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Journal of Virology

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https://www.readbyqxmd.com/read/28077659/hiv-controllers-exhibit-enhanced-frequencies-of-mhc-class-ii-tetramer-gag-specific-cd4-t-cells-in-chronic-clade-c-hiv-1-infection
#1
Faatima Laher, Srinika Ranasinghe, Filippos Porichis, Nikoshia Mewalal, Karyn Pretorius, Nasreen Ismail, Søren Buus, Anette Stryhn, Mary Carrington, Bruce D Walker, Thumbi Ndung'u, Zaza M Ndhlovu
: Immune control of viral infections is heavily dependent on helper CD4(+) T cell function. However, understanding the contribution of HIV-specific CD4(+) T cell responses to immune protection against HIV-1, particularly in clade C infection remains incomplete. Recently, MHC class II tetramers have emerged as a powerful tool for interrogating antigen specific CD4(+) T cells without relying on effector functions. Here, we defined the MHC class II alleles for immunodominant Gag CD4(+) T cell epitopes in clade C virus infection, constructed MHC class II tetramers, and then used these to define the magnitude, function, and relation to viral load of HIV-specific CD4(+) T cell responses in a cohort of untreated HIV clade C infected persons...
January 11, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28077658/a-cytoplasmic-rna-virus-alters-the-function-of-the-cell-splicing-protein-srsf2
#2
Efraín E Rivera-Serrano, Ethan J Fritch, Elizabeth H Scholl, Barbara Sherry
: To replicate efficiently, viruses must create favorable cell conditions and overcome cell antiviral responses. We previously reported that the reovirus protein μ2 from strain T1L, but not strain T3D, represses one antiviral response: interferon-α/β (IFN-β) signaling. We report here that T1L but not T3D μ2 localizes to nuclear speckles where it forms a complex with the mRNA splicing factor SRSF2 and alters its sub-nuclear localization. Reovirus replicates in cytoplasmic viral factories and there is no evidence that reovirus genomic or messenger RNAs are spliced, suggesting that T1L μ2 might target splicing of cell RNAs...
January 11, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28077657/lmp1-and-lmp2a-collaborate-to-promote-epstein-barr-virus-ebv-induced-b-cell-lymphomas-in-a-cord-blood-humanized-mouse-model-but-are-not-essential
#3
Shi-Dong Ma, Ming-Han Tsai, James C Romero-Masters, Erik A Ranheim, Shane M Huebner, Jillian Bristol, Henri-Jacques Delecluse, Shannon C Kenney
: Epstein-Barr virus (EBV) infection is associated with B cell lymphomas in humans. The ability of EBV to convert human B cells into long-lived lymphoblastoid cell lines (LCLs) in vitro requires the collaborative effects of EBNA2 (which hijacks notch signaling), LMP1 (which mimics CD40 signaling), and EBNA 3A/3C (which inhibit oncogene-induced senescence and apoptosis). However, we recently showed that an LMP1-deleted EBV mutant induces B cell lymphomas in a newly developed cord blood-humanized mouse model that allows EBV-infected B cells to interact with CD4 T cells (the major source of CD40 ligand)...
January 11, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28077656/hierarchical-and-redundant-roles-of-activating-fc%C3%AE-rs-in-protection-against-influenza-disease-by-m2e-specific-igg1-and-igg2a-antibodies
#4
Silvie Van den Hoecke, Katrin Ehrhardt, Annasaheb Kolpe, Karim El Bakkouri, Lei Deng, Hendrik Grootaert, Steve Schoonooghe, Anouk Smet, Mostafa Bentahir, Kenny Roose, Michael Schotsaert, Bert Schepens, Nico Callewaert, Falk Nimmerjahn, Peter Staeheli, Hartmut Hengel, Xavier Saelens
: The ectodomain of matrix protein 2 is a universal influenza A vaccine candidate that provides protection through antibody-dependent effector mechanisms. Here we compared the functional engagement of Fcγ Receptor family members by two M2e-specific monoclonal antibodies: mAb 37 (IgG1) and mAb 65 (IgG2a), which recognize a similar epitope in M2e with similar affinity. Binding of mAb 65 to influenza A virus-infected cells triggered all three activating mouse Fcγ receptors in vitro, whereas mAb 37 only activated FcγRIII...
