Hepatitis B virus(HBV)reactivation is a clinically significant challenge in disease management.This review explores the immunological mechanisms underlying HBV reactivation,emphasizing disease progression and manageme...Hepatitis B virus(HBV)reactivation is a clinically significant challenge in disease management.This review explores the immunological mechanisms underlying HBV reactivation,emphasizing disease progression and management.It delves into host immune responses and reactivation’s delicate balance,spanning innate and adaptive immunity.Viral factors’disruption of this balance,as are interac-tions between viral antigens,immune cells,cytokine networks,and immune checkpoint pathways,are examined.Notably,the roles of T cells,natural killer cells,and antigen-presenting cells are discussed,highlighting their influence on disease progression.HBV reactivation’s impact on disease severity,hepatic flares,liver fibrosis progression,and hepatocellular carcinoma is detailed.Management strategies,including anti-viral and immunomodulatory approaches,are critically analyzed.The role of prophylactic anti-viral therapy during immunosuppressive treatments is explored alongside novel immunotherapeutic interventions to restore immune control and prevent reactivation.In conclusion,this compre-hensive review furnishes a holistic view of the immunological mechanisms that propel HBV reactivation.With a dedicated focus on understanding its implic-ations for disease progression and the prospects of efficient management stra-tegies,this article contributes significantly to the knowledge base.The more profound insights into the intricate interactions between viral elements and the immune system will inform evidence-based approaches,ultimately enhancing disease management and elevating patient outcomes.The dynamic landscape of management strategies is critically scrutinized,spanning anti-viral and immunomodulatory approaches.The role of prophylactic anti-viral therapy in preventing reactivation during immunosuppressive treatments and the potential of innovative immunotherapeutic interventions to restore immune control and proactively deter reactivation.展开更多
AIM: To evaluate whether intratumoral expression of measles virus fusogenic membrane glycoproteins H and F (MV-FMG), encoded by an adenovirus vector Ad.MV-HI F, alone or in combination with local coexpression of cy...AIM: To evaluate whether intratumoral expression of measles virus fusogenic membrane glycoproteins H and F (MV-FMG), encoded by an adenovirus vector Ad.MV-HI F, alone or in combination with local coexpression of cytokines (IL-2, IL-12, IL-18, IL-21 or GM-CSF), can serve as a platform for inducing tumor-specific immune responses in colon cancer.METHODS: We used confocal laser scanning microscopy and flow cytometry to analyze cell-cell fusion after expression of MV-FMG by dye colocalization. In a syngeneic bilateral subcutaneous MC38 and Colon26 colon cancer model in C57BL/6 and BALB/c mice, we assessed the effect on both the directly vector-treated tumor as well as the contralateral, not directly vector- treated tumor. We assessed the induction of a tumorspecific cytotoxic T lymphocyte (CTL) response with a lactate dehydrogenase (LDH) release assay.RESULTS: We demonstrated in vitro that transduction of MC38 and Colon26 cells with Ad.MV-H/F resulted in dye colocalization, indicative of cell-cell fusion, in addition, in the syngeneic bilateral tumor model we demonstrated a significant regression of the directly vector-inoculated tumor upon intratumoral expression of MV-FMG alone or in combination with the tested cytokines. We observed the highest anti-neoplastic efficacy with MV-FMG and lL-21 coexpression. The degree of tumor regression of the not directly vector-treated tumor correlated with the anti-neoplastic response of the directly vector-treated tumor. This regression was mediated by a tumor-specific CTL response.CONCLUSION: Our data indicate that intratumoral expression of measles virus fusogenic membrane glycoproteins is a promising tool both for direct tumor treatment as well as for tumor vaccination approaches that can be further enhanced by cytokine coexpression.展开更多
Hemagglutinin gene of Measles virus(Nepal strain) was amplified by RT PCR technique, cloned and sequenced by the dideoxy mediated chain termination method. The comparison to the standard strain(Edmonston strain) sho...Hemagglutinin gene of Measles virus(Nepal strain) was amplified by RT PCR technique, cloned and sequenced by the dideoxy mediated chain termination method. The comparison to the standard strain(Edmonston strain) showed many important mutations. The homology of these two strains was 98.17%. Then H gene was cloned into expression vector pCD SRα296 and introduced into COS 7 cells by electroporation method. The expression and function of cloned H gene was checked by hemadsorption assays.展开更多
