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Journal of Virology

Bangari Haldipur, Prudhvi Lal Bhukya, Vidya Arankalle, Kavita Lole
Molecular mechanisms of liver pathology and clinical disease in HEV infection remain unclear. MicroRNAs are known to modulate viral pathogenesis either by directly altering viral gene expression or by enhancing cellular antiviral responses. Given the importance of microRNA-122 (miR-122) in liver pathobiology, we investigated possible role of miR-122 in HEV infection. In silico predictions using genotype 1, 2, 3 and 4 HEV sequences showed that majority of genomes (203/222) harbor at least one miR-122/miR-122* target site...
March 14, 2018: Journal of Virology
Susan E Hepp, Gina M Borgo, Simina Ticau, Taro Ohkawa, Matthew D Welch
The baculovirus Autographa californica multiple nucleopolyhedrovirus (AcMNPV), the type species of alphabaculoviruses, is an enveloped DNA virus that infects lepidopteran insects and is commonly known as a vector for protein expression and cell transduction. AcMNPV belongs to a diverse group of viral and bacterial pathogens that target the host cell actin cytoskeleton during infection. AcMNPV is unusual, however, in that it absolutely requires actin translocation into the nucleus early in infection, and actin polymerization within the nucleus late in infection coincident with viral replication...
March 14, 2018: Journal of Virology
Sudhakar Agnihothram, Vineet D Menachery, Boyd L Yount, Lisa C Lindesmith, Trevor Scobey, Alan Whitmore, Alexandra Schäfer, Mark T Heise, Ralph S Baric
Zoonotic viruses circulate as swarms in animal reservoirs and can emerge into human populations causing epidemics that adversely affect public health. Portable, safe, and effective vaccine platforms are needed in the context of these outbreak and emergence situations. In this manuscript, we report the generation and characterization of an alphavirus replicon vaccine platform based on a non-select agent, attenuated Venezuelan equine encephalitis (VEE) virus vaccine strain 3526 (VRP 3526). Using both noroviruses and coronaviruses as model systems, we demonstrate utility of the VRP 3526 platform in generation of recombinant proteins, production of virus like particles, and in vivo efficacy as a vaccine against emergent viruses...
March 14, 2018: Journal of Virology
Steffi De Pelsmaeker, Nicolas Romero, Massimo Vitale, Herman W Favoreel
Natural killer (NK) cells play an important role in the host response against viral infections and cancer development. They are able to kill virus-infected and tumor cells, and produce different important cytokines that stimulate the antiviral and antitumor adaptive immune response, particularly interferon gamma. NK cells are of particular importance in herpesvirus infections, which is illustrated by systemic and life-threatening herpesvirus disease symptoms in patients with deficiencies in NK cell activity, and by the myriad of reports describing herpesvirus NK cell evasion strategies...
March 14, 2018: Journal of Virology
Joanna A Pulit-Penaloza, Joyce Jones, Xiangjie Sun, Yunho Jang, Sharmi Thor, Jessica A Belser, Natosha Zanders, Hannah M Creager, Callie Ridenour, Li Wang, Thomas J Stark, Rebecca Garten, Li-Mei Chen, John Barnes, Terrence M Tumpey, David E Wentworth, Taronna R Maines, C Todd Davis
Influenza A(H1) viruses circulating in swine represent an emerging virus threat as zoonotic infections occur sporadically following exposure to swine. A fatal infection caused by an H1N1 variant (H1N1v) virus was detected in a patient with reported exposure to swine and who presented with pneumonia, respiratory failure, and cardiac arrest. To understand the genetic and phenotypic characteristics of the virus, genome sequence analysis, antigenic characterization, and ferret pathogenesis and transmissibility experiments were performed...
