBD should be closely monitored,and therapeutic course should be optimized.展开更多
BACKGROUND Inflammatory bowel disease(IBD)is an autoimmune condition treated with immunosuppressive drugs.However,the need for immune system suppression becomes questionable when infection with the human immunodeficie...BACKGROUND Inflammatory bowel disease(IBD)is an autoimmune condition treated with immunosuppressive drugs.However,the need for immune system suppression becomes questionable when infection with the human immunodeficiency virus(HIV)occurs simultaneously and impacts the course of IBD.Our reported case represents the clinical course,prescribed treatment and its effect,as well as clinical challenges faced by physicians in a combination of such diseases.We also present a comprehensive literature review of similar cases.CASE SUMMARY A 49-year-old woman suffering from a newly diagnosed Crohn’s disease was hospitalized due to exacerbated symptoms(abdominal pain,fever,and weight loss).During her hospital stay,she tested positive for HIV.With conservative treatment,the patient improved and was discharged.In the outpatient clinic,her HIV infection was confirmed as stage C3,and antiretroviral treatment was initiated immediately.That notwithstanding,soon the patient was rehospitalized with pulmonary embolism and developed a series of complications because of the subsequent coexistence of IBD and HIV.After intensive and meticulous treatment,the patient’s condition has improved and she remains in remission.CONCLUSION The paucity of studies and data on the coexistence of HIV and IBD leaves clinicians doubting the optimal treatment options.展开更多
To further understand the generation and development of coinfection of Marek's disease virus (MDV) and reticuloendotheliosis virus (REV) in broiler breeders, and then find the method and optimal time of different...To further understand the generation and development of coinfection of Marek's disease virus (MDV) and reticuloendotheliosis virus (REV) in broiler breeders, and then find the method and optimal time of differential diagnosis for complex clinic multiple infection, the authors studied the pathohistological changes, apoptosis, immunohistochemistry (immunofluorescence), and ultrastructure of tumor tissues of broiler breeders inoculated with MDV and REV. The study showed that proliferation of small lymphocytes was seen in the main organs at the age of 1 week, then immature lymphocytes, all kinds of lymphocytes, primitive reticulum cells, and Marek's disease cells (MDCs) were observed at 2-9 weeks. Apoptosis of lymphocytes could not be seen until the age of 10 weeks in the immune system. Immunohistochemistry detection showed that the positive signs of MDV and REV antigen were observed in the main organs at 2 weeks of age. Multi-morphology lymphocytes, MDV, and REV, mitotic figures and apoptosis of lymphocytes were observed with the help of transmission electron microscopy. MDV cooperating with REV promotes the course of disease of coinfection. Differential diagnosis can be done by immunohistochemistry in the early stage (before 2 weeks), and histopathology in the late stage (post 4 weeks). MDCs, primitive reticulum cells, immature lymphocytes, and two kinds of virions can serve as a basis for bistopathology differential diagnosis.展开更多
Marek’s disease (MD) is a lymphoproliferative disease of domestic chickens caused by Marek’s disease virus (MDV), an oncogenic and highly contagious α-herpesvirus. MD has been controlled by vaccination but sporadic...Marek’s disease (MD) is a lymphoproliferative disease of domestic chickens caused by Marek’s disease virus (MDV), an oncogenic and highly contagious α-herpesvirus. MD has been controlled by vaccination but sporadic outbreaks of MD still occur in some parts of the world. Efforts to improve vaccine efficacy have continued in both research communities and vaccine industries. We reported the host genetic variation affecting Marek’s disease vaccine-induced immunity in chickens earlier. In this study, we evaluated chicken lines, vaccines, and line by vaccine interaction on the protective efficacy of vaccination against MD. Specific pathogen free chickens from the relatively resistant line 63 and the highly susceptible line 72 were primarily used to evaluate the protection by three kinds of vaccines (rMd5ΔMeq, CVI988/Rispens, and HVT) upon challenge with a very virulent plus strain of MDV, vv+648A. Our data confirmed that both the chicken line and the vaccine significantly affected the protective efficacy of vaccination and showed that a chicken line by vaccine interaction, in most of the trials, also altered vaccine protective efficacy. More interestingly, although the protective index of all vaccine strains was higher in resistant than in susceptible line of chickens, the difference for HVT protection was striking and warrants further study. The findings may have important implications for vaccine development as well as for selective use of particular vaccines in specific lines of chickens to achieve maximum protection at minimized costs.展开更多
Isolation and identification of a specific cDNA mapping to the BamHI I2 and L fragments from the inverted repeats of unique long region(IRL) in the genome of Marek′s disease herpesvirus (MDV) oncogenic strain Beij...Isolation and identification of a specific cDNA mapping to the BamHI I2 and L fragments from the inverted repeats of unique long region(IRL) in the genome of Marek′s disease herpesvirus (MDV) oncogenic strain Beijing 1 had been previously performed by us. In this study, the specific cDNA was cloned into phagemid vectors PUC118 and 119 on the basis of prefabricated two recognized sites in synthesized primers. Recombinants were further identified with restriction pattern, molecular hybridization, and DNA sequencing analysis. It was demonstrated that this cDNA with 720 base pair (bp) contained sequences including a potentially incomplete open reading frame (ORF) encoded a 238 amino acids (aa) predicted polypeptide which was significantly homologous not only to part of N terminus of meq, but also to that of XbaI ClaI subfragment of BamHI L. In accordance with these data, following results could be deduced:①the 720 bp cDNA represented a spliced transcript;②meq transcription could be extended from the right hand end of BamHI I2 to the adjacent BamHI L fragment;③the L region was transcribed in varying degrees\ in MDV induced lymphoblastoid tumors.展开更多