The complete nucleotide sequence of the measles virus strain IMB-1,which was isolated in China,was determined.As in other measles viruses,its genome is 15,894 nucleotides in length and encodes six proteins.The full-le...The complete nucleotide sequence of the measles virus strain IMB-1,which was isolated in China,was determined.As in other measles viruses,its genome is 15,894 nucleotides in length and encodes six proteins.The full-length nucleotide sequence of the IMB-1 isolate differed from vaccine strains (including wild-type Edmonston strain) by 4%-5% at the nucleotide sequence level.This isolate has amino acid variations over the full genome,including in the hemagglutinin and fusion genes.This report is the first to describe the full-length genome of a genotype H1 strain and provide an overview of the diversity of genetic characteristics of a circulating measles virus.展开更多
[Objective] The aim of this study was to realize efficient expression of the porcine reproductive and respiratory syndrome virus (PRRSV) ORF7 gene in genetic engineering bacteria and analYze the immunological activi...[Objective] The aim of this study was to realize efficient expression of the porcine reproductive and respiratory syndrome virus (PRRSV) ORF7 gene in genetic engineering bacteria and analYze the immunological activity of the recombinant protein after purification. [ Method] The constructed recombinant expression vector pET-ORF7 was transformed into Escherichia co1BL21 (DE3) and induced by IPTG under the optimal condition. After analysis of SDS-PAGE and Western Blot, the expression products were purified by Ni-NTA His · Bind Resin chrom- atographic column under denaturing condition and renatured by gradient dialysis. Subsequently, the immunological activity of the renatured recombinant protein was detected by Westem Blot and indirect ELISA. [ Result] The recombinant plasmid pET-ORF7 expressed in E. coli successfully, and the fusion protein was in the form of inclusion body. By SDS-PAGE detection, the molecular weight of the expression protein was approximate 33 kD, according with the expectation. Analysis by Bandscan software showed that the expressed fusion protein was about 50% of total bacterial protein of BL21 (DE3). Wastem Blot and indirect ELISA detection showed that the renatured protein could react with PRRSV positive serum specifically, indicating its good immunological activity. [ Conclusion] This study lays a foundation for the preparation of PRRSV monoclonal antibody and diagnostic kit.展开更多
Hepatitis C virus (HCV) has been recognized to be both a hepato- and lymphotropic virus. HCV lymphotropism represents an essential lap in the pathogenesis of virus-related autoimmune and lymphoproliferative disorder...Hepatitis C virus (HCV) has been recognized to be both a hepato- and lymphotropic virus. HCV lymphotropism represents an essential lap in the pathogenesis of virus-related autoimmune and lymphoproliferative disorders, ranging from clonal expansion of B-cells with organ-and non-organ-specific autoantibody production up to overt non-Hodgkin's lymphoma along a continuous step-by-step model of B-cell lymphomagenesis, where the intermediated mixed cryoglobulinemia could be considered as a stage of suppressible antigen-driven lymphoproliferation. HCV infection of lymphoid ceils could set up privileged reservoirs able to interfere with the host viral clearance efficiency and may be implicated in viral recurrence after apparently successful antiviral therapy. The HCV long-lasting extrahepatic replicative state generates an abnormal systemic immunological response, easily detectable by searching simple laboratory and clinical parameters, mainly represented by vasculitis-like skin features and hypocomplementemia.The presence or absence of this hypersensitivity pattern seems to correlate with the antiviral response and could be identified as a novel immunological cofactor. Further research is required to fully verify the real impact on therapeutic choice/regimen.展开更多
