Acta virologica最新文献

Broad human immunodeficiency virus type 1 (HIV-1) Gag-specific cellular responses can control viremia and provide slow progression to Acquired immunodeficiency syndrome (AIDS). In this study, we evaluate multiple HIV-1 Gag-specific lymphoproliferative responses and find their connection with cluster of differentiation 4 (CD4)+ T cell count and viral load from chronically HIV-1-infected patients. We further search for the correlation between multiple Gag-specific lymphoproliferative responses and changes in highly active antiretroviral therapy (HAART) regimen. We found correlation between Gag-specific responses and higher CD4+ T cells nadir and low HIV-1 viral load. Additionally, we observed that HIV-1-infected subjects did not need to change HAART regimen, when multiple Gag responses are present. We concluded that the start of HAART when CD4+ T cell nadir is the highest as possible may promote Gag-specific cellular responses conservation. Multiple Gag responses must be important to suppress HIV-1 replication. Preserved Gag-specific responses reduce HIV-1 viral load and are associated with stability of HAART regimen. Keywords: HIV-1; Gag; lymphoproliferation; viral load; HAART.

Nora virus is a RNA picorna-like virus that produces a persistent infection in Drosophila melanogaster. The genome is approximately 12,300 bases and is divided into four open reading frames (ORFs). Structurally, there are four important viral proteins: VP3, VP4A, VP4B, and VP4C. Three proteins (VP4A, VP4B, and VP4C) that form the virion's capsid are encoded by ORF 4, which produces a polyprotein that is post-translationally cleaved. The fourth protein (VP3) is encoded by ORF 3 and it is hypothesized to play a role in virion stability. The genes for these proteins were individually cloned into Escherichia coli, expressed, and the proteins were purified. Virus-like particles (VLPs) were assembled in vitro by mixing the proteins together in different combinations and measured via electron microscopy. Assemblies that contained VP4A and/or VP3 created VLPs with similar sizes to purified empty Nora virus capsids, potentially indicating that VP4A and/or VP3 are vital for Nora virus capsid structure, assembly, and/or stability. Not only does this study provide insight into the role of Nora virus proteins, but it may also lead to a deeper understanding of how Nora virus or other picorna-like viruses undergo assembly.  Keywords: RNA viruses; Nora virus; picorna-like virus; virus-like particles; capsid assembly.

Proteomics is widely used to investigate and understand viral infections in livestock and poultry. The effects of infections on abundance, post-translational modifications, and interactions of host cell proteins have been systematically studied using proteomic methods, such as two-dimensional electrophoresis and mass spectrometry. Such research increases our understanding of the pathogenesis of viral infections and contributes to the development of novel anti-viral drugs for the livestock and poultry industries. Keywords: proteomics; infectious diseases; poultry and livestock; application.

The effects of double combinations of enterovirus (EV) replication inhibitors against Coxsackieviruses B1 (neurotropic Connecticut-5 strain) and B3 (cardiotropic Woodruff and neurotropic Nancy strains) were tested in cell culture experiments. Compounds with different mechanisms of action were studied: pleconaril, guanidine.HCl, MDL-860 and oxoglaucine. A three-dimensional method was applied for determining the character of the combined effect. The study determined several synergistic double combinations: guanidine.HCL + pleconaril or MDL-860 against Coxsackievirus B1; MDL-860 + each of the other EV replication inhibitors and guanidine.HCl + pleconaril against the cardiotropic Woodruff strain of Coxsackievirus B3; MDL-860 + oxoglaucine against the neurotropic Nancy strain of Coxsackievirus B3. No increased cytotoxicity was manifested in any of the tested double combinations. Keywords: antivirals; combination activity; Coxsackieviruses.

Daphnia pulex from a small pond were infected by an iridescence virus. Infected daphnia differed from healthy ones due to the intense characteristic pink reflected iridescent color. Infected individuals collected in the field died in laboratory as a result of the iridoviral infection. Ultrastructural analysis using electron microscopy revealed highly abundant icosahedral virions in the cytoplasm of multiple types of tissue in the infected daphnids. The mean particle sizes were approximately 200 nm (n = 150) edge-to-edge and 185 nm point-to-point. Keywords: daphnia; Daphnia pulex; iridovirus; electron microscopy.

Marek's disease (MD) is a highly contagious neoplastic disease of chickens associated with economic losses, often due to visceral lymphomas. The etiological agent is MD virus serotype 1 (MDV-1), also called Gallid alphaherpesvirus 2 (GaHV-2). Despite intensive vaccination, MDV is constantly evolving and maintaining its presence in the world. The aim of this study was to genetically analyze a highly oncogenic MDV/Tur/2019 strain obtained from a poultry farm in Turkey's Elazig province in 2019. Genes associated with viral pathogenicity and oncogenicity Marek's EcoRI-Q-encoded protein (MEQ), phosphoprotein-38 (pp38), and viral interleukin 8 (vIL-8) were selected for this purpose. The vIL-8 nucleotide sequence showed high similarity (100% identity) to some European (EU-1, Polen 5) and Asian (03 India, GADVASU-M2) MDV strains. The pp38 nucleotide sequence showed high similarity (100% identity) to some American (CU-2, JM/102W, RB1B) and European (MD70/13, ATE2539) MDV strains. There were no disrupted four-proline molecules (PPPP) within the transactivation domain of the MEQ. However, according to phylogenetic results, the MDV/Tur/2019 strain was included in cluster 2a alongside European MDV strains (Polish, Hungarian, Italian) with very virulent and very virulent plus pathotypes. In conclusion, we believe that the MDV/Tur/2019 strain obtained from turkey herpesvirus (HVT)-vaccinated chickens has a very virulent or very virulent plus pathotype. Although this result provides some clues regarding the virulence of this strain, in vivo studies are needed to achieve exact pathotyping. Further, combination of HVT with the CVI988 strain should be used for vaccination to provide the best protection, as highly pathogenic MDV strains can break sterile immunity against the HVT vaccine. Keywords: GaHV-2; Marek's disease; oncogenes; Turkey.