Marek’s disease virus (MDV) challenge induces lymphoma in susceptible chickens. Host genes, especially immune related genes, are activated by the virus. DNA methylation is an epigenetic mechanism that governs gene tr...Marek’s disease virus (MDV) challenge induces lymphoma in susceptible chickens. Host genes, especially immune related genes, are activated by the virus. DNA methylation is an epigenetic mechanism that governs gene transcription. In the present study, we found that expression of signal transducer and activator of transcription 1 (STAT1) was upregulated at 10 days post infection (dpi) in MD susceptible chickens, whereas interleukin 12A (IL12A) was elevated in both resistant and susceptible chickens. However, we did not observe MDV-induced DNA methylation variations at the promoter CpG islands (CGIs) in STAT1 and IL12A. Interestingly, the methylation levels at Chicken Repeat 1 (CR1), the transposable elements (TEs) located upstream of two genes, were different between resistant and susceptible chickens. Furthermore, a mutation was identified in the CR1 element near IL12A. The impact of the point mutation in transcriptional factor binding is to be examined in the near future.展开更多
Interleukin-8 homolog (vIL-8) is a chemokine encoded by the genome of Marek's disease virus. Chicken IL-8 (cIL8) is an important chemokine of chickens which plays a role in antiviral activity. To explore the relat...Interleukin-8 homolog (vIL-8) is a chemokine encoded by the genome of Marek's disease virus. Chicken IL-8 (cIL8) is an important chemokine of chickens which plays a role in antiviral activity. To explore the relationship between vIL-8 and cIL8 can help to discern the function of vIL-8. In this study, the amino acid sequences of vIL-8 and cIL8 were aligned. The cIL8 gene was expressed in E. coli and the cIL8 fusion protein was obtained, after induction with IPTG. The protein was separated by SDS-PAGE and the band of interest was excised and minced for mouse immunization. An immunofluorescence test was used to detect vIL-8 expression in insect cells. The results showed that both vIL-8 and cIL8 were typical CXC chemokines in structure, and they had similar key amino acids, known to be important for receptor binding. The result of the immunofluorescence test showed that the mouse anti-cIL8 serum could react with vIL-8 expressed by insect cells. Therefore, vIL-8 shares common antigenic determinants with cIL8, and they may have a common receptor. This feature of vIL-8 suggests that it may participate in the immune evasion of the virus.展开更多
Five to ten serotyqe I Marek’s disease virus (MDV1) strains of different pathotypes were compared for their DNA sequences of gI, gE, pp38 and meq genes. The reference strains were vMDV GA and JM, vvMDV RB1B and Md11(...Five to ten serotyqe I Marek’s disease virus (MDV1) strains of different pathotypes were compared for their DNA sequences of gI, gE, pp38 and meq genes. The reference strains were vMDV GA and JM, vvMDV RB1B and Md11(p16), vv+MDV strains 648A and 584A,vaccine strain CVI988/Rispens; Chinese strains were: v MDV strain N, vvMDV strain G2, vaccine strain 814. Only random aa changes were found in 12 positions within gE of 497 aa among 10 analyzed strains and in 10 positions within gI of 355 aa among 5 strains. There was no relationship found between virus pathotypes and aa changes of both glycoproteins. The aa changes happened in 14 positions within meq of 339 aa among 5 compared strains. But a proline deletion at aa #194 in a proline-rich domain of meq were shared by two vaccine strains CVI988/Rispens and 814, the latter was a non-pathogenic vaccine strain of serotype 1 isolated in 1983 in China. In another hand, vv+MDV strains 648A demonstrated 5 unique aa changes and 4 of them also located in the proline-rich region. The pp38 was very conservative among sequenced 10 strains, there were only two positions at #107 and #109 with aa altered in its 290 aa. All tested MDV1 strains had glutamine at #107, instead, only vaccine CVI988 had arginine at the position and lost its epitope reactive with Mab H19, to which all other tested MDV1 strains were positive. However, CVI988 and vMDV GA shared a Mab T65-recognized epitope when there was glycine at aa#109. It was glutamic acid at aa#109 in all other MDV1 strains which were not reactive with Mab T65. It seems like that there is some relationship between pathotypes and sequences of pp38 and meq, but more strains need to be compared.展开更多
[Objective]To clone and identify Marek's disease virus ( MDV) serum gene. [Method]MDV genomic DNA was extracted from lymphoid tissues of the diseased chickens with latent MDV infection. The MDV L-meq gene was ampli...[Objective]To clone and identify Marek's disease virus ( MDV) serum gene. [Method]MDV genomic DNA was extracted from lymphoid tissues of the diseased chickens with latent MDV infection. The MDV L-meq gene was amplified by gradient PCR,inserted into pMD18-T vector and sequenced. The sequence was analyzed using DNAman software. [Result] The obtained sequence had 100% similarity with the published se- quence of L-meq gene,showing successful amplification of target gene. [Conclusion]The paper provides new ideas and new methods for preven- tion and treatment of Marek's disease in chickens.展开更多