January 11, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28077655/expression-of-ifnlr1-on-intestinal-epithelial-cells-is-critical-to-the-antiviral-effects-of-ifn-lambda-against-norovirus-and-reovirus
#5
Megan T Baldridge, Sanghyun Lee, Judy J Brown, Nicole McAllister, Kelly Urbanek, Terence S Dermody, Timothy J Nice, Herbert W Virgin
: Interferon-lambda (IFN-λ) has potent antiviral effects against multiple enteric viral pathogens, including norovirus and rotavirus, in both preventing and curing infection. Because the intestine includes a diverse array of cell types, however, the cell(s) upon which IFN-λ acts to exert its antiviral effects are unclear. Here, we sought to identify IFN-λ responsive cells by generation of mice with lineage-specific deletion of the receptor for IFN-λ, Ifnlr1 We found that expression of IFNLR1 on intestinal epithelial cells (IECs) in the small intestine and colon is required for enteric IFN-λ antiviral activity...
January 11, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28077654/neutralization-of-diverse-human-cytomegalovirus-strains-conferred-by-antibodies-targets-viral-gh-gl-pul128-131-pentameric-complex
#6
Sha Ha, Fengsheng Li, Matthew C Troutman, Daniel C Freed, Aimin Tang, John W Loughney, Dai Wang, I-Ming Wang, Josef Vlasak, David C Nickle, Richard R Rustandi, Melissa Hamm, Pete A DePhillips, Ningyan Zhang, Jason S McLellan, Hua Zhu, Stuart P Adler, Michael A McVoy, Zhiqiang An, Tong-Ming Fu
: Human cytomegalovirus (HCMV) is the leading cause of congenital viral infection and developing a prophylactic vaccine is of high priority to public health. We recently reported a replication-defective human cytomegalovirus with restored pentameric complex gH/gL/pUL128-131 for prevention of congenital HCMV infection. While the quantity of vaccine-induced antibody responses can be measured in a viral neutralization assay, assessing the quality of such responses, including the ability of vaccine-induced antibodies to cross neutralize the field strains of HCMV, remains a challenge...
January 11, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28077653/characterizing-hiv-1-splicing-using-next-generation-sequencing
#7
Ann Emery, Shuntai Zhou, Elizabeth Pollom, Ronald Swanstrom
: Full-length HIV-1 RNA serves as the genome or as an mRNA, or this RNA undergoes splicing using four donors and ten acceptors to create over 50 physiologically relevant transcripts in two size classes (1.8 kb and 4 kb). We developed an assay using Primer ID-tagged deep sequencing to quantify HIV-1 splicing. Using the NL4-3 lab strain we found that A5 (env/nef) is the most commonly used acceptor (about 50%) with A3 (tat) the least used (about 3%). Two small exons are made when a splice to acceptor A1 or A2 is followed by activation of donor D2 or D3, and the high-level use of D2 and D3 dramatically reduces the amount of vif and vpr transcripts...
January 11, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28077652/exosome-mediated-intercellular-communication-between-hepatitis-c-virus-infected-hepatocytes-and-hepatic-stellate-cells
#8
Pradip B Devhare, Reina Sasaki, Shubham Shrivastava, Adrian M Di Bisceglie, Ranjit Ray, Ratna B Ray
: Fibrogenic pathways in the liver are principally regulated by activation of hepatic stellate cells (HSC). Fibrosis is associated with chronic hepatitis C virus (HCV) infection, although the mechanism is poorly understood. HSC comprise the major population of the non-parenchymal cells in the liver. Since HCV does not replicate in HSC, we hypothesized that exosomes secreted from HCV-infected hepatocytes activate HSC. Primary or immortalized human hepatic stellate cells (LX2) were exposed to exosomes derived from HCV-infected hepatocytes (HCV-exo) and the expression of fibrosis related genes was examined...
January 11, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28077651/bromodomain-containing-4-brd4-couples-nf%C3%AE%C2%BAb-rela-with-airway-inflammation-and-the-irf-rig-i-amplification-loop-in-respiratory-syncytial-virus-infection
#9
Bing Tian, Jun Yang, Yingxin Zhao, Teodora Ivanciuc, Hong Sun, Roberto P Garofalo, Allan R Brasier
: The airway mucosa expresses protective interferon (IFN) and inflammatory cytokines in response to Respiratory Syncytial Virus (RSV) infection. In this study, we examine the role of bromodomain containing 4 (BRD4) in mediating this innate immune response in human small airway epithelial cells. We observe that RSV induces BRD4 to complex with NFκB/RelA. BRD4 is functionally required for expression of the NFκB-dependent inflammatory gene regulatory network (GRN), including the IFN Response Factor (IRFs)-1 and -7 that mediate a cross-talk pathway for RIG-I upregulation...