March 14, 2018: Journal of Virology
Peter Bryk, Matthew G Brewer, Brian M Ward
The vaccinia virus protein F13, encoded by the F13L gene, is conserved across the subfamily Chordopoxvirinae and is critical among orthopoxviruses to produce the wrapped form of virus that is required for cell-to-cell spread. F13 is the major envelope protein on the membrane of extracellular forms of virus, however it is not known if F13 is required in steps post-wrapping. In this report, we utilize two temperature-sensitive vaccinia virus mutants from the Condit collection of temperature-sensitive viruses whose small plaque phenotypes have been mapped to the F13L gene...
March 14, 2018: Journal of Virology
John L M Law, Michael Logan, Jason Wong, Juthika Kundu, Darren Hockman, Amir Landi, Chao Chen, Kevin Crawford, Mark Wininger, Janelle Johnson, Catalina Mesa Prince, Elzbieta Dudek, Ninad Mehta, D Lorne Tyrrell, Michael Houghton
Current evidence supports a protective role for virus neutralizing antibodies in immunity against HCV infection. Many cross-neutralizing monoclonal antibodies have been identified. These antibodies have been shown to protect or clear infection in animal models. Previous clinical trials have shown a gpE1/gpE2 vaccine can induce antibodies that neutralize the in vitro infectivity of all the major HCVcc genotypes around the world. However, cross-neutralization appeared to favour certain genotypes with significant but lower neutralization against others...
March 14, 2018: Journal of Virology
Liliana L Cubas-Gaona, Elisabet Diaz-Beneitez, Marina Ciscar, José F Rodríguez, Dolores Rodríguez
Infectious bursal disease virus (IBDV) belongs to the Birnaviridae family and is the etiological agent of a highly contagious and immunosuppressive disease (IBD) that affects domestic chickens ( Gallus gallus ). IBD or Gumboro disease leads to high morbidity and mortality of infected animals, and is responsible for major economic losses to the poultry industry world-wide. IBD is characterized by a massive loss of IgM-bearing B lymphocytes and the destruction of the bursa of Fabricius. The molecular bases of the IBDV pathogenicity are still poorly understood, nonetheless, an exacerbated cytokine immune response and B cell depletion due to apoptosis are considered main factors contributing to the severity of the disease...
March 14, 2018: Journal of Virology
María Cecilia Gimenez, Flavia Adriana Zanetti, Mauricio R Terebiznik, María Isabel Colombo, Laura Ruth Delgui
Birnaviruses are unconventional members of the double-stranded RNA (dsRNA) viruses group that are characterized by the lack of a transcriptionally active inner core. Instead, the birnaviral particles organize their genome in ribonucleoprotein complexes (RNPs) composed by dsRNA segments, the dsRNA-binding VP3 protein, and the viral encoded RNA-dependent RNA-polymerase (RdRp). This and other structural features suggests that birnaviruses may follow a completely different replication program from that followed by members of the Reoviridae family, supporting the hypothesis that birnaviruses are the evolutionary link between single-stranded positive RNA (+ssRNA) and dsRNA viruses...
March 14, 2018: Journal of Virology
Sascha Suffner, Nadine Gerstenberg, Maria Patra, Paula Ruibal, Ahmed Orabi, Michael Schindler, Volker Bruss
During hepatitis B virus infections subviral particles (SVP) consisting only of viral envelope proteins and lipids are secreted. Heterologous expression of the small envelope protein S in mammalian cells is sufficient for SVP generation. S is synthesized as a transmembrane protein with N-terminal (TM1), central (TM2), and C-terminal (HCR) transmembrane domains. The loops between TM1 and TM2 (CL) and between TM2 and HCR (LL) are located in the cytosol and in the ER lumen, respectively. To define domains of S mediating oligomerization during SVP morphogenesis S mutants were characterized by expression in transiently transfected cells...
March 14, 2018: Journal of Virology
Pei Li, Yiwei Shan, Wangliang Zheng, Xiuyuan Ou, Dan Mi, Zhixia Mu, Kathryn V Holmes, Zhaohui Qian
The spike glycoprotein (S) of murine coronavirus mouse hepatitis virus (MHV) strain A59 uses murine carcinoembryonic antigen-related cell adhesion molecule 1a as its receptor for cell entry, but S protein can also be triggered in the absence of receptor by pH 8.0 alone at 37°C. The mechanism by which conformational changes of this S glycoprotein can be triggered by pH 8.0 has not yet been determined. Here we show that MHV-A59 S protein is triggered by pH 8.0 at 37°C to induce receptor-independent syncytium (RIS) formation on 293T cells, and that the conformational changes in S proteins triggered by pH 8...