Background:The selection of Marek’s disease(MD)-resistant breeds in Partridge Shank chicken,a popular local chicken breed in Henan Province of China,has practical value.We hypothesized that the two polymorphic sites(...Background:The selection of Marek’s disease(MD)-resistant breeds in Partridge Shank chicken,a popular local chicken breed in Henan Province of China,has practical value.We hypothesized that the two polymorphic sites(rs14527240 located in SMOC1 and GGaluGA156129 located in PTPN3)related to MD resistance in White Leghorn chickens are also applicable to Partridge Shank chickens.Methods:In this experiment,we screened 10 live hens and 2 live roosters with the double GG genotype by genotyping the two sites from 6500 Partridge Shank chickens.Nineteen one-day-old chicks with the double GG genotype were obtained by artificial insemination.Seventy-two one-day-old chickens(19 from the population expansion test and 53 randomly selected from chicken farms)were injected with 2000 plaque-forming units of the Md5 virus strain.After 100 days of infection,all chickens were examined by pathological anatomical examination,histological sectioning,genotyping,and a quantitative polymerase chain reaction of SMOC1 and PTPN3.Results:There was only one site(rs14527240 located in SMOC1)associated with MD in Partridge Shank chickens(p<0.05),but the GG genotype of SMOC1 in Partridge Shank chickens indicated susceptibility to MD.SMOC1 expression in MD-susceptible chickens was also significantly higher than that in MDresistant chickens(p<0.05).Conclusion:Therefore,the MD resistance sites selected from White Leghorn chickens were not completely suitable for Partridge Shank chickens,but they can be used as a reference.This study indicated that SMOC1 plays an important role in screening for MD resistance in poultry.展开更多
Common neurodegenerative diseases of the central nervous system are characterized by progressive damage to the function of neurons, even leading to the permanent loss of function. Gene therapy via gene replacement or ...Common neurodegenerative diseases of the central nervous system are characterized by progressive damage to the function of neurons, even leading to the permanent loss of function. Gene therapy via gene replacement or gene correction provides the potential for transformative therapies to delay or possibly stop further progression of the neurodegenerative disease in affected patients. Adeno-associated virus has been the vector of choice in recent clinical trials of therapies for neurodegenerative diseases due to its safety and efficiency in mediating gene transfer to the central nervous system. This review aims to discuss and summarize the progress and clinical applications of adeno-associated virus in neurodegenerative disease in central nervous system. Results from some clinical trials and successful cases of central neurodegenerative diseases deserve further study and exploration.展开更多
We present a case of a 19-year-old man with a 6-year history of Crohn's disease(CD), previously treated with 6-mercaptopurine, who was admitted to our department for Epstein-Barr virus(EBV) infection and subsequen...We present a case of a 19-year-old man with a 6-year history of Crohn's disease(CD), previously treated with 6-mercaptopurine, who was admitted to our department for Epstein-Barr virus(EBV) infection and subsequently developed a hemophagocytic lymphohistiocytosis(HLH). HLH is a rare disease which causes phagocytosis of all bone marrow derived cells. It can be a primary form as a autosomic recessive disease, or a secondary form associated with a variety of infections; EBV is the most common, the one with poorer prognosis. The incidence of lymphoproliferative disorders was increased in patients with inflammatory bowel disease(IBD) treated with thiopurines. Specific EBV-related clinical and virological management should be considered when treating a patient with IBD with immunosuppressive therapy. Moreover EBV infection in immunosuppressed patient can occur with more aggressive forms such as encephalitis and diffuse large B cell lymphoma. Our case confirms what is described in the literature; patients with IBD, particularly patients with CD receiving thiopurine therapy, who present 5 d of fever and cervical lymphadenopathy or previous evidence of lymphopenia should be screened for HLH.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
Intracranial delivery of human Fc-deleted antibody specific to amyloid-β peptide (Aβ, anti-Aβ single-chain Fv, scFv) via adeno-associated virus (AAV) inhibits amyloid deposition in transgenic mice. However, the...Intracranial delivery of human Fc-deleted antibody specific to amyloid-β peptide (Aβ, anti-Aβ single-chain Fv, scFv) via adeno-associated virus (AAV) inhibits amyloid deposition in transgenic mice. However, the effects of AAV-mediated Fc-deleted antibody on animal behavior remain unclear. In this study, the anti-Aβ scFv antibody gone, isolated from phage display, was fused to the 5' end of the scFv antibody gone for antibody secretion by 2 rounds of polymerase chain reaction amplification. The fused antibody cDNA was cloned into a pSNAV2 plasmid under the control of the cytomegalovirus promoter. The sequence verified expression vector pSNAV2/scFv was transferred to BHK-21 ceils, and stable transfected BHK-21/scFv cells were established by G418 selection and infected with the recombinant herpes simplex virus rHSV/repcap for AAV production. Recombinant AAV was injected into the left quadriceps femoris of PDAPP transgenic mice. After 3 months, Morris water-maze results confirmed significantly improved cognitive function in a mouse model of Alzheimer's disease. Key Words: Alzheimer's disease; adeno-associated virus; amyloid-β peptide; single-chain antibody; neurodegenerative diseases; neural regeneration展开更多
To investigate the dynamic change of heat shock protein 90 (Hsp90) in the genesis and development of tumor, we successfully established tumor animal model using Marek’s disease and then determined the location of H...To investigate the dynamic change of heat shock protein 90 (Hsp90) in the genesis and development of tumor, we successfully established tumor animal model using Marek’s disease and then determined the location of Hsp90 in the tumor tissue using immunohistochemistry method, the antibody titer level of Hsp90 in the serum and the expression level in the tissue using enzyme-linked immunosorbent assay (ELISA) method. Our result showed that Hsp90 location in the tumor tissue was signiifcantly associated with the tumor cell and most in the cytoplasm of the tumor cell, and Hsp90 expression level in the tissue and the antibody titer level in the serum was most signiifcantly increased with the development of tumor. This is the ifrst report to show the presence of Hsp90 in tumor tissues induced by the Marek’s disease, with its expression correlated to the tumoral grading. These data may also be valuable for developing new molecular anti-cancer therapies.展开更多