BACKGROUND Hepatitis B virus(HBV)infection is a major factor responsible for HBV+hepatocellular carcinoma(HCC).AIM An immunological classification of HBV+HCC may provide both biological insights and clinical implicati...BACKGROUND Hepatitis B virus(HBV)infection is a major factor responsible for HBV+hepatocellular carcinoma(HCC).AIM An immunological classification of HBV+HCC may provide both biological insights and clinical implications for this disease.METHODS Based on the enrichment of 23 immune signatures,we identified two immunespecific subtypes(Imm-H and Imm-L)of HBV+HCC by unsupervised clustering.We showed that this subtyping method was reproducible and predictable by analyzing three different datasets.RESULTS Compared to Imm-L,Imm-H displayed stronger immunity,more stromal components,lower tumor purity,lower stemness and intratumor heterogeneity,lower-level copy number alterations,higher global methylation level,and better overall and disease-free survival prognosis.Besides immune-related pathways,stromal pathways(ECM receptor interaction,focal adhesion,and regulation of actin cytoskeleton)and neuro-related pathways(neuroactive ligand-receptor interaction,and prion diseases)were more highly enriched in Imm-H than in Imm-L.We identified nine proteins differentially expressed between Imm-H and Imm-L,of which MYH11,PDCD4,Dvl3,and Syk were upregulated in Imm-H,while PCNA,Acetyl-a-Tubulin-Lys40,ER-α_pS118,Cyclin E2,andβ-Catenin were upregulated in Imm-L.CONCLUSION Our data suggest that“hot”tumors have a better prognosis than“cold”tumors in HBV+HCC and that“hot”tumors respond better to immunotherapy.展开更多
The experiment was conducted to inoculate one-day old chicks with March's disease (MD) trivalent and herpesvirus of turkey (HVT) vaccines separately, and then to challenge them with virulent MD virus (vMDV) at the...The experiment was conducted to inoculate one-day old chicks with March's disease (MD) trivalent and herpesvirus of turkey (HVT) vaccines separately, and then to challenge them with virulent MD virus (vMDV) at the age of 15 days. and 5, 25, 45 and 75 days after the challenge with vMDV, comparing with the control-challenged chicks without immunization, to detect the immunoprotetive efficacy and dynamic changes of the inductive activity of interleukin-2(IL-2), expression of IL-2 receptor and proliferative function of T cells in thymus and spleen; the number of ANAE+T, AP+T cells and IgG, IgM, IgA antibody-producing cells in Bursa Fabricius, spleen,thymus, cecal tonsil and Harder gland; as the amount of T cells and IgG, IgM, IgA in peripheral blood as well as the content of IgG, IgM and IgA in the tear, trachea washings, bile and intestinal fluids of the experimental chicks. The experimental results firstly demonstrate that the immunorcgulation of IL-2, and IL-2 receptor, the cellualr and humoral immune responses were significantly enhanced in the central and peripheral immune organs; the local mucosal immune function were markedly amplified in the respiratory and digestive tracts of the immunized-challenged,chicks, which were closely correlated with the immunoprotection against MD; the immune response and immunoprotective effect of the trivalent vaccine-immunized chicks were much better than those of HVT vaccine-immunized chicks:展开更多
Type I interferons are critical antiviral cytokines produced following herpes simplex virus type-1 (HSV-1) infection that act to inhibit viral spread. In the present study, we identify HSV-infected and adjacent unin...Type I interferons are critical antiviral cytokines produced following herpes simplex virus type-1 (HSV-1) infection that act to inhibit viral spread. In the present study, we identify HSV-infected and adjacent uninfected corneal epithelial cells as the source of interferon-a. We also report mice deficient in the A1 chain of the type I IFN receptor (CDl18-/) are extremely sensitive to ocular infection with low doses (100 PFU) of HSV-1 as seen by significantly elevated viral titers in the cornea Compared to wild type (WT) controls. The enhanced susceptibil- ity correlated with a loss of CD4+ and CD8+ T cell recruitment and aberrant chemokine production in the cornea despite mounting an adaptive immune response in the draining mandibular lymph node of CDll8/ mice. Taken together, these results highlight the importance of IFN production in both the innate immune response as well as eliciting chemokine production required to facilitate adaptive immune cell trafficking.展开更多
It has been reported that the direct binding of hepatitis C virus(HCV)and/or the replication of HCV in the extrahepatic organs and,especially,lymphoid cells,might affect the pathogenesis of extrahepatic diseases with ...It has been reported that the direct binding of hepatitis C virus(HCV)and/or the replication of HCV in the extrahepatic organs and,especially,lymphoid cells,might affect the pathogenesis of extrahepatic diseases with HCV infection.More than one decade ago,several reports described the existence of HCV-RNA in peripheral blood mononuclear cells.Moreover,many reports describing the existence of HCV in B lymphocytes and B cell lymphoma have been published.In addition to B lymphocytes,it was reported that HCV replication could be detected in T lymphocytes and T cell lines.Among the extrahepatic diseases with HCV infection,mixed cryoglobulinemia-related diseases and autoimmunerelated diseases