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Christina N Como, Catherine M Pearce, Randall J Cohrs, Nicholas L Baird
Varicella zoster virus (VZV) is a neurotropic alphaherpesvirus that, following primary infection (varicella), establishes latency in sensory, autonomic, sympathetic and parasympathetic neurons, where it remains until reactivation (zoster). VZV-specific cell-mediated immune responses maintain VZV latency; thus, immunosuppressed and elderly persons are at risk of reactivation and associated neurological diseases. However, the cytokines produced by the immune system that control VZV in neurons are largely unknown...
July 3, 2018: Virology
Sabari Nath Neerukonda, Upendra K Katneni, Matthew Bott, Serguei P Golovan, Mark S Parcells
Marek's disease (MD) is a pathology of chickens associated with paralysis, immune suppression, and the rapid formation of T-cell lymphomas. MD is caused by the herpesvirus, Marek's disease virus (MDV). We examined endoplasmic reticulum (ER) stress and the activation of unfolded protein response (UPR) pathways during MDV infection of cells in culture and lymphocytes in vivo. MDV strains activate the UPR as measured by increased mRNA expression of GRP78/BiP with concomitant XBP1 splicing and induction of its target gene, EDEM1...
July 3, 2018: Virology
Matthew F Lawrance, Katherine L Mansfield, Emma Sutton, Anna E Savage
Chelonid Alphaherpesvirus 5 (ChHV5) has long been associated with fibropapillomatosis (FP) tumor disease in marine turtles. Presenting primarily in juvenile animals, FP results in fibromas of the skin, connective tissue, and internal organs, which may indirectly affect fitness by obstructing normal turtle processes. ChHV5 is near-universally present in tumorous tissues taken from affected animals, often at very high concentrations. However, there is also considerable asymptomatic carriage amongst healthy marine turtles, suggesting that asymptomatic hosts play an important role in disease ecology...
June 28, 2018: Virology
Hsiao-Yun Shao, Ying-Chin Chen, Nai-Hsiang Chung, Yi-Ju Lu, Ching-Kun Chang, Shu-Ling Yu, Chia-Chyi Liu, Yen-Hung Chow
We evaluated the efficacy of a recombinant adenovirus that expresses a membrane-truncated respiratory syncytial virus (RSV) fusion protein (Ad-F0ΔTM) in newborns via maternal immunization (MI) of pregnant cotton rats. Intranasal Ad-F0ΔTM immunization was given to pregnant female rats, and MI-newborn rats were then challenged intranasally with RSV. Anti-RSV IgGs were observed in the serum of MI-newborn rats after birth. The pulmonary viral loads in Ad-F0ΔTM vs. control vector, Ad-LacZ, and MI-newborns on day 3 post-challenge were reduced by 4 log10 /g lung...
June 28, 2018: Virology
James Weger-Lucarelli, Claudia Rückert, Nathan D Grubaugh, Michael J Misencik, Philip M Armstrong, Mark D Stenglein, Gregory D Ebel, Doug E Brackney
Mosquito cell lines have been used extensively in research to isolate and propagate arthropod-borne viruses and understand virus-vector interactions. Despite their utility as an in vitro tool, these cell lines are poorly defined and may harbor insect-specific viruses. Accordingly, we screened four commonly-used mosquito cell lines, C6/36 and U4.4 cells from Aedes albopictus, Aag2 cells from Aedes aegypti, and Hsu cells from Culex quinquefasciatus, for the presence of adventitious (i.e. exogenous) viruses. All four cell lines stained positive for double-stranded RNA, indicative of RNA virus replication...
June 26, 2018: Virology
Jing Guo, Xianxian Liu, Chuanjian Wu, Jingping Hu, Ke Peng, Li Wu, Sidong Xiong, Chunsheng Dong
HIV-1 hijacks host classical cargo nuclear transportation, or nonclassical pathways by directly interacting with importin-β family proteins or nucleoporins for efficient pre-integration complex (PIC) nuclear import. Recently, an N-terminal truncated form of nucleoporin Pom121c (601-987 aa) was reported to inhibit HIV-1 replication. In contrast, we found that HIV-1 replication was significantly decreased in 293T and TZM-b1 cells with siRNA-mediated Pom121 knockdown. Quantitative PCR indicated that viral replication was impaired at the step of cDNA nuclear import...
June 25, 2018: Virology
Dane Bowder, Haley Hollingsead, Kate Durst, Duoyi Hu, Wenzhong Wei, Joshua Wiggins, Halima Medjahed, Andrés Finzi, Joseph Sodroski, Shi-Hua Xiang
The V3 loop of the human immunodeficiency virus type 1 (HIV-1) gp120 exterior envelope glycoprotein (Env) becomes exposed after CD4 binding and contacts the coreceptor to mediate viral entry. Prior to CD4 engagement, a hydrophobic patch located at the tip of the V3 loop stabilizes the non-covalent association of gp120 with the Env trimer of HIV-1 subtype B strains. Here, we show that this conserved hydrophobic patch (amino acid residues 307, 309 and 317) contributes to gp120-trimer association in HIV-1 subtype C, HIV-2 and SIV...