Marek’s disease(MD),a highly cell-associated and contagious disease of chickens caused by Marek’s disease virus(MDV)can result in neural lesions,immunosuppression and neoplasia in chicken.The Meq gene is an importan...Marek’s disease(MD),a highly cell-associated and contagious disease of chickens caused by Marek’s disease virus(MDV)can result in neural lesions,immunosuppression and neoplasia in chicken.The Meq gene is an important oncogene in the MDV genome,and it is expressed highly in MD tumor tissues and MD T-lymphoblastoid cell lines.An experiment was conducted to elucidate the role of Meq in MD tumor transformation.RNA interference technology was used to block its expression,and then analyzed the biological effects of Meq knockdown on the MD tumor cell line MSB1.A small interfering RNA with an interference efficiency of 70%(P<0.01)was transfected into MSB1 cells to knock down the expression of Meq gene.The cell proliferation,cycle and apoptosis were detected post-Meq knockdown.The results showed that MSB1 cell proliferation was downregulated remarkably at 48 h(P<0.01),60 h(P<0.05)and 72 h(P<0.01)post-Meq knockdown.The cell cycle was unaffected(P>0.05).B-cell lymphoma 2 gene(BCL2)was anti-apoptotic and caspase-6 was the effector in the apoptosis pathway.The activity of caspase-6 was upregulated(P<0.05)significantly and BCL2 gene expression was downregulated(P<0.05)significantly post-Meq knockdown,suggesting cell apoptosis might be induced.MSB1 cell migration did not exhibit any obvious change(P>0.05)post-Meq knockdown,but the expression of two genes(matrix metalloproteinase 2(MMP2)and MMP9)that are correlated closely to cell invasion was downregulated(P<0.05)remarkably post-Meq knockdown.The Meq knockdown might affect the main features of tumorous cells,including proliferation,apoptosis,and invasion,suggesting that the Meq gene might play a crucial role in interfering with lymphomatous cell transformation.展开更多
Background: Marek's disease(MD) is a highly contagious pathogenic and oncogenic disease primarily affecting chickens. However, the mechanisms of genetic resistance for MD are complex and not fully understood. MD-r...Background: Marek's disease(MD) is a highly contagious pathogenic and oncogenic disease primarily affecting chickens. However, the mechanisms of genetic resistance for MD are complex and not fully understood. MD-resistant line 6_3 and MD-susceptible line 7_2 are two highly inbred progenitor lines of White Leghorn. Recombinant Congenic Strains(RCS) were developed from these two lines, which show varied susceptibility to MD.Results: We investigated genetic structure and genomic signatures across the genome, including the line 6_3 and line7_2, six RCSs, and two reciprocally crossed flocks between the lines 6_3 and 7_2(F1 6_3× 7_2 and F1 7_2× 6_3) using Affymetrix~? Axiom~? HD 600 K genotyping array. We observed 18 chickens from RCS lines were specifically clustered into resistance sub-groups distributed around line 6_3. Additionally, homozygosity analysis was employed to explore potential genetic components related to MD resistance, while runs of homozygosity(ROH) are regions of the genome where the identical haplotypes are inherited from each parent. We found several genes including SIK, SOX1, LIG4, SIK1 and TNFSF13B were contained in ROH region identified in resistant group(line 6_3 and RCS), and these genes have been reported that are contribute to immunology and survival. Based on F_(ST) based population differential analysis, we also identified important genes related to cell death and anti-apoptosis, including AKT1, API5, CDH13, CFDP and USP15,which could be involved in divergent selection during inbreeding process.Conclusions: Our findings offer valuable insights for understanding the genetic mechanism of resistance to MD and the identified genes could be considered as candidate biomarkers in further evaluation.展开更多
Marek's disease(MD) is a lymphoproliferative disease of domestic chickens caused by a highly infectious,oncogenic alpha-herpesvirus known as Marek's disease virus(MDV).The aim of this study was to compare the ef...Marek's disease(MD) is a lymphoproliferative disease of domestic chickens caused by a highly infectious,oncogenic alpha-herpesvirus known as Marek's disease virus(MDV).The aim of this study was to compare the efficacy of four commercial MDV vaccines in Wenchang chicken.The 1-day old Wenchang chickens tested were injected with one of four different vaccines or not unvaccinated as control;five days later,they were then challenged by virulent MDV strain MD5.The results showed that,in comparison with HVT vaccines,the CVI988 vaccine gave the immunized chickens more potent immunities against challenges of MDV strain MD5.展开更多
基金Supported by the National High Level Hospital Clinical Research Funding,No.2022-PUMCH-A-017 and No.2022-PUMCH-B-045CAMS Innovation Fund for Medical Sciences from Chinese Academy of Medical Sciences,No.2021-I2M-1-062.
文摘BACKGROUND Acute acalculous cholecystitis(AAC)is inflammation of the gallbladder without evidence of calculi.Although rarely reported,its etiologies include hepatitis virus infection(e.g.,hepatitis A virus,HAV)and adult-onset Still’s disease(AOSD).There are no reports of HAV-associated AAC in an AOSD patient.CASE SUMMARY Here we report a rare case of HAV infection-associated AAC in a 39-year-old woman who had a history of AOSD.The patient presented with an acute abdomen and hypotension.Elevated hepatobiliary enzymes and a thickened and distended gallbladder without gallstones on ultrasonography suggested AAC,but there were no signs of anemia nor thrombocytopenia.Serological screening revealed anti-HAV IgM antibodies.Steroid treatment did not alleviate her symptoms,and she was referred for laparoscopic cholecystectomy.The resected gallbladder was hydropic without perforation,and her clinical signs gradually improved after surgery.CONCLUSION AAC can be caused by HAV in AOSD patients.It is crucial to search for the underlying etiology for AAC,especially uncommon viral causes.