are important for understanding the immunopathogensis of HCV persistent infection.Moreover,HCV persistent infection can cause malignant lymphoma.The biological significance of lymphotropic HCV has not yet become clear.However,several candidates have been considered for a long time.One is that lymphotropic HCV is an HCV reservoir that might contribute to the recurrence of HCV infection and difficultto-treat disease status.The other important issue is the carcinogenesis of the lymphoid cells and disturbances of the immune responses.Therefore,the extrahepatic diseases might be induced by direct interaction between HCV and lymphoid cells.In this article,we summarize various studies showing the direct effect of HCV on lymphoid cells and discuss the biological significance of lymphotropic HCV.展开更多
To study the kinetics in vivo of a Hantaan virus DNA vaccine, we constructed a fusion DNA vaccine, pEGFP/S, by cloning the S segment of Hantavirus into the vector, pEGFP-C1, which encodes Green fluorescent protein EGF...To study the kinetics in vivo of a Hantaan virus DNA vaccine, we constructed a fusion DNA vaccine, pEGFP/S, by cloning the S segment of Hantavirus into the vector, pEGFP-C1, which encodes Green fluorescent protein EGFP. In this report, we provide evidence that pEGFP/S was distributed and persistently expressed for more than 60 days in several organs after inoculation. Our findings suggest that the persistent immune responses induced by a Hantaan virus DNA vaccine are likely due to the plasmid pEGFP/S deposited in vivo, which acts as a booster immunization.展开更多
Objective:To characterize viral co-infections among representative hospitalized measles cases during the 2014 Hanoi outbreak.Methods:Throat swabs were collected from 54 pediatric patients with confirmed measles,and mo...Objective:To characterize viral co-infections among representative hospitalized measles cases during the 2014 Hanoi outbreak.Methods:Throat swabs were collected from 54 pediatric patients with confirmed measles,and molecular diagnostics performed for 10 additional viral respiratory pathogens(Influenza A/H1N1pdm09;A/H3N2 and influenza B;Parainfluenza 1,2,3;Respiratory Synctial Virus,RSV;human Metapneumovirus,hM PV;Adenovirus and Picornavirus).Results:Twenty-one cases(38.9%) showed evidence of infection with other respiratory viruses:15 samples contained measles plus one additional virus,and 6 samples contained measles plus 2 additional viruses.Adenovirus was detected as a predominant cause of co-infections(13 cases;24.1%),followed by RSV(6 cases;11.1%),A/H1N1pdm09(3 cases;5.6%),PIV3(3 cases;3.7%),Rhinovirus(3 cases;3.7%) and hM PV(1 case;1.96%).Conclusions:Viral co-infections identified from pediatric measles cases may have contributed to increased disease severity and high rate of fatal outcomes.Optimal treatment of measles cases may require control of multiple viral respiratory pathogens.展开更多
Hepatitis B virus(HBV) infection is still a serious worldwide problem, and vaccination is the most effective strategy for primary prevention of the infection. Although universal vaccination may be required for total e...Hepatitis B virus(HBV) infection is still a serious worldwide problem, and vaccination is the most effective strategy for primary prevention of the infection. Although universal vaccination may be required for total eradication, several countries, including Japan, have not yet adopted universal vaccination programs. Some individuals are non-responders to HBV vaccine and several mechanisms responsible for their poor response have been proposed. To overcome non-response, third generation vaccines with pre-S proteins have been developed. These vaccines have shown better antiHBs responses and may also be effective in preventing infection by HBV with S mutant. Improvement of vaccine efficacy by intradermal administration, or coadministration with cytokines or adjuvants, may also be effective in non-responders. The necessity, timing and method of booster vaccination in responders with decreased anti-HBs responses, and effective vaccination against S-mutant HBV, are issues requiring resolution in the global prevention of HBV infection.展开更多
Prevention of hepatitis B virus(HBV) infection with its consequent development of HBV chronic liver disease and hepatocellular carcinoma is a global mandatory goal. Fortunately, safe and effective HBV vaccines are cur...Prevention of hepatitis B virus(HBV) infection with its consequent development of HBV chronic liver disease and hepatocellular carcinoma is a global mandatory goal. Fortunately, safe and effective HBV vaccines are currently available. Universal hepatitis B surface antigen HBV vaccination coverage is almost done. Growing knowledge based upon monitoring and surveillance ofHBV vaccination programs has accumulated and the policy of booster vaccination has been evaluated. This review article provides an overview of the natural history of HBV infection, immune responses and the future of HBV infection. It also summarizes the updated sources, types and uses of HBV vaccines, whether in the preclinical phase or in the post-field vaccination.展开更多