January 11, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28077650/melanin-or-melanin-like-substance-interacts-with-the-n-terminal-portion-of-prion-protein-and-inhibits-abnormal-prion-protein-formation-in-prion-infected-cells
#10
Taichi Hamanaka, Keiko Nishizawa, Yuji Sakasegawa, Ayumi Oguma, Kenta Teruya, Hiroshi Kurahashi, Hideyuki Hara, Suehiro Sakaguchi, Katsumi Doh-Ura
Prion diseases are progressive fatal neurodegenerative illnesses caused by the accumulation of transmissible abnormal prion protein (PrP). To find treatments for prion diseases, we searched for substances from natural resources that inhibit abnormal PrP formation in prion-infected cells. We found that high-molecular-weight components from insect cuticle extracts reduced abnormal PrP levels. The chemical nature of these components was consistent with that of melanin. In fact, synthetic melanin produced from tyrosine or 3-hydroxy-l-tyrosine inhibited abnormal PrP formation...
January 11, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28077649/tcr-clonotype-specific-differences-in-inhibitory-activity-of-hiv-1-cytotoxic-t-cell-clones-is-not-mediated-by-tcr-alone
#11
Nina C Flerin, Huabiao Chen, Tynisha D Glover, Pedro A Lamothe, Jian Hua Zheng, Justin W Fang, Zaza M Ndhlovu, Evan W Newell, Mark M Davis, Bruce D Walker, Harris Goldstein
: Functional analysis of T cell responses in HIV-infected individuals has indicated that virus-specific CD8(+) T cells with superior antiviral efficacy are well represented in HIV-1 controllers but are rare or absent in HIV-1 progessors. To define the role of individual TCR clonotypes in differential antiviral CD8(+) T cell function, we performed detailed functional and mass cytometric cluster analysis of multiple CD8(+) T cell clones recognizing the identical HLA-B*2705-restricted HIV-1 epitope KK10 (KRWIILGLNK)...
January 11, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28077648/human-papillomavirus-16-e6-up-regulates-apobec3b-via-the-tead-transcription-factor
#12
Seiichiro Mori, Takamasa Takeuchi, Yoshiyuki Ishii, Takashi Yugawa, Tohru Kiyono, Hiroshi Nishina, Iwao Kukimoto
: The cytidine deaminase APOBEC3B (A3B) underlies the genetic heterogeneity of several human cancers including cervical cancer, which is caused by human papillomavirus (HPV) infection. We previously identified a region within the A3B promoter that is activated by the viral protein HPV16 E6 in human keratinocytes. Here, we discovered three sites recognized by the TEAD family of transcription factors within this region of the A3B promoter. Reporter assays in HEK293 cells showed that exogenously expressed TEAD4 induced A3B promoter activation through binding to these sites...
January 11, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28077647/sensitive-next-generation-sequencing-method-reveals-deep-genetic-diversity-of-hiv-1-in-the-democratic-republic-of-the-congo
#13
M A Rodgers, E Wilkerson, A Vallari, C McArthur, L Sthreshley, C A Brennan, G Cloherty, T de Oliveira
: As the epidemiological epicentre of the human immunodeficiency virus (HIV) pandemic, the Democratic Republic of the Congo (DRC) is a reservoir of circulating HIV strains exhibiting high levels of diversity and recombination. In this study, we characterized HIV specimens collected in two rural areas of the DRC between 2001 and 2003 to identify rare strains of HIV. The env gp41 region was sequenced and characterized for 172 HIV-positive specimens. The env sequences were predominantly subtype A (43...
January 11, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28077646/adenovirus-modulates-toll-like-receptor-4-signaling-by-reprogramming-orp1l-vap-protein-contacts-for-cholesterol-transport-from-endosomes-to-the-endoplasmic-reticulum
#14
Nicholas L Cianciola, Stacey Chung, Danny Manor, Cathleen R Carlin
: Human adenoviruses generally cause mild self-limiting infections but can lead to serious disease and even be fatal in high-risk individuals, underscoring the importance of understanding how the virus counteracts host defense mechanisms. This study had two goals. First, determine the molecular basis of cholesterol homeostatic responses induced by the early region 3 membrane protein RIDα via its direct interaction with the sterol-binding protein ORP1L. Second, determine how this interaction regulates innate immunity to adenovirus...
January 11, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28077645/herpes-simplex-virus-1-abrogates-cgas-sting-mediated-cytosolic-dna-sensing-pathway-via-its-virion-host-shutoff-protein-ul41
#15
Chenhe Su, Chunfu Zheng
: Cyclic GMP-AMP synthase (cGAS) is a key DNA sensor capable of detecting microbial DNA and activating the adaptor protein stimulator of interferon genes (STING), leading to interferon (IFN) production and host antiviral responses. Cells exhibited reduced type I IFN production in response to cytosolic DNA in the absence of cGAS. Although cGAS/STING-mediated DNA-sensing signal is crucial for host defense against many viruses, especial for DNA viruses, few viral components have been identified to specifically target this signaling pathway...
