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Journal of Virology

Yanyan Ke, Wai Nam Liu, Zhisheng Her, Min Liu, Sue Yee Tan, Yong Wah Tan, Xue Ying Chan, Yong Fan, Edwin Kunxiang Huang, Huiyi Chen, Kenneth Tou En Chang, Jerry Kok Yen Chan, Justin Jang Hann Chu, Qingfeng Chen
Since the discovery of enterovirus-A71 (EV-A71) half a century ago, it has caused large-scale outbreaks of hand-foot-and-mouth disease worldwide, in particular in the Asia-Pacific region, causing a great concern of public health and economic burden. Detailed mechanisms on the modulation of immune responses after EV-A71 infection have not been fully known, and the lack of appropriate models hinders the development of promising vaccines and drugs. In the present study, NOD- scid IL2Rγ-/- (NSG) mice with human immune system (humanized mice) at the age of four-week-old were found to be susceptible to a human isolate of EV-A71 infection...
November 14, 2018: Journal of Virology
Hiresh Ayoubian, Nicole Ludwig, Tobias Fehlmann, Jennifer Menegatti, Laura Gröger, Eleni Anastasiadou, Pankaj Trivedi, Andreas Keller, Eckart Meese, Friedrich A Grässer
Diffuse large B-cell lymphoma (DLBCL) is an aggressive lymphoid tumor which is occasionally Epstein-Barr virus (EBV)-positive and is further subtyped as activated B-cell (ABC) and germinal center B-cell (GCB) DLBCL, which has implications for prognosis and treatment.We performed Ago2-RNA immunoprecipitation followed by high throughput RNA sequencing (Ago2-RIP-Seq) to capture functionally active miRNAs in EBV-negative ABC-DLBCL and GC-DLBCL cell lines and their EBV-infected counterparts. In parallel, total miRNomes of these cells were sequenced to capture the cellular miRNA profile for comparison with the functionally active profile...
November 14, 2018: Journal of Virology
James D Allen, Hyesun Jang, Joshua DiNapoli, Harold Kleanthous, Ted M Ross
The vast majority of people already have pre-existing immune responses to influenza viruses from one or more subtypes. However, almost all preclinical studies evaluate new influenza vaccine candidates in immunologically naïve animals. Recently, our group demonstrated that priming naive ferrets with broadly reactive H1 COBRA HA based vaccines boosted pre-existing antibodies induced by wild-type H1N1 virus infections. These H1 COBRA HA antigens induced antibodies with HAI activity against multiple antigenically different H1N1 viral variants...
November 14, 2018: Journal of Virology
Tetsuya Yoshida, Takuya Shiraishi, Yuka Hagiwara-Komoda, Ken Komatsu, Kensaku Maejima, Yukari Okano, Yuji Fujimoto, Akira Yusa, Yasuyuki Yamaji, Shigetou Namba
Understanding the innate immune mechanisms of plants is necessary for breeding of disease-resistant lines. Previously, we identified the antiviral resistance gene JAX1 from Arabidopsis thaliana , which inhibits infection by potexviruses. JAX1 encodes a unique jacalin-type lectin protein. In this study, we analyzed the molecular mechanisms of JAX1-mediated resistance. JAX1 restricted the multiplication of a potexviral replicon lacking movement-associated proteins, suggesting inhibition of viral replication. Therefore, we developed an in vitro potato virus X (PVX) translation/replication system using vacuole- and nucleus-free lysates from tobacco protoplasts, and revealed that JAX1 inhibits viral RNA synthesis but not translation of the viral RNA-dependent RNA polymerase (RdRp)...
November 14, 2018: Journal of Virology
Kasen K Riemersma, Cody Steiner, Anil Singapuri, Lark L Coffey
Chikungunya virus (CHIKV) is a re-emerging global health threat that produces debilitating arthritis in people. Like other RNA viruses with high mutation rates, CHIKV produces populations of genetically diverse genomes within a host. While several known CHIKV mutations influence disease severity in vertebrates and transmission by mosquitoes, the role of intrahost diversity in chikungunya arthritic disease is not studied. In this study, high and low fidelity CHIKV variants, previously characterized by altered in vitro population mutation frequencies, were used to evaluate how intrahost diversity influences clinical disease, CHIKV replication, and antibody neutralization in immunocompetent adult mice inoculated in the rear footpads...