基金Supported by Clinical and Translational Medicine Research Foundation of Chinese Academy of Medical Sciences,No. 2020-I2M-C&T-B-038Capital Health Research and Development of Special Project,No. 2022-1-2181Group Medical Aid Project of the Tibet Autonomous Region Natural Science Foundation,No. XZ2020ZR-ZY28[Z]
文摘BACKGROUND Emerging studies indicate the critical involvement of microorganisms,such as Epstein-Barr virus(EBV),in the pathogenesis of inflammatory bowel disease(IBD).Immunosuppressive therapies for IBD can reactivate latent EBV,complicating the clinical course of IBD.Moreover,the clinical significance of EBV expression in B lymphocytes derived from IBD patients’intestinal tissues has not been explored in detail.AIM To explore the clinical significance of latent EBV infection in IBD patients.METHODS Latent EBV infection was determined by double staining for EBV encoded RNA and CD20 in colon specimens of 43 IBD patients who underwent bowel resection.Based on the staining results,the patients were divided into two groups,according to their latent EBV infection states-negative(n=33)and positive(n=10).Illness severity of IBD were assigned according to Crohn’s disease activity index(ulcerative colitis)and Mayo staging system(Crohn’s disease).The clinicpathological data were analyzed between the two different latent EBV groups and also between the mild-to-moderate and severe disease groups.RESULTS Systolic pressure(P=0.005),variety of disease(P=0.005),the severity of illness(P=0.002),and pre-op corticosteroids(P=0.025)were significantly different between the EBV-negative and EBV-positive groups.Systolic pressure(P=0.001),variety of disease(P=0.000),pre-op corticosteroids(P=0.011)and EBV infection(P=0.003)were significantly different between the mild-to-moderate and severe disease groups.CONCLUSION IBD patients with latent EBV infection may manifest more severe illnesses.It is suggested that the role of EBV in IBD development should be further investigated,latent EBV infection in patients with serious IBD should be closely monitored,and therapeutic course should be optimized.
文摘BACKGROUND Inflammatory bowel disease(IBD)is an autoimmune condition treated with immunosuppressive drugs.However,the need for immune system suppression becomes questionable when infection with the human immunodeficiency virus(HIV)occurs simultaneously and impacts the course of IBD.Our reported case represents the clinical course,prescribed treatment and its effect,as well as clinical challenges faced by physicians in a combination of such diseases.We also present a comprehensive literature review of similar cases.CASE SUMMARY A 49-year-old woman suffering from a newly diagnosed Crohn’s disease was hospitalized due to exacerbated symptoms(abdominal pain,fever,and weight loss).During her hospital stay,she tested positive for HIV.With conservative treatment,the patient improved and was discharged.In the outpatient clinic,her HIV infection was confirmed as stage C3,and antiretroviral treatment was initiated immediately.That notwithstanding,soon the patient was rehospitalized with pulmonary embolism and developed a series of complications because of the subsequent coexistence of IBD and HIV.After intensive and meticulous treatment,the patient’s condition has improved and she remains in remission.CONCLUSION The paucity of studies and data on the coexistence of HIV and IBD leaves clinicians doubting the optimal treatment options.
基金supported by grants from the National Science Foundation for Post-Doctoral of China(2005038258)
文摘To further understand the generation and development of coinfection of Marek's disease virus (MDV) and reticuloendotheliosis virus (REV) in broiler breeders, and then find the method and optimal time of differential diagnosis for complex clinic multiple infection, the authors studied the pathohistological changes, apoptosis, immunohistochemistry (immunofluorescence), and ultrastructure of tumor tissues of broiler breeders inoculated with MDV and REV. The study showed that proliferation of small lymphocytes was seen in the main organs at the age of 1 week, then immature lymphocytes, all kinds of lymphocytes, primitive reticulum cells, and Marek's disease cells (MDCs) were observed at 2-9 weeks. Apoptosis of lymphocytes could not be seen until the age of 10 weeks in the immune system. Immunohistochemistry detection showed that the positive signs of MDV and REV antigen were observed in the main organs at 2 weeks of age. Multi-morphology lymphocytes, MDV, and REV, mitotic figures and apoptosis of lymphocytes were observed with the help of transmission electron microscopy. MDV cooperating with REV promotes the course of disease of coinfection. Differential diagnosis can be done by immunohistochemistry in the early stage (before 2 weeks), and histopathology in the late stage (post 4 weeks). MDCs, primitive reticulum cells, immature lymphocytes, and two kinds of virions can serve as a basis for bistopathology differential diagnosis.
文摘Marek’s disease (MD) is a lymphoproliferative disease of domestic chickens caused by Marek’s disease virus (MDV), an oncogenic and highly contagious α-herpesvirus. MD has been controlled by vaccination but sporadic outbreaks of MD still occur in some parts of the world. Efforts to improve vaccine efficacy have continued in both research communities and vaccine industries. We reported the host genetic variation affecting Marek’s disease vaccine-induced immunity in chickens earlier. In this study, we evaluated chicken lines, vaccines, and line by vaccine interaction on the protective efficacy of vaccination against MD. Specific pathogen free chickens from the relatively resistant line 63 and the highly susceptible line 72 were primarily used to evaluate the protection by three kinds of vaccines (rMd5ΔMeq, CVI988/Rispens, and HVT) upon challenge with a very virulent plus strain of MDV, vv+648A. Our data confirmed that both the chicken line and the vaccine significantly affected the protective efficacy of vaccination and showed that a chicken line by vaccine interaction, in most of the trials, also altered vaccine protective efficacy. More interestingly, although the protective index of all vaccine strains was higher in resistant than in susceptible line of chickens, the difference for HVT protection was striking and warrants further study. The findings may have important implications for vaccine development as well as for selective use of particular vaccines in specific lines of chickens to achieve maximum protection at minimized costs.