June 21, 2018: Virology
Dayna Mason, Xiaoying Zhang, Tânia Monteiro Marques, Barbara Rose, Samantha Khoury, Meredith Hill, Fiona Deutsch, J Guy Lyons, Margarida Gama-Carvalho, Nham Tran
Human papillomavirus (HPV), notably type 16, is a risk factor for up to 75% of oropharyngeal squamous cell carcinomas (SCC). It has been demonstrated that small non-coding RNAs known as microRNAs play a vital role in the cellular transformation process. In this study, we used an LNA array to further investigate the impact of HPV16 on the expression of microRNAs in oropharyngeal (tonsillar) cancer. A number of miRNAs were found to be deregulated, with miR-496 showing a four-fold decrease. Over-expression of the high risk E6 oncoprotein down-regulated miR-496, impacting upon the post-transcriptional control of the transcription factor E2F2...
June 20, 2018: Virology
James Weger-Lucarelli, Selene M Garcia, Claudia Rückert, Alex Byas, Shelby L O'Connor, Matthew T Aliota, Thomas C Friedrich, David H O'Connor, Gregory D Ebel
Arboviruses such as Zika virus (ZIKV, Flaviviridae; Flavivirus) must replicate in both mammalian and insect hosts possessing strong immune defenses. Accordingly, transmission between and replication within hosts involves genetic bottlenecks, during which viral population size and genetic diversity may be significantly reduced. To help quantify these bottlenecks and their effects, we constructed 4 "barcoded" ZIKV populations that theoretically contain thousands of barcodes each. After identifying the most diverse barcoded virus, we passaged this virus 3 times in 2 mammalian and mosquito cell lines and characterized the population using deep sequencing of the barcoded region of the genome...
June 20, 2018: Virology
Laura J Adkins, Caitlyn T Molloy, Jason B Weinberg
CD8 T cells play a key role in clearance of mouse adenovirus type 1 (MAV-1) from the lung and contribute to virus-induced airway inflammation. We tested the hypothesis that interactions between Fas ligand (FasL) and Fas mediate the antiviral and proinflammatory effects of CD8 T cells. FasL and Fas expression were increased in the lungs of C57BL/6 (B6) mice during MAV-1 respiratory infection. Viral replication and weight loss were similar in B6 and Fas-deficient (lpr) mice. Histological evidence of pulmonary inflammation was similar in B6 and lpr mice, but lung mRNA levels and airway proinflammatory cytokine concentrations were lower in MAV-1-infected lpr mice compared to infected B6 mice...
June 13, 2018: Virology
Qiang Li, Junnai Wang, Daiqing Liao, Jihui Ai, Lei Jin, Qinglei Gao
Adenovirus E1B 55-kilodalton (E1B-55K) mediated DAXX degradation represents a potential mechanism by which E1B-55K sensitizes cancer cells to chemotherapy. Here we report the effects of E1B-55K-mediated DAXX degradation in chemoresistant ovarian cancer cells on response to chemotherapy. Cells with E1B-55K expression were more sensitive to cisplatin than cells without E1B-55K expression. In vivo C13* xenograft studies showed that the combination of cisplatin and E1B-55K was markedly more effective to slow tumor growth and to confer prolonged survival of tumor-bearing mice than either cisplatin or E1B-55K alone...
June 12, 2018: Virology
Růžena Píchalová, Tibor Füzik, Barbora Vokatá, Michaela Rumlová, Manuel Llano, Alžběta Dostálková, Ivana Křížová, Tomáš Ruml, Pavel Ulbrich
Retrovirus assembly is driven mostly by Gag polyprotein oligomerization, which is mediated by inter and intra protein-protein interactions among its capsid (CA) domains. Mason-Pfizer monkey virus (M-PMV) CA contains three cysteines (C82, C193 and C213), where the latter two are highly conserved among most retroviruses. To determine the importance of these cysteines, we introduced mutations of these residues in both bacterial and proviral vectors and studied their impact on the M-PMV life cycle. These studies revealed that the presence of both conserved cysteines of M-PMV CA is necessary for both proper assembly and virus infectivity...
June 12, 2018: Virology
Bianca S Bodmer, Anna H Fiedler, Jan R H Hanauer, Steffen Prüfer, Michael D Mühlebach
Cases of Middle East respiratory syndrome coronavirus (MERS-CoV) continue to occur, making it one of the WHO´s targets for accelerated vaccine development. One vaccine candidate is based on live-attenuated measles virus (MV) vaccine encoding the MERS-CoV spike glycoprotein (MERS-S). MVvac2 -MERS-S(H) induces robust humoral and cellular immunity against MERS-S mediating protection. Here, the induction and nature of immunity after vaccination with MVvac2 -MERS-S(H) or novel MVvac2 -MERS-N were further characterized...
