Macon D Coleman, Soon-Duck Ha, S M Mansour Haeryfar, Stephen Dominic Barr, Sung Ouk Kim
{"title":"Cathepsin B plays a key role in optimal production of the influenza A virus.","authors":"Macon D Coleman, Soon-Duck Ha, S M Mansour Haeryfar, Stephen Dominic Barr, Sung Ouk Kim","doi":"10.4172/2324-8955.1000178","DOIUrl":"10.4172/2324-8955.1000178","url":null,"abstract":"<p><strong>Background: </strong>Influenza A virus (IAV) is the etiologic agent of the febrile respiratory illness, commonly referred to as 'flu'. The lysosomal protease cathepsin B (CTSB) has shown to be involved in the lifecycle of various viruses. Here, we examined the role of CTSB in the IAV lifecycle.</p><p><strong>Methods: </strong>CTSB-deficient (CTSB<sup>-/-</sup>) macrophages and the human lung epithelial cell line A549 cells treated with CA-074Me were infected with the A/Puerto Rico/8/34 strain of IAV (IAV-PR8). Viral entry and propagation were measured through quantitative real-time RT-PCR; production and localization of hemagglutinin (HA) protein in the infected host cells were analysed by Western blots, flow cytometry and confocal microscopy; production of progeny viruses were measured by a hemagglutination assay.</p><p><strong>Results: </strong>CTSB<sup>-/-</sup> macrophages and CA-074Me-treated A549 cells had no defects in incorporating IAV-PR8 virions and permitting viral RNA synthesis. However, these cells produced significantly lower amounts of HA protein and progeny virions than wild-type or untreated cells.</p><p><strong>Conclusion: </strong>These data indicate that CTSB is involved in the expression of IAV-PR8 HA protein and subsequent optimal production of IAV-PR8 progeny virions. Targeting CTSB can be a novel therapeutic strategy for treating IAV infection.</p>","PeriodicalId":90004,"journal":{"name":"Journal of virology & antiviral research","volume":"7 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5770218/pdf/nihms6993.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35750444","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Krystal Colón, Fabián Vázquez-Santiago, Vanessa Rivera-Amill, Gisela Delgado, Steven E Massey, Valerie Wojna, Richard J Noel, Loyda M Meléndez
{"title":"HIV gp120 sequence variability associated with HAND in Hispanic Women.","authors":"Krystal Colón, Fabián Vázquez-Santiago, Vanessa Rivera-Amill, Gisela Delgado, Steven E Massey, Valerie Wojna, Richard J Noel, Loyda M Meléndez","doi":"10.4172/2324-8955.1000143","DOIUrl":"https://doi.org/10.4172/2324-8955.1000143","url":null,"abstract":"<p><strong>Objective: </strong>HIV-1 variants with different tropisms are associated with various neuropathologies. This study intends to determine if this correlation is determined by unique viral <i>env</i> sequences. We hypothesize that HIV-1 envelope gene sequence changes are associated with cognition status.</p><p><strong>Methods: </strong>Viral RNA was extracted from peripheral blood mononuclear cells (PBMCs) co-cultures derived from HIV-1 infected Hispanic women that had been characterized for HIV associated neurocognitive disorders (HAND).</p><p><strong>Results: </strong>Analyses of the C2V4 region of HIV gp120 demonstrated that increased sequence diversity correlates with cognition status as sequences derived from subjects with normal cognition exhibited less diversity than sequences derived from subjects with cognitive impairment. In addition, differences in V3 and V4 loop charges were also noted as well as differences in the N-glycosylation of the V4 region.</p><p><strong>Conclusions: </strong>Our data suggest that the genetic signature within the C2V4 region may contribute to the pathogenesis of HAND. HIV <i>env</i> sequence characteristics for the isolates grouped in milder forms of HAND can provide insightful information of prognostic value to assess neurocognitive status in HIV<sup>+</sup> subjects, particularly during the era of highly prevalent milder forms of HAND.</p>","PeriodicalId":90004,"journal":{"name":"Journal of virology & antiviral research","volume":"4 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2015-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4922650/pdf/nihms789866.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34525918","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Fabián Vázquez-Santiago, Yashira García, Ivelisse Rivera-Román, Richard J Noel, Valerie Wojna, Loyda M Meléndez, Vanessa Rivera-Amill
{"title":"Longitudinal Analysis of Cerebrospinal Fluid and Plasma HIV-1 Envelope Sequences Isolated From a Single Donor with HIV Asymptomatic Neurocognitive Impairment.","authors":"Fabián Vázquez-Santiago, Yashira García, Ivelisse Rivera-Román, Richard J Noel, Valerie Wojna, Loyda M Meléndez, Vanessa Rivera-Amill","doi":"10.4172/2324-8955.1000135","DOIUrl":"10.4172/2324-8955.1000135","url":null,"abstract":"<p><strong>Objective: </strong>Combined antiretroviral treatment (cART) has changed the clinical presentation of HIV-associated neurocognitive disorders (HAND) to that of the milder forms of the disease. Asymptomatic neurocognitive impairment (ANI) is now more prevalent and is associated with increased morbidity and mortality risk in HIV-1-infected people. HIV-1 envelope (<i>env</i>) genetic heterogeneity has been detected within the central nervous system (CNS) of individuals with ANI. Changes within <i>env</i> determine co-receptor use, cellular tropism, and neuropathogenesis. We hypothesize that compartmental changes are associated with HIV-1 <i>env</i> C2V4 during ANI and sought to analyze paired HIV-1 <i>env</i> sequences from plasma and cerebrospinal fluid (CSF) of a female subject undergoing long-term cART.