文摘Isolation and identification of a specific cDNA mapping to the BamHI I2 and L fragments from the inverted repeats of unique long region(IRL) in the genome of Marek′s disease herpesvirus (MDV) oncogenic strain Beijing 1 had been previously performed by us. In this study, the specific cDNA was cloned into phagemid vectors PUC118 and 119 on the basis of prefabricated two recognized sites in synthesized primers. Recombinants were further identified with restriction pattern, molecular hybridization, and DNA sequencing analysis. It was demonstrated that this cDNA with 720 base pair (bp) contained sequences including a potentially incomplete open reading frame (ORF) encoded a 238 amino acids (aa) predicted polypeptide which was significantly homologous not only to part of N terminus of meq, but also to that of XbaI ClaI subfragment of BamHI L. In accordance with these data, following results could be deduced:①the 720 bp cDNA represented a spliced transcript;②meq transcription could be extended from the right hand end of BamHI I2 to the adjacent BamHI L fragment;③the L region was transcribed in varying degrees\ in MDV induced lymphoblastoid tumors.
文摘Marek’s disease virus (MDV) challenge induces lymphoma in susceptible chickens. Host genes, especially immune related genes, are activated by the virus. DNA methylation is an epigenetic mechanism that governs gene transcription. In the present study, we found that expression of signal transducer and activator of transcription 1 (STAT1) was upregulated at 10 days post infection (dpi) in MD susceptible chickens, whereas interleukin 12A (IL12A) was elevated in both resistant and susceptible chickens. However, we did not observe MDV-induced DNA methylation variations at the promoter CpG islands (CGIs) in STAT1 and IL12A. Interestingly, the methylation levels at Chicken Repeat 1 (CR1), the transposable elements (TEs) located upstream of two genes, were different between resistant and susceptible chickens. Furthermore, a mutation was identified in the CR1 element near IL12A. The impact of the point mutation in transcriptional factor binding is to be examined in the near future.
基金funded by Program for Changjiang Scholars and Innovative Research Team in University(IRT0978,PCSIRT)the National Natural Science Foundation of China(30270982)
文摘Interleukin-8 homolog (vIL-8) is a chemokine encoded by the genome of Marek's disease virus. Chicken IL-8 (cIL8) is an important chemokine of chickens which plays a role in antiviral activity. To explore the relationship between vIL-8 and cIL8 can help to discern the function of vIL-8. In this study, the amino acid sequences of vIL-8 and cIL8 were aligned. The cIL8 gene was expressed in E. coli and the cIL8 fusion protein was obtained, after induction with IPTG. The protein was separated by SDS-PAGE and the band of interest was excised and minced for mouse immunization. An immunofluorescence test was used to detect vIL-8 expression in insect cells. The results showed that both vIL-8 and cIL8 were typical CXC chemokines in structure, and they had similar key amino acids, known to be important for receptor binding. The result of the immunofluorescence test showed that the mouse anti-cIL8 serum could react with vIL-8 expressed by insect cells. Therefore, vIL-8 shares common antigenic determinants with cIL8, and they may have a common receptor. This feature of vIL-8 suggests that it may participate in the immune evasion of the virus.
文摘Five to ten serotyqe I Marek’s disease virus (MDV1) strains of different pathotypes were compared for their DNA sequences of gI, gE, pp38 and meq genes. The reference strains were vMDV GA and JM, vvMDV RB1B and Md11(p16), vv+MDV strains 648A and 584A,vaccine strain CVI988/Rispens; Chinese strains were: v MDV strain N, vvMDV strain G2, vaccine strain 814. Only random aa changes were found in 12 positions within gE of 497 aa among 10 analyzed strains and in 10 positions within gI of 355 aa among 5 strains. There was no relationship found between virus pathotypes and aa changes of both glycoproteins. The aa changes happened in 14 positions within meq of 339 aa among 5 compared strains. But a proline deletion at aa #194 in a proline-rich domain of meq were shared by two vaccine strains CVI988/Rispens and 814, the latter was a non-pathogenic vaccine strain of serotype 1 isolated in 1983 in China. In another hand, vv+MDV strains 648A demonstrated 5 unique aa changes and 4 of them also located in the proline-rich region. The pp38 was very conservative among sequenced 10 strains, there were only two positions at #107 and #109 with aa altered in its 290 aa. All tested MDV1 strains had glutamine at #107, instead, only vaccine CVI988 had arginine at the position and lost its epitope reactive with Mab H19, to which all other tested MDV1 strains were positive. However, CVI988 and vMDV GA shared a Mab T65-recognized epitope when there was glycine at aa#109. It was glutamic acid at aa#109 in all other MDV1 strains which were not reactive with Mab T65. It seems like that there is some relationship between pathotypes and sequences of pp38 and meq, but more strains need to be compared.