November 14, 2018: Journal of Virology
Markus Hoffmann, Inga Nehlmeier, Constantin Brinkmann, Verena Krähling, Laura Behner, Anna-Sophie Moldenhauer, Nadine Krüger, Julia Nehls, Michael Schindler, Thomas Hoenen, Andrea Maisner, Stephan Becker, Stefan Pöhlmann
Ebola virus (EBOV) and Nipah virus (NiV) infection of humans can cause fatal disease and constitutes a public health threat. In contrast, EBOV and NiV infection of fruit bats, the putative (EBOV) or proven (NiV) natural reservoir, is not associated with disease and it is currently unknown how these animals control the virus. The human interferon (IFN)-stimulated antiviral effector protein tetherin (CD317, BST-2) blocks release of EBOV- and NiV-like particles from cells and is counteracted by the EBOV glycoprotein (GP)...
November 14, 2018: Journal of Virology
Luis Enrique Sandoval, Hongbing Jiang, David Wang
Orsay virus is the only known natural virus pathogen of Caenorhabditis elegans , and its discovery has enabled virus-host interactions studies in this model organism. Host genes required for viral infection remain understudied. We previously established a forward genetic screen based on a virus-inducible GFP transcriptional reporter to identify novel host factors essential for virus infection. Here we report the essential role in Orsay virus infection of the Dietary Restriction-Like ( drl-1 ) gene, which encodes a serine/threonine kinase similar to the mammalian MEKK3 kinase...
November 14, 2018: Journal of Virology
Luis R Castillo-Menendez, Hanh T Nguyen, Joseph Sodroski
Binding to the receptor, CD4, triggers entry-related conformational changes in the human immunodeficiency virus (HIV-1) envelope glycoprotein (Env) trimer ((gp120/gp41)3 ). Soluble versions of HIV-1 Env trimers (sgp140 SOSIP.664) stabilized by a gp120-gp41 disulfide bond and a change (I559P) in gp41 have been structurally characterized. Here we use crosslinking/mass spectrometry to evaluate the conformations of functional membrane Env and sgp140 SOSIP.664. Differences were detected in the gp120 trimer association domain and C-terminus and in the gp41 heptad repeat (HR1) region...
November 14, 2018: Journal of Virology
Sai Priya Anand, Jérémie Prévost, Sophie Baril, Jonathan Richard, Halima Medjahed, Jean-Philippe Chapleau, William D Tolbert, Sharon Kirk, Amos B Smith, Bruce D Wines, Stephen J Kent, P Mark Hogarth, Matthew S Parsons, Marzena Pazgier, Andrés Finzi
HIV-1 conceals epitopes of its envelope glycoproteins (Env) recognized by antibody-dependent cellular cytotoxicity (ADCC)-mediating antibodies. These antibodies (Abs), including anti-co-receptor binding site (CoRBS) and anti-cluster A, preferentially recognize Env in its "open" conformation. The binding of anti-CoRBS Abs has been shown to induce conformational changes that further opens Env allowing interaction of anti-cluster A antibodies. We explored the possibility that CoRBS Abs synergize with anti-cluster A Abs to engage Fc-gamma receptors to mediate ADCC...
November 14, 2018: Journal of Virology
Benedikt Asbach, Karen V Kibler, Josef Köstler, Beatriz Perdiguero, Nicole L Yates, Sherry Stanfield-Oakley, Georgia D Tomaras, Shing-Fen Kao, Kathryn E Foulds, Mario Roederer, Michael S Seaman, David C Montefiori, Robert Parks, Guido Ferrari, Donald N Forthal, Sanjay Phogat, James Tartaglia, Susan W Barnett, Steven G Self, Raphael Gottardo, Anthony D Cristillo, Deborah E Weiss, Lindsey Galmin, Song Ding, Jonathan L Heeney, Mariano Esteban, Bertram L Jacobs, Giuseppe Pantaleo, Ralf Wagner
The use of heterologous immunization regimens and improved vector systems has led to increases in immunogenicity of HIV-1 vaccine candidates in non-human primates. In order to resolve interrelations between different delivery modalities, three different poxvirus boost regimens were compared. Three groups of rhesus macaques were each primed with the same DNA vaccine encoding for Gag, PolNef, and gp140. The groups were then boosted either with the vaccinia virus strain NYVAC or a variant with improved replication competence in human cells termed NYVAC-KC...