January 11, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28077644/ultrasensitive-hiv-1-p24-detects-single-infected-cells-and-differences-in-reservoir-induction-by-latency-reversal-agents
#16
Caroline Pereira Bittencourt Passaes, Timothée Bruel, Jérémie Decalf, Annie David, Mathieu Angin, Valerie Monceaux, Michaela Muller-Trutwin, Nicolas Noel, Katia Bourdic, Olivier Lambotte, Matthew L Albert, Darragh Duffy, Olivier Schwartz, Asier Sáez-Cirión
: The existence of HIV reservoirs in infected individuals under cART represents a major obstacle towards cure. Viral reservoirs are assessed by quantification of HIV nucleic acids, which does not discriminate between infectious and defective viruses, or by viral outgrowth assays, which requires large number of cells and long-term cultures. Here, we used an ultrasensitive p24 digital assay, which we report to be 1000 fold more sensitive than classical ELISA in the quantification of HIV-1 Gag p24 production in HIV-infected individuals samples...
January 11, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28077643/efficient-vpu-mediated-tetherin-antagonism-by-an-hiv-1-group-o-strain
#17
Katharina Mack, Kathrin Starz, Daniel Sauter, Simon Langer, Frederic Bibollet-Ruche, Gerald H Learn, Christina M Stürzel, Marie Leoz, Jean-Christophe Plantier, Matthias Geyer, Beatrice H Hahn, Frank Kirchhoff
: Simian immunodeficiency viruses (SIVs) use their Nef proteins to counteract the restriction factor tetherin. However, a deletion in human tetherin prevents antagonism by the Nef proteins of SIVcpz and SIVgor, which represent the ape precursors of human immunodeficiency virus type 1 (HIV-1). To promote virus release from infected cells, pandemic HIV-1 group M strains evolved Vpu as tetherin antagonist, while the Nef protein of less widespread HIV-1 group O strains acquired the ability to target a region adjacent to this deletion...
January 11, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28077642/studies-on-the-interaction-of-tumor-derived-hd5-alpha-defensins-with-adenoviruses-and-implications-for-oncolytic-adenovirus-therapy
#18
Charles Vragniau, Jens-Martin Hübner, Peter Beidler, Sucheol Gil, Kamola Saydaminova, Zhuo-Zhuang Lu, Roma Yumul, Hongjie Wang, Maximilian Richter, Pavel Sova, Charles Drescher, Pascal Fender, André Lieber
: Defensins are small anti-microbial peptides capable of neutralizing human adenovirus (HAdV) in vitro by binding capsid proteins and blocking endosomal escape of virus. In humans, the alpha defensin HD5 is produced by specialized epithelial cells of the gastro-intestinal and genito-urinary tracts. Here we demonstrate that HD5 is also expressed as an active, secreted peptide by epithelial ovarian and lung cancer cells in situ, in patient biopsies. This finding triggered us to study the role of HD5 in infection and spread of replication-competent, oncolytic HAdV type 3 virus...
January 11, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28077641/chikungunya-influenza-nipah-and-semliki-forest-chimeric-viruses-with-vesicular-stomatitis-virus-actions-in-the-brain
#19
Anthony N van den Pol, Guochao Mao, Anasuya Chattopadhyay, John K Rose, John N Davis
: Recombinant vesicular stomatitis virus (VSV)-based chimeric viruses that include genes from other viruses show promise as vaccines and oncolytic viruses. However, the critical safety concern is the neurotropic nature conveyed by the VSV glycoprotein. VSVs that include the VSV glycoprotein gene, even in most recombinant attenuated strains, can still show substantial adverse or lethal actions in the brain. Here we test 4 chimeric viruses in the brain including those in which glycoprotein genes from Nipah, chikungunya, or influenza H5N1 viruses were substituted for the VSV glycoprotein gene...
January 11, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28077640/viral-rna-at-two-stages-of-reovirus-infection-is-required-for-the-induction-of-necroptosis
#20
Angela K Berger, Bradley E Hiller, Deepti Thete, Anthony J Snyder, Encarnacion Perez, Jason W Upton, Pranav Danthi
: Necroptosis, a regulated form of necrotic cell death requires the activation of the RIP3 kinase. Here, we identify that infection of host cells with reovirus can result in necroptosis. We find that necroptosis requires sensing of the genomic RNA within incoming virus particles via cytoplasmic RNA sensors to produce type I IFN. While these events that occur prior to de novo synthesis of viral RNA are required for induction of necroptosis, they are not sufficient. Induction of necroptosis also requires late stages of reovirus infection...
January 11, 2017: Journal of Virology
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