基金funded by the grants of Jilin Provincial Department of Education (2010 No. 382)Natural Science Foundation of Changchun Normal University (2010 No. 023)
文摘[Objective]To clone and identify Marek's disease virus ( MDV) serum gene. [Method]MDV genomic DNA was extracted from lymphoid tissues of the diseased chickens with latent MDV infection. The MDV L-meq gene was amplified by gradient PCR,inserted into pMD18-T vector and sequenced. The sequence was analyzed using DNAman software. [Result] The obtained sequence had 100% similarity with the published se- quence of L-meq gene,showing successful amplification of target gene. [Conclusion]The paper provides new ideas and new methods for preven- tion and treatment of Marek's disease in chickens.
基金supported by grants from Key Research Project of the Shennong Laboratory(Grant Number SN01-2022-05)the Tackling Key Projects in Science and Technology in Henan Province(Grant Number 162102110039)the Independent Innovation Project of Henan Academy of Agricultural Sciences(Grant Number 2022ZC46).
文摘Background:The selection of Marek’s disease(MD)-resistant breeds in Partridge Shank chicken,a popular local chicken breed in Henan Province of China,has practical value.We hypothesized that the two polymorphic sites(rs14527240 located in SMOC1 and GGaluGA156129 located in PTPN3)related to MD resistance in White Leghorn chickens are also applicable to Partridge Shank chickens.Methods:In this experiment,we screened 10 live hens and 2 live roosters with the double GG genotype by genotyping the two sites from 6500 Partridge Shank chickens.Nineteen one-day-old chicks with the double GG genotype were obtained by artificial insemination.Seventy-two one-day-old chickens(19 from the population expansion test and 53 randomly selected from chicken farms)were injected with 2000 plaque-forming units of the Md5 virus strain.After 100 days of infection,all chickens were examined by pathological anatomical examination,histological sectioning,genotyping,and a quantitative polymerase chain reaction of SMOC1 and PTPN3.Results:There was only one site(rs14527240 located in SMOC1)associated with MD in Partridge Shank chickens(p<0.05),but the GG genotype of SMOC1 in Partridge Shank chickens indicated susceptibility to MD.SMOC1 expression in MD-susceptible chickens was also significantly higher than that in MDresistant chickens(p<0.05).Conclusion:Therefore,the MD resistance sites selected from White Leghorn chickens were not completely suitable for Partridge Shank chickens,but they can be used as a reference.This study indicated that SMOC1 plays an important role in screening for MD resistance in poultry.
文摘Common neurodegenerative diseases of the central nervous system are characterized by progressive damage to the function of neurons, even leading to the permanent loss of function. Gene therapy via gene replacement or gene correction provides the potential for transformative therapies to delay or possibly stop further progression of the neurodegenerative disease in affected patients. Adeno-associated virus has been the vector of choice in recent clinical trials of therapies for neurodegenerative diseases due to its safety and efficiency in mediating gene transfer to the central nervous system. This review aims to discuss and summarize the progress and clinical applications of adeno-associated virus in neurodegenerative disease in central nervous system. Results from some clinical trials and successful cases of central neurodegenerative diseases deserve further study and exploration.
文摘We present a case of a 19-year-old man with a 6-year history of Crohn's disease(CD), previously treated with 6-mercaptopurine, who was admitted to our department for Epstein-Barr virus(EBV) infection and subsequently developed a hemophagocytic lymphohistiocytosis(HLH). HLH is a rare disease which causes phagocytosis of all bone marrow derived cells. It can be a primary form as a autosomic recessive disease, or a secondary form associated with a variety of infections; EBV is the most common, the one with poorer prognosis. The incidence of lymphoproliferative disorders was increased in patients with inflammatory bowel disease(IBD) treated with thiopurines. Specific EBV-related clinical and virological management should be considered when treating a patient with IBD with immunosuppressive therapy. Moreover EBV infection in immunosuppressed patient can occur with more aggressive forms such as encephalitis and diffuse large B cell lymphoma. Our case confirms what is described in the literature; patients with IBD, particularly patients with CD receiving thiopurine therapy, who present 5 d of fever and cervical lymphadenopathy or previous evidence of lymphopenia should be screened for HLH.
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.
基金the National Natural Science Foundation of China,No. 30670741
文摘Intracranial delivery of human Fc-deleted antibody specific to amyloid-β peptide (Aβ, anti-Aβ single-chain Fv, scFv) via adeno-associated virus (AAV) inhibits amyloid deposition in transgenic mice. However, the effects of AAV-mediated Fc-deleted antibody on animal behavior remain unclear. In this study, the anti-Aβ scFv antibody gone, isolated from phage display, was fused to the 5' end of the scFv antibody gone for antibody secretion by 2 rounds of polymerase chain reaction amplification. The fused antibody cDNA was cloned into a pSNAV2 plasmid under the control of the cytomegalovirus promoter. The sequence verified expression vector pSNAV2/scFv was transferred to BHK-21 ceils, and stable transfected BHK-21/scFv cells were established by G418 selection and infected with the recombinant herpes simplex virus rHSV/repcap for AAV production. Recombinant AAV was injected into the left quadriceps femoris of PDAPP transgenic mice. After 3 months, Morris water-maze results confirmed significantly improved cognitive function in a mouse model of Alzheimer's disease. Key Words: Alzheimer's disease; adeno-associated virus; amyloid-β peptide; single-chain antibody; neurodegenerative diseases; neural regeneration
基金supported by the National Natural Science Foundation of China (31101787)the Natural Science Foundation of Shandong Province,China (ZR2010CM035)
文摘To investigate the dynamic change of heat shock protein 90 (Hsp90) in the genesis and development of tumor, we successfully established tumor animal model using Marek’s disease and then determined the location of Hsp90 in the tumor tissue using immunohistochemistry method, the antibody titer level of Hsp90 in the serum and the expression level in the tissue using enzyme-linked immunosorbent assay (ELISA) method. Our result showed that Hsp90 location in the tumor tissue was signiifcantly associated with the tumor cell and most in the cytoplasm of the tumor cell, and Hsp90 expression level in the tissue and the antibody titer level in the serum was most signiifcantly increased with the development of tumor. This is the ifrst report to show the presence of Hsp90 in tumor tissues induced by the Marek’s disease, with its expression correlated to the tumoral grading. These data may also be valuable for developing new molecular anti-cancer therapies.