March 7, 2018: Journal of Virology
Ann J Hessell, Mariya B Shapiro, Rebecca Powell, Delphine C Malherbe, Sean P McBurney, Shilpi Pandey, Tracy Cheever, William F Sutton, Christoph Kahl, Byung Park, Susan Zolla-Pazner, Nancy L Haigwood
A high level of V1V2-specific IgG antibodies in vaccinees' sera was the only independent variable that correlated with a reduced risk of HIV acquisition in the RV144 clinical trial. In contrast, IgG avidity, antibody neutralization, and antibody-dependent cellular cytotoxicity each failed as independent correlates of infection. Extended analyses of RV144 samples demonstrated antiviral activity of V1V2-specific vaccine-induced antibodies. V2-specific antibodies have also been associated with protection from SIV, and the V2i-specific subset of human monoclonal antibodies (mAbs), while poor neutralizers, mediate Fc-dependent antiviral functions in vitro The objective of this study was to determine the protective efficacy of a V2i-specific human mAb 830A against mucosal SHIV challenge...
March 7, 2018: Journal of Virology
Anne B Kristensen, Stephen J Kent, Matthew S Parsons
Antibody Fc-dependent functions are linked to prevention and control of HIV-1 infection. Basic NK cell biology is likely key to understanding the contributions anti-HIV-1 antibody-dependent NK cell activation and cytolysis make to HIV-1 susceptibility and disease progression. The importance of NK cell education through inhibitory receptors specific for self-HLA-I in determining the potency of anti-HIV-1 antibody mediated NK cell activation and cytolysis is controversial. To address this issue more definitively we utilized HLA-I genotyping, flow cytometry staining panels and cytolysis assays to assess the functionality of educated and non-educated peripheral blood NK cells...
March 7, 2018: Journal of Virology
Eryn Blass, Malika Aid, Amanda J Martinot, Rafael A Larocca, Zi Han Kang, Alexander Badamchi-Zadeh, Pablo Penaloza-MacMaster, R Keith Reeves, Dan H Barouch
Natural killer (NK) cells respond rapidly as a first line of defense against infectious pathogens. In addition, NK cells may provide a "rheostat" function and have been shown to reduce the magnitude of antigen-specific T cell responses following infection to avoid immunopathology. However, it remains unknown whether NK cells similarly modulate vaccine-elicited T cell responses following viral challenge. We used the LCMV clone 13 infection model to address whether NK cells regulate T cell responses in adenovirus vector vaccinated mice following challenge...
March 7, 2018: Journal of Virology
Yi Xu, Ho Jung Ju, S DeBlasio, Elizabeth J Carino, R Johnson, M MacCoss, M Cilia Heck, W Allen Miller, S M Gray
Translational readthrough of the stop codon of the capsid protein (CP) open reading frame (ORF) is used by members of the Luteoviridae to produce their minor capsid protein as a readthrough protein (RTP). The elements regulating RTP expression are not well understood, but involve long-distance interactions between RNA domains. Using high-resolution mass spectrometry, glutamine and tyrosine were identified as the primary amino acids inserted at the stop codon of Potato leafroll virus (PLRV) CP ORF. We characterized the contributions of a cytidine-rich domain immediately downstream, and a branched stem-loop structure 600-700 nucleotides downstream of the CP stop codon...