Direct acting antiviral agents (DAAs) are a group of antiviral drugs that inhibit specific non-structural proteins of the virus and disrupt viral replication and infection. DAAs regimens for hepatitis C virus (HCV) infection provide a particular event to tackle mechanistic intracellular relationships between the innate immunity and HCV, potentially providing perceptions about the rate of the viral replication and complex decay. Interleukin 29 (IL-29) prevents the replication of HCV. IFN-inducible protein 10 (IP-10) plays a significant role in the pathogenesis of HCV infection. MIG/CXCL9 are produced by inflammatory and stromal cells such as hepatocytes following either stimulation by interferon lambda (IFNγ) or viral infection. This study aimed to evaluate the co-expression of IL-29, IP-10 and MIG in peripheral blood mononuclear cells (PBMCs) from untreated and treated chronic HCV patients with DAAs. This study included group of twenty naïve HCV patients, group of twenty sustained viral response (SVR) patients and a control group that consisted of 10 healthy subjects. All subjects were tested for liver enzymes, serum albumin level, total serum bilirubin, platelet count, prothrombin activity and viral load. Relative gene expression of IL-29, IP-10, and MIG in PBMCs from all subjects was determined using real time PCR. The mean value of IL-29, IP-10 and MIG gene expression significantly increased in both naïve HCV and SVR groups of patients as compared to normal subjects. The corresponding value was significantly lower in patients with SVR compared to naïve HCV patients. Infection with HCV significantly trigged the co-expression of IL-29, IP-10, and CXCL9 (MIG) genes in PBMCs of chronic hepatitis C patients and significantly down-regulated in those who achieved SVR after successful DAAs therapy. Keywords: IP10; MIG; IL29; HCV; DAAs; gene expression.

The response of the host immune system should be appropriate to fight against pandemic 2009 H1N1 (pH1N1) influenza A virus without causing damage to its self. T cells play an indispensable role in the fight against the virus, but have the potential to cause host immunopathological changes. A better understanding of the immunoregulation that occurs during pH1N1 infection is necessary for preventing severity of the disease. In this study, we found that a significantly higher percentage of Vδ1+ T cells and increased expression of activation markers in total T cells in patients with moderate pH1N1 infection could lead to its efficient fight against the virus. On the other hand, the percentages of total and CD4+ T cells were decreased along with an increased expression of exhaustion marker-Tim-3 on T cells that might suppress excessive T cell responses in the host. This tuning of T cell responses might be necessary in efficient combat against pH1N1 virus, without aggravating T cell mediated immunopathology in patients with moderate pH1N1-infection. Keywords: pH1N1; T cells; activation; exhaustion; Tim-3.

African swine fever (ASF) is an acute and severe infectious disease that seriously endangers the global porcine industry. In order to develop ASF serodiagnostic reagents with high specificity and sensitivity, in the present study, the antigenic epitopes of P72 protein of African swine fever virus (ASFV) were analyzed, and the ASFV multi-epitope fusion gene MeP72 in tandem with the dominant linear epitopes was constructed. The recombinant multi-epitope fusion MeP72 (reMeP72) was prepared in Escherichia coli. A colloidal gold-based immunochromatographic assay (CGIA) based on reMeP72 was developed for the detection of antibodies against ASFV. A total of 139 pig clinical serum samples were used for assessment of the potential diagnostic value of reMeP72. The results showed that CGIA did not cross-react with positive sera of viruses, such as classical swine fever virus (CSFV), porcine circovirus type 2 (PCV2), pseudorabies virus (PRV), porcine reproductive and respiratory syndrome virus (PRRSV) and swine influenza virus (SIV), showing high specificity. Sensitivity analysis showed that CGIA could detect ASFV-positive serum at a dilution of 1:64. Compared with commercial ASFV kits, the sensitivity and specificity of ASFV CGIA based on reMeP72 protein were 85.7% and 97.6%, respectively. The agreement rate of the two methods was 96.4%, showing a good detection performance. The results indicated that the reMeP72 was of potential value for the serodiagnosis of ASF. Keywords: African swine fever virus; P72 gene; antigenic protein; colloidal gold-based immunochromatographic assay.

The current limited understanding of HCV entry mechanisms hinders the development of specific antiviral drug screening techniques and vaccine assessment. HCV subtypes and cellular surface proteins both can affect virus tropism. Human factors such as low-density lipoprotein receptor (hLDLR), CD81 (hCD81), scavenger receptor class B type I (hSR-BI), claudin 1 (hCLDN1), and occludin (hOCLN) assist HCV entry into hepatocytes. Here, we studied the importance of five human proteins in the process of cell culture-derived (HCVcc) and serum-derived (HCV-sd) HCV entry using constructed humanized mouse hepatocytes and mouse models. We determined that unlike hLDLR, hSR-BI was an indispensable factor for 1b genotype HCV adsorption. Furthermore, this attachment can be completely prevented by treatment with a monoclonal antibody targeting hSR-BI. Our data support the idea that SR-BI is an essential factor in HCV infection, particularly during the initial HCV particle-binding step. This novel finding will facilitate the development of antiviral drugs and vaccines. Keywords: hepatitis C virus; virus internalization; model construction; hSR-BI.