November 14, 2018: Journal of Virology
Huansheng Wu, Liuyuan Shi, Yina Zhang, Xiran Peng, Tuyuan Zheng, Yahui Li, Boli Hu, Xiaojuan Zheng, Jiyong Zhou
Ubiquitination is critical for several cellular physical processes. However, ubiquitin modification in virus replication is poorly understood. Therefore, the present study aimed to determine the presence and effect of ubiquitination on polymerase activity of viral protein 1 (VP1) of avibirnavirus. We reported that the replication of avibirnavirus is regulated by ubiquitination of its VP1 protein, the RNA-dependent RNA polymerase of infectious bursal disease virus (IBDV). In vivo detection revealed the ubiquitination of VP1 protein in IBDV infected target organs and different cells, but not in purified IBDV particles...
November 14, 2018: Journal of Virology
Aaron P Roznowski, Robert J Young, Samuel D Love, Avenetti A Andromita, Vanessa A Guzman, Margaret H Wilch, Ava Block, Anne McGill, Martine Lavelle, Anastasia Romanova, Aimi Sekiguchi, Meixiao Wang, April D Burch, Bentley A Fane
Although microviruses do not possess a visible tail structure, one vertex rearranges after interacting with host lipopolysaccharides. Most examinations of host range, eclipse, and penetration were conducted before this "host-induced" unique vertex was discovered and before DNA sequencing became routine. Consequently, structure-function relationships dictating host range remain undefined. Biochemical and genetic analyses were conducted with two closely related microviruses, α3 and ST-1. Despite ∼90% amino acid identity, the natural host of α3 is E...
November 14, 2018: Journal of Virology
Karen V Kibler, Benedikt Asbach, Beatriz Perdiguero, Juan García-Arriaza, Nicole L Yates, Robert Parks, Sherry Stanfield-Oakley, Guido Ferrari, David C Montefiori, Georgia D Tomaras, Mario Roederer, Kathryn E Foulds, Donald N Forthal, Michael S Seaman, Steve Self, Raphael Gottardo, Sanjay Phogat, James Tartaglia, Susan Barnett, Anthony D Cristillo, Deborah Weiss, Lindsey Galmin, Song Ding, Jonathan L Heeney, Mariano Esteban, Ralf Wagner, Giuseppe Pantaleo, Bertram L Jacobs
As part of the continuing effort to develop an effective HIV vaccine, we generated a poxviral vaccine vector (previously described) designed to improve on the results of the RV144 Phase III clinical trial. The construct, NYVAC-KC, is a replication-competent, attenuated recombinant of the vaccinia virus strain, NYVAC. NYVAC is a vector that has been used in many previous clinical studies but is replication deficient. Here we report a side-by-side comparison of replication-restricted NYVAC and replication-competent NYVAC-KC in a non-human primate study, which utilized a prime-boost regimen similar to that of RV144...
November 14, 2018: Journal of Virology
Sanjeev Kumar, Harekrushna Panda, Muzamil Ashraf Makhdoomi, Nitesh Mishra, Haaris Ahsan Safdari, Himanshi Chawla, Heena Aggarwal, Elluri Seetharami Reddy, Rakesh Lodha, Sushil Kumar Kabra, Anmol Chandele, Somnath Dutta, Kalpana Luthra
Broadly neutralizing antibodies (bNAbs) have demonstrated protective effects against HIV-1 in primate studies and recent human clinical trials. Elite-neutralizers are potential candidates for isolation of HIV-1 bNAbs. The coexistence of bNAbs such as BG18 with neutralization susceptible autologous viruses in an HIV-1 infected adult elite controller has been suggested to control viremia. Disease progression is faster in HIV-1 infected children than adults. Plasma bNAbs with multiple epitope specificities are developed in HIV-1 chronically infected children with more potency and breadth than in adults...
November 14, 2018: Journal of Virology
Cindy Nürnberger, Bianca S Bodmer, Anna H Fiedler, Gülsah Gabriel, Michael D Mühlebach
The impact of the Zika virus (ZIKV) epidemic highlights the need for vaccines that reduce or prevent infection and reliably prevent teratogenic complications. The live-attenuated measles virus (MV) vaccine strains are a promising vaccine platform since they induce robust humoral and cellular immune responses against additional antigens and have an excellent safety record. To explore its potential to protect against