病毒在食源性疾病的爆发中起着至关重要的作用,其中,甲型肝炎病毒(hepatitis A virus,HAV)感染后能够致人衰弱,并引发急性肝衰竭。由于其传染迅速,影响范围广,HAV污染已经给消费者带来了严重的健康风险,且在全球范围内造成了大规模的食...病毒在食源性疾病的爆发中起着至关重要的作用,其中,甲型肝炎病毒(hepatitis A virus,HAV)感染后能够致人衰弱,并引发急性肝衰竭。由于其传染迅速,影响范围广,HAV污染已经给消费者带来了严重的健康风险,且在全球范围内造成了大规模的食源性疫情和经济损失。因此,早期快速准确的检测HAV对于食品安全和疫情暴发的溯源至关重要,以便及时确定并召回受污染的食品,防止感染的进一步发生。传统的HAV检测方法由于检出率不高以及病毒在细胞内的培养周期长等问题,往往耗时费力,无法快速有效地对其进行检测。本文对目前报道较多的HAV快速检测技术进行了阐述和梳理,对各项技术的检出限、检测时间以及优缺点进行了比较,并对HAV快速检测技术研究进行了展望,为后续HAV的快速检测研究提供依据,也有助于进一步探讨与开发HAV快速检测的新技术,以有效防止HAV的传播与危害。展开更多
文摘Hepatitis B virus(HBV)reactivation is a clinically significant challenge in disease management.This review explores the immunological mechanisms underlying HBV reactivation,emphasizing disease progression and management.It delves into host immune responses and reactivation’s delicate balance,spanning innate and adaptive immunity.Viral factors’disruption of this balance,as are interac-tions between viral antigens,immune cells,cytokine networks,and immune checkpoint pathways,are examined.Notably,the roles of T cells,natural killer cells,and antigen-presenting cells are discussed,highlighting their influence on disease progression.HBV reactivation’s impact on disease severity,hepatic flares,liver fibrosis progression,and hepatocellular carcinoma is detailed.Management strategies,including anti-viral and immunomodulatory approaches,are critically analyzed.The role of prophylactic anti-viral therapy during immunosuppressive treatments is explored alongside novel immunotherapeutic interventions to restore immune control and prevent reactivation.In conclusion,this compre-hensive review furnishes a holistic view of the immunological mechanisms that propel HBV reactivation.With a dedicated focus on understanding its implic-ations for disease progression and the prospects of efficient management stra-tegies,this article contributes significantly to the knowledge base.The more profound insights into the intricate interactions between viral elements and the immune system will inform evidence-based approaches,ultimately enhancing disease management and elevating patient outcomes.The dynamic landscape of management strategies is critically scrutinized,spanning anti-viral and immunomodulatory approaches.The role of prophylactic anti-viral therapy in preventing reactivation during immunosuppressive treatments and the potential of innovative immunotherapeutic interventions to restore immune control and proactively deter reactivation.
基金grants from Deutsche Forschungsgemeinschaft, Wilhelm Sander-Stiftung, and Forschungsfrderung Ruhr-Universitt Bochum Medizinische Fakultt to OW
文摘AIM: To evaluate whether intratumoral expression of measles virus fusogenic membrane glycoproteins H and F (MV-FMG), encoded by an adenovirus vector Ad.MV-HI F, alone or in combination with local coexpression of cytokines (IL-2, IL-12, IL-18, IL-21 or GM-CSF), can serve as a platform for inducing tumor-specific immune responses in colon cancer.METHODS: We used confocal laser scanning microscopy and flow cytometry to analyze cell-cell fusion after expression of MV-FMG by dye colocalization. In a syngeneic bilateral subcutaneous MC38 and Colon26 colon cancer model in C57BL/6 and BALB/c mice, we assessed the effect on both the directly vector-treated tumor as well as the contralateral, not directly vector- treated tumor. We assessed the induction of a tumorspecific cytotoxic T lymphocyte (CTL) response with a lactate dehydrogenase (LDH) release assay.RESULTS: We demonstrated in vitro that transduction of MC38 and Colon26 cells with Ad.MV-H/F resulted in dye colocalization, indicative of cell-cell fusion, in addition, in the syngeneic bilateral tumor model we demonstrated a significant regression of the directly vector-inoculated tumor upon intratumoral expression of MV-FMG alone or in combination with the tested cytokines. We observed the highest anti-neoplastic efficacy with MV-FMG and lL-21 coexpression. The degree of tumor regression of the not directly vector-treated tumor correlated with the anti-neoplastic response of the directly vector-treated tumor. This regression was mediated by a tumor-specific CTL response.CONCLUSION: Our data indicate that intratumoral expression of measles virus fusogenic membrane glycoproteins is a promising tool both for direct tumor treatment as well as for tumor vaccination approaches that can be further enhanced by cytokine coexpression.
文摘Hemagglutinin gene of Measles virus(Nepal strain) was amplified by RT PCR technique, cloned and sequenced by the dideoxy mediated chain termination method. The comparison to the standard strain(Edmonston strain) showed many important mutations. The homology of these two strains was 98.17%. Then H gene was cloned into expression vector pCD SRα296 and introduced into COS 7 cells by electroporation method. The expression and function of cloned H gene was checked by hemadsorption assays.
基金Public Benefit Grant of Ministry of Health P.R China (200802035)Basic Research Foundation(General Program) of Yunnan Province (2008CD153)
文摘The complete nucleotide sequence of the measles virus strain IMB-1,which was isolated in China,was determined.As in other measles viruses,its genome is 15,894 nucleotides in length and encodes six proteins.The full-length nucleotide sequence of the IMB-1 isolate differed from vaccine strains (including wild-type Edmonston strain) by 4%-5% at the nucleotide sequence level.This isolate has amino acid variations over the full genome,including in the hemagglutinin and fusion genes.This report is the first to describe the full-length genome of a genotype H1 strain and provide an overview of the diversity of genetic characteristics of a circulating measles virus.
文摘[Objective] The aim of this study was to realize efficient expression of the porcine reproductive and respiratory syndrome virus (PRRSV) ORF7 gene in genetic engineering bacteria and analYze the immunological activity of the recombinant protein after purification. [ Method] The constructed recombinant expression vector pET-ORF7 was transformed into Escherichia co1BL21 (DE3) and induced by IPTG under the optimal condition. After analysis of SDS-PAGE and Western Blot, the expression products were purified by Ni-NTA His · Bind Resin chrom- atographic column under denaturing condition and renatured by gradient dialysis. Subsequently, the immunological activity of the renatured recombinant protein was detected by Westem Blot and indirect ELISA. [ Result] The recombinant plasmid pET-ORF7 expressed in E. coli successfully, and the fusion protein was in the form of inclusion body. By SDS-PAGE detection, the molecular weight of the expression protein was approximate 33 kD, according with the expectation. Analysis by Bandscan software showed that the expressed fusion protein was about 50% of total bacterial protein of BL21 (DE3). Wastem Blot and indirect ELISA detection showed that the renatured protein could react with PRRSV positive serum specifically, indicating its good immunological activity. [ Conclusion] This study lays a foundation for the preparation of PRRSV monoclonal antibody and diagnostic kit.
文摘Hepatitis C virus (HCV) has been recognized to be both a hepato- and lymphotropic virus. HCV lymphotropism represents an essential lap in the pathogenesis of virus-related autoimmune and lymphoproliferative disorders, ranging from clonal expansion of B-cells with organ-and non-organ-specific autoantibody production up to overt non-Hodgkin's lymphoma along a continuous step-by-step model of B-cell lymphomagenesis, where the intermediated mixed cryoglobulinemia could be considered as a stage of suppressible antigen-driven lymphoproliferation. HCV infection of lymphoid ceils could set up privileged reservoirs able to interfere with the host viral clearance efficiency and may be implicated in viral recurrence after apparently successful antiviral therapy. The HCV long-lasting extrahepatic replicative state generates an abnormal systemic immunological response, easily detectable by searching simple laboratory and clinical parameters, mainly represented by vasculitis-like skin features and hypocomplementemia.The presence or absence of this hypersensitivity pattern seems to correlate with the antiviral response and could be identified as a novel immunological cofactor. Further research is required to fully verify the real impact on therapeutic choice/regimen.
文摘BACKGROUND Hepatitis B virus(HBV)infection is a major factor responsible for HBV+hepatocellular carcinoma(HCC).AIM An immunological classification of HBV+HCC may provide both biological insights and clinical implications for this disease.METHODS Based on the enrichment of 23 immune signatures,we identified two immunespecific subtypes(Imm-H and Imm-L)of HBV+HCC by unsupervised clustering.We showed that this subtyping method was reproducible and predictable by analyzing three different datasets.RESULTS Compared to Imm-L,Imm-H displayed stronger immunity,more stromal components,lower tumor purity,lower stemness and intratumor heterogeneity,lower-level copy number alterations,higher global methylation level,and better overall and disease-free survival prognosis.Besides immune-related pathways,stromal pathways(ECM receptor interaction,focal adhesion,and regulation of actin cytoskeleton)and neuro-related pathways(neuroactive ligand-receptor interaction,and prion diseases)were more highly enriched in Imm-H than in Imm-L.We identified nine proteins differentially expressed between Imm-H and Imm-L,of which MYH11,PDCD4,Dvl3,and Syk were upregulated in Imm-H,while PCNA,Acetyl-a-Tubulin-Lys40,ER-α_pS118,Cyclin E2,andβ-Catenin were upregulated in Imm-L.CONCLUSION Our data suggest that“hot”tumors have a better prognosis than“cold”tumors in HBV+HCC and that“hot”tumors respond better to immunotherapy.
文摘The experiment was conducted to inoculate one-day old chicks with March's disease (MD) trivalent and herpesvirus of turkey (HVT) vaccines separately, and then to challenge them with virulent MD virus (vMDV) at the age of 15 days. and 5, 25, 45 and 75 days after the challenge with vMDV, comparing with the control-challenged chicks without immunization, to detect the immunoprotetive efficacy and dynamic changes of the inductive activity of interleukin-2(IL-2), expression of IL-2 receptor and proliferative function of T cells in thymus and spleen; the number of ANAE+T, AP+T cells and IgG, IgM, IgA antibody-producing cells in Bursa Fabricius, spleen,thymus, cecal tonsil and Harder gland; as the amount of T cells and IgG, IgM, IgA in peripheral blood as well as the content of IgG, IgM and IgA in the tear, trachea washings, bile and intestinal fluids of the experimental chicks. The experimental results firstly demonstrate that the immunorcgulation of IL-2, and IL-2 receptor, the cellualr and humoral immune responses were significantly enhanced in the central and peripheral immune organs; the local mucosal immune function were markedly amplified in the respiratory and digestive tracts of the immunized-challenged,chicks, which were closely correlated with the immunoprotection against MD; the immune response and immunoprotective effect of the trivalent vaccine-immunized chicks were much better than those of HVT vaccine-immunized chicks:
基金supported by USPHS grant (No. AI053108) to DanielJ.J. CarrP20 (No. RR017703)+1 种基金an unrestricted grant from Research to Prevent Blindnesssupported by NIAID training grant(No. AI007633)
文摘Type I interferons are critical antiviral cytokines produced following herpes simplex virus type-1 (HSV-1) infection that act to inhibit viral spread. In the present study, we identify HSV-infected and adjacent uninfected corneal epithelial cells as the source of interferon-a. We also report mice deficient in the A1 chain of the type I IFN receptor (CDl18-/) are extremely sensitive to ocular infection with low doses (100 PFU) of HSV-1 as seen by significantly elevated viral titers in the cornea Compared to wild type (WT) controls. The enhanced susceptibil- ity correlated with a loss of CD4+ and CD8+ T cell recruitment and aberrant chemokine production in the cornea despite mounting an adaptive immune response in the draining mandibular lymph node of CDll8/ mice. Taken together, these results highlight the importance of IFN production in both the innate immune response as well as eliciting chemokine production required to facilitate adaptive immune cell trafficking.
基金Supported by A Grant-in-Aid from the Ministry of Education,Culture,Sport,Science,and Technology of Japan,No.25460970,to Kondo Y
文摘It has been reported that the direct binding of hepatitis C virus(HCV)and/or the replication of HCV in the extrahepatic organs and,especially,lymphoid cells,might affect the pathogenesis of extrahepatic diseases with HCV infection.More than one decade ago,several reports described the existence of HCV-RNA in peripheral blood mononuclear cells.Moreover,many reports describing the existence of HCV in B lymphocytes and B cell lymphoma have been published.In addition to B lymphocytes,it was reported that HCV replication could be detected in T lymphocytes and T cell lines.Among the extrahepatic diseases with HCV infection,mixed cryoglobulinemia-related diseases and autoimmunerelated diseases are important for understanding the immunopathogensis of HCV persistent infection.Moreover,HCV persistent infection can cause malignant lymphoma.The biological significance of lymphotropic HCV has not yet become clear.However,several candidates have been considered for a long time.One is that lymphotropic HCV is an HCV reservoir that might contribute to the recurrence of HCV infection and difficultto-treat disease status.The other important issue is the carcinogenesis of the lymphoid cells and disturbances of the immune responses.Therefore,the extrahepatic diseases might be induced by direct interaction between HCV and lymphoid cells.In this article,we summarize various studies showing the direct effect of HCV on lymphoid cells and discuss the biological significance of lymphotropic HCV.
文摘To study the kinetics in vivo of a Hantaan virus DNA vaccine, we constructed a fusion DNA vaccine, pEGFP/S, by cloning the S segment of Hantavirus into the vector, pEGFP-C1, which encodes Green fluorescent protein EGFP. In this report, we provide evidence that pEGFP/S was distributed and persistently expressed for more than 60 days in several organs after inoculation. Our findings suggest that the persistent immune responses induced by a Hantaan virus DNA vaccine are likely due to the plasmid pEGFP/S deposited in vivo, which acts as a booster immunization.
基金funded by the Vietnam National Foundation for Science and Technology Development under grant number-106YS.04-2013.03
文摘Objective:To characterize viral co-infections among representative hospitalized measles cases during the 2014 Hanoi outbreak.Methods:Throat swabs were collected from 54 pediatric patients with confirmed measles,and molecular diagnostics performed for 10 additional viral respiratory pathogens(Influenza A/H1N1pdm09;A/H3N2 and influenza B;Parainfluenza 1,2,3;Respiratory Synctial Virus,RSV;human Metapneumovirus,hM PV;Adenovirus and Picornavirus).Results:Twenty-one cases(38.9%) showed evidence of infection with other respiratory viruses:15 samples contained measles plus one additional virus,and 6 samples contained measles plus 2 additional viruses.Adenovirus was detected as a predominant cause of co-infections(13 cases;24.1%),followed by RSV(6 cases;11.1%),A/H1N1pdm09(3 cases;5.6%),PIV3(3 cases;3.7%),Rhinovirus(3 cases;3.7%) and hM PV(1 case;1.96%).Conclusions:Viral co-infections identified from pediatric measles cases may have contributed to increased disease severity and high rate of fatal outcomes.Optimal treatment of measles cases may require control of multiple viral respiratory pathogens.
文摘Hepatitis B virus(HBV) infection is still a serious worldwide problem, and vaccination is the most effective strategy for primary prevention of the infection. Although universal vaccination may be required for total eradication, several countries, including Japan, have not yet adopted universal vaccination programs. Some individuals are non-responders to HBV vaccine and several mechanisms responsible for their poor response have been proposed. To overcome non-response, third generation vaccines with pre-S proteins have been developed. These vaccines have shown better antiHBs responses and may also be effective in preventing infection by HBV with S mutant. Improvement of vaccine efficacy by intradermal administration, or coadministration with cytokines or adjuvants, may also be effective in non-responders. The necessity, timing and method of booster vaccination in responders with decreased anti-HBs responses, and effective vaccination against S-mutant HBV, are issues requiring resolution in the global prevention of HBV infection.
文摘Prevention of hepatitis B virus(HBV) infection with its consequent development of HBV chronic liver disease and hepatocellular carcinoma is a global mandatory goal. Fortunately, safe and effective HBV vaccines are currently available. Universal hepatitis B surface antigen HBV vaccination coverage is almost done. Growing knowledge based upon monitoring and surveillance ofHBV vaccination programs has accumulated and the policy of booster vaccination has been evaluated. This review article provides an overview of the natural history of HBV infection, immune responses and the future of HBV infection. It also summarizes the updated sources, types and uses of HBV vaccines, whether in the preclinical phase or in the post-field vaccination.
文摘病毒在食源性疾病的爆发中起着至关重要的作用,其中,甲型肝炎病毒(hepatitis A virus,HAV)感染后能够致人衰弱,并引发急性肝衰竭。由于其传染迅速,影响范围广,HAV污染已经给消费者带来了严重的健康风险,且在全球范围内造成了大规模的食源性疫情和经济损失。因此,早期快速准确的检测HAV对于食品安全和疫情暴发的溯源至关重要,以便及时确定并召回受污染的食品,防止感染的进一步发生。传统的HAV检测方法由于检出率不高以及病毒在细胞内的培养周期长等问题,往往耗时费力,无法快速有效地对其进行检测。本文对目前报道较多的HAV快速检测技术进行了阐述和梳理,对各项技术的检出限、检测时间以及优缺点进行了比较,并对HAV快速检测技术研究进行了展望,为后续HAV的快速检测研究提供依据,也有助于进一步探讨与开发HAV快速检测的新技术,以有效防止HAV的传播与危害。