</p><p><strong>Methods: </strong>Paired plasma and CSF samples were collected at 12-month intervals and HIV-1 <i>env</i> C2V4 was cloned and sequenced.</p><p><strong>Results: </strong>Phylogenetic analysis of paired samples consistently showed genetic variants unique to the CSF. Phenotypic prediction showed CCR5 (R5) variants for all CSF-derived sequences and showed minor X4 variants (or dual-tropic) in the plasma at later time points. Viral compartmentalization was evident throughout the study, suggesting that the occurrence of distinctive <i>env</i> strains may contribute to the neuropathogenesis of HAND.</p><p><strong>Conclusions: </strong>Our study provides new insights about the genetic characteristics within the C2V4 of HIV-1 <i>env</i> that persist after long-term cART and during the course of persistent ANI.</p>","PeriodicalId":90004,"journal":{"name":"Journal of virology & antiviral research","volume":"4 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2015-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4498488/pdf/nihms692834.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34002506","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
J. Gutierrez, Krysten A Jones, Roxana Flores, A. Singhania, C. Woelk, R. Schooley, D. Wyles
{"title":"Vitamin D Metabolites Inhibit Hepatitis C Virus and Modulate Cellular Gene Expression.","authors":"J. Gutierrez, Krysten A Jones, Roxana Flores, A. Singhania, C. Woelk, R. Schooley, D. Wyles","doi":"10.4172/2324-8955.1000129","DOIUrl":"https://doi.org/10.4172/2324-8955.1000129","url":null,"abstract":"BACKGROUND AND AIMS\u0000Previous studies suggest that low serum 25-hydroxyvitamin D [25(OH) D] levels are associated with reduced responsiveness to interferon and ribavirin therapy. We investigated the impact of vitamin D metabolites on HCV and cellular gene expression in cultured hepatoma cells.\u0000\u0000\u0000METHODS\u0000HCV Replicon cell lines stably expressing luciferase reporter constructs (genotype 1b and 2a replicon) or JC1-Luc2a were incubated in the presence of vitamin D2, vitamin D3 or 1,25-dihydroxyvitamin D3 (1,25(OH)2D3). Presence of HCV was quantified by a luciferase reporter assay and immunoblot of the Core protein. Synergy of interferon-alpha A/D (IFN-α) and 1,25(OH)2D3 was evaluated using the Chou-Talalay method. Cellular gene expression by microarray analysis using Illumina Bead Chips and real-time quantitative PCR.\u0000\u0000\u0000RESULTS\u0000Vitamin D2, D3 and 1,25(OH)2D3 each demonstrated anti-HCV activity at low micro molar concentrations. In vitro conversion from D3 to 25(OH)D3 was shown by LC/MS/MS. Combination indices of 1,25(OH)2D3 and IFN-α demonstrated a synergistic effect (0.23-0.46) and significantly reduced core expression by immunoblot. Differentially expressed genes were identified between Huh7.5.1 cells in the presence and absence of 1,25(OH)2D3 and HCV. Genes involved with classical effects of vitamin D metabolism and excretion were activated, along with genes linked to autophagy such as G-protein coupled receptor 37 (GPR37) and Hypoxia-inducible factor 1-alpha (HIF1a). Additionally, additive effects of 1,25(OH)2D3 and IFN-α were seen on mRNA expression of chemokine motif ligand 20 (CCL20).\u0000\u0000\u0000CONCLUSIONS\u0000This study shows that vitamin D reduces HCV protein production in cell culture synergistically with IFN-α. Vitamin D also activates gene expression independently and additively with IFN-α and this may explain its ability to aid in the clearance of HCV in vivo.","PeriodicalId":90004,"journal":{"name":"Journal of virology & antiviral research","volume":"3 3 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2014-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70248123","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Role of Coatomer Protein I in Virus Replication.","authors":"Jennifer A Thompson, Jay C Brown","doi":"10.4172/2324-8955.1000102","DOIUrl":"https://doi.org/10.4172/2324-8955.1000102","url":null,"abstract":"<p><p>Coatomer protein I (COPI) is well known as the protein coat surrounding vesicles involved in returning endoplasmic reticulum (ER)-resident proteins to the ER. COPI coats are also found in vesicles involved in other trafficking processes including endocytosis, autophagy and anterograde transport in the secretory pathway. In view of the diverse functions of COPI proteins, it is expected that they will affect virus replication, and many reports of such COPI involvement have now appeared. The experimental approaches most often employ specific siRNA to deplete COPI subunits or brefeldin A to block COPI activation. Here we briefly describe the results obtained with viruses in which COPI is found to have a role in replication. The results demonstrate that COPI affects viruses quite differently with effects observed in processes such as entry, RNA replication, and intracellular transport of viral proteins.</p>","PeriodicalId":90004,"journal":{"name":"Journal of virology & antiviral research","volume":"1 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2012-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3879076/pdf/nihms500784.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32003720","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}