March 7, 2018: Journal of Virology
Shannan D Washington, Samantha I Edenfield, Caroline Lieux, Zachary L Watson, Sean M Taasan, Adit Dhummakupt, David C Bloom, Donna M Neumann
Herpes Simplex Virus 1 (HSV-1) establishes a lifelong latent infection in host peripheral neurons including the neurons of the trigeminal ganglia (TG). HSV-1 can reactivate from neurons to cause recurrent infection. During latency, the insulator protein CTCF occupies DNA binding sites on the HSV-1 genome and these sites have been previously characterized as functional enhancer-blocking insulators. Previously, CTCF was found to be dissociated from wild type virus post-reactivation but not in mutants that do not reactivate, indicating that CTCF eviction may also be an important component of reactivation...
March 7, 2018: Journal of Virology
Jing Shi, Ran Xiong, Tao Zhou, Peiyi Su, Xihe Zhang, Xusheng Qiu, Hongmei Li, Sunan Li, Changqing Yu, Bin Wang, Chan Ding, Thomas E Smithgall, Yong-Hui Zheng
The primate lentiviral accessory protein Nef downregulates CD4 and MHC-I from the cell surface via independent endosomal trafficking pathways to promote viral pathogenesis. In addition, Nef antagonizes a novel restriction factor, SERINC5 (Ser5), to increase viral infectivity. To explore the molecular mechanism of Ser5 antagonism by Nef, we determined how Nef affects Ser5 expression and intracellular trafficking in comparison with CD4 and MHC-I. We confirm that Nef excludes Ser5 from HIV-1 virions by downregulating its cell surface expression via similar functional motifs required for CD4-downregulation...
March 7, 2018: Journal of Virology
Tongtong Wang, Qian Du, Xingchen Wu, Yingying Niu, Lijuan Guan, Zhenyu Wang, Xiaomin Zhao, Shan-Lu Liu, Dewen Tong, Yong Huang
Porcine circovirus type 2 (PCV2) capsid protein (Cap) is a unique structure protein that plays pivotal roles in the process of viral replication and pathogenesis. Herein, we characterized putative porcine Makorin ring finger protein 1 variant (pMKRN1), a N-terminal-truncated variant of putative full-size porcine MKRN1, which is a unique expression pattern resulting from the porcine mkrn1 gene and interacts with PCV2 Cap. Domain mapping assay showed that the C terminus of pMKRN1 and the fragments (108-198 aa) of Cap are required for this interaction...
March 7, 2018: Journal of Virology
Adrián Lázaro-Frías, Sergio Gómez-Medina, Lucas Sánchez-Sampedro, Karl Ljungberg, Mart Ustav, Peter Liljeström, César Muñoz-Fontela, Mariano Esteban, Juan García-Arriaza
Zaire and Sudan ebolavirus species cause a severe disease in humans and non-human primates (NHPs) characterized by high mortality rate. There are no licensed therapies or vaccines against Ebola virus disease (EVD), and the recent 2013-2016 outbreak in West Africa highlighted the need of EVD-specific medical countermeasures. Here, we have generated and characterized head-to-head the immunogenicity and efficacy of five vaccine candidates against Zaire ebolavirus (EBOV) and Sudan ebolavirus (SUDV) based on the highly attenuated poxvirus vector modified vaccinia virus Ankara (MVA), expressing either the virus glycoprotein (GP) or GP together with the virus protein 40 (VP40) forming virus-like particles (VLPs)...
March 7, 2018: Journal of Virology
Yanmin Wan, Guobin Kang, Chithra Sreenivasan, Lance Daharsh, Junfeng Zhang, Wenjin Fan, Dan Wang, Hideaki Moriyama, Feng Li, Qingsheng Li
Two lineages of Influenza D virus (IDV) have been found to infect cattle and promote bovine respiratory disease complex (BRDC), one of the most commonly diagnosed causes of morbidity and mortality within the cattle industry. Furthermore, IDV can infect other economically important domestic livestock including pigs and has the potential to infect humans, which necessitates the need for an efficacious vaccine. In this study, we designed a DNA vaccine expressing consensus hemagglutinin-esterase-fusion (HEF) protein (FluD-Vax) and tested its protective efficacy against two lineages of IDV (D/OK and D/660) in guinea pigs...
March 7, 2018: Journal of Virology
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