基金The work was supported in part by the National Natural Science Foundation of China(31320103905 and U1901206)the Young Scientist Supporting Project,Program for Changjiang Scholars and Innovative Research Team in University(IRT_15R62)+6 种基金the earmarked fund for China Agriculture Research Systems(CARS-41)the National High Technology Development Plan of China(2013AA102501)the Farm Animals Germplasm Resource Bankthe Beijing Key Laboratory for Animal Genetic Improvement,the University Research Project of Anhui Province,China(KJ2020A0081)the Anhui Provincial Natural Science Foundation,China(2008085QC140)the Foundation of Anhui Science and Technology University,China(DKYJ201901)the Innovation Funds for Undergraduate Students of Anhui Province,China(S201910879019,S202010879109,and S202010879120).
文摘Marek’s disease(MD),a highly cell-associated and contagious disease of chickens caused by Marek’s disease virus(MDV)can result in neural lesions,immunosuppression and neoplasia in chicken.The Meq gene is an important oncogene in the MDV genome,and it is expressed highly in MD tumor tissues and MD T-lymphoblastoid cell lines.An experiment was conducted to elucidate the role of Meq in MD tumor transformation.RNA interference technology was used to block its expression,and then analyzed the biological effects of Meq knockdown on the MD tumor cell line MSB1.A small interfering RNA with an interference efficiency of 70%(P<0.01)was transfected into MSB1 cells to knock down the expression of Meq gene.The cell proliferation,cycle and apoptosis were detected post-Meq knockdown.The results showed that MSB1 cell proliferation was downregulated remarkably at 48 h(P<0.01),60 h(P<0.05)and 72 h(P<0.01)post-Meq knockdown.The cell cycle was unaffected(P>0.05).B-cell lymphoma 2 gene(BCL2)was anti-apoptotic and caspase-6 was the effector in the apoptosis pathway.The activity of caspase-6 was upregulated(P<0.05)significantly and BCL2 gene expression was downregulated(P<0.05)significantly post-Meq knockdown,suggesting cell apoptosis might be induced.MSB1 cell migration did not exhibit any obvious change(P>0.05)post-Meq knockdown,but the expression of two genes(matrix metalloproteinase 2(MMP2)and MMP9)that are correlated closely to cell invasion was downregulated(P<0.05)remarkably post-Meq knockdown.The Meq knockdown might affect the main features of tumorous cells,including proliferation,apoptosis,and invasion,suggesting that the Meq gene might play a crucial role in interfering with lymphomatous cell transformation.
基金supported in part by U.S.Department of Agriculture(USDA)-Nation Research Initiative/National Institute of Food and Agriculture(NRI/NIFA)2008–35204-04660,2010–65205-20588 and 2011–67015-30183
文摘Background: Marek's disease(MD) is a highly contagious pathogenic and oncogenic disease primarily affecting chickens. However, the mechanisms of genetic resistance for MD are complex and not fully understood. MD-resistant line 6_3 and MD-susceptible line 7_2 are two highly inbred progenitor lines of White Leghorn. Recombinant Congenic Strains(RCS) were developed from these two lines, which show varied susceptibility to MD.Results: We investigated genetic structure and genomic signatures across the genome, including the line 6_3 and line7_2, six RCSs, and two reciprocally crossed flocks between the lines 6_3 and 7_2(F1 6_3× 7_2 and F1 7_2× 6_3) using Affymetrix~? Axiom~? HD 600 K genotyping array. We observed 18 chickens from RCS lines were specifically clustered into resistance sub-groups distributed around line 6_3. Additionally, homozygosity analysis was employed to explore potential genetic components related to MD resistance, while runs of homozygosity(ROH) are regions of the genome where the identical haplotypes are inherited from each parent. We found several genes including SIK, SOX1, LIG4, SIK1 and TNFSF13B were contained in ROH region identified in resistant group(line 6_3 and RCS), and these genes have been reported that are contribute to immunology and survival. Based on F_(ST) based population differential analysis, we also identified important genes related to cell death and anti-apoptosis, including AKT1, API5, CDH13, CFDP and USP15,which could be involved in divergent selection during inbreeding process.Conclusions: Our findings offer valuable insights for understanding the genetic mechanism of resistance to MD and the identified genes could be considered as candidate biomarkers in further evaluation.
基金Supported by Hainan Provincial Key Science and Technology Project(ZDXM20100029)China Agriculture Research System(CARS-42)
文摘Marek's disease(MD) is a lymphoproliferative disease of domestic chickens caused by a highly infectious,oncogenic alpha-herpesvirus known as Marek's disease virus(MDV).The aim of this study was to compare the efficacy of four commercial MDV vaccines in Wenchang chicken.The 1-day old Wenchang chickens tested were injected with one of four different vaccines or not unvaccinated as control;five days later,they were then challenged by virulent MDV strain MD5.The results showed that,in comparison with HVT vaccines,the CVI988 vaccine gave the immunized chickens more potent immunities against challenges of MDV strain MD5.