June 11, 2018: Virology
Dagmar Čížková, Stuart J E Baird, Jana Těšíková, Sebastian Voigt, Ďureje Ľudovít, Jaroslav Piálek, Joëlle Goüy de Bellocq
Murine cytomegalovirus (MCMV) has been reported from house mice (Mus musculus) worldwide, but only recently from Eastern house mice (M. m. musculus), of particular interest because they form a semi-permeable species barrier in Europe with Western house mice, M. m. domesticus. Here we report genome sequences of EastMCMV (from Eastern mice), and set these in the context of MCMV genomes from genus Mus hosts. We show EastMCMV and WestMCMV are genetically distinct. Phylogeny splitting analyses show a genome wide (94%) pattern consistent with no West-East introgression, the major exception (3...
June 9, 2018: Virology
Tian-Pei Guan, Jade L L Teng, Kai-Yan Yeong, Zhang-Qiang You, Hao Liu, Samson S Y Wong, Susanna K P Lau, Patrick C Y Woo
The Sichuan takin inhabits the bamboo forests in the Eastern Himalayas and is considered as a national treasure of China with the highest legal protection and conservation status considered as vulnerable according to The IUCN Red List of Threatened Species. In this study, fecal samples of 71 Sichuan takins were pooled and deep sequenced. Among the 103,553 viral sequences, 21,961 were assigned to mammalian viruses. De novo assembly revealed genomes of an enterovirus and an astrovirus and contigs of circoviruses and genogroup I picobirnaviruses...
June 7, 2018: Virology
Xiaojuan Zhu, Tao Wu, Ying Chi, Yiyue Ge, Bin Wu, Minghao Zhou, Fengcai Zhu, Minjun Ji, Lunbiao Cui
Enterovirus A71 (EV-A71) infection can cause hand, foot and mouth disease (HFMD), and even fatal meningoencephalitis. Unfortunately, there is currently no effective treatment for EV-A71 infection due to the lack of understanding of the mechanism of neurological diseases. In this study, we employed SH-SY5Y human neuroblastoma cells to explore the roles of caspase-1 in neuropathogenesis. The expression and activity of caspase-1 were analyzed. The potential immuneconsequences mediated by caspase-1 including cell death, lysis, DNA degradation, and secretion of pro-inflammatory were also examined...
June 7, 2018: Virology
Marsha DeSmet, Sriramana Kanginakudru, Leny Jose, Fang Xie, Timra Gilson, Elliot J Androphy
The papillomavirus (PV) E2 protein activates transcription and replication by recruiting cellular proteins and the E1 DNA helicase to their binding sites in the viral genome. We recently demonstrated that phosphorylation of tyrosine 102 in the bovine papillomavirus (BPV-1) E2 protein restricts these activities and that fibroblast growth factor receptor-3 (FGFR3) tyrosine kinase binds PV E2. Expression of FGFR3 decreased viral replication with both wild-type and the phenylalanine substitution at position 102, inferring that another kinase targets Y102...
June 6, 2018: Virology
Nayeli Aguilar-Hernández, Susana López, Carlos F Arias
Human astrovirus is an important etiological agent of acute gastroenteritis in young children. Despite advances in the characterization of the structure of the virion by cryo-electron microscopy and of capsid proteins by x-ray crystallography, the definition of the minimal polypeptide composition of infectious virus particles has been elusive. In this work we show that mature infectious particles are composed by only two proteins; VP34 that forms the core domain of the virus, and VP27 that constitutes the 30 dimeric spikes present on the virus surface...
June 5, 2018: Virology
Feiyu Hong, Jana L Jacobs, Evgenia Aga, Anthony R Cillo, Elizabeth Fyne, Dianna L Koontz, Lu Zheng, John W Mellors
The relationships between HIV-1 DNA copy number, proviral transcriptional activity, and residual plasma viremia in individuals off and on ART are not well defined. To address this, we performed a cross-sectional study of 12 viremic donors and 23 ART-treated virologically suppressed (plasma HIV-1 RNA<20 copies/ml) donors. We report a strong association between HIV-1 DNA copy number and HIV-1 transcriptional activity in blood that persists on suppressive ART, but not between transcriptional activity and the levels of persistent viremia on ART...
June 4, 2018: Virology
Uddhav Timilsina, Dibya Ghimire, Laxmi Prasad Adhikari, Abhi Bhattarai, Nawneet Mishra, Madhu Rai, Ravi Chandra Dubey, Ritu Gaur
HIV-1 Maturation inhibitors (MIs) bind to the C-terminal domain of capsid protein (CA-CTD) and spacer peptide 1 (SP1) in HIV-1 Gag and inhibit the CA-SP1 cleavage by stabilizing the immature Gag. The β-turn motif, GVGGP in the HIV CA-CTD (residues 220-224) is one of the key determinants of HIV Gag assembly. In the present study, we mutated each residue of HIV-1 β-turn motif to alanine and observed complete inhibition of virus release of all mutants. This defect in virus release was rescued in the presence of maturation inhibitors; BVM and PF-46396 for P224A mutant...
June 4, 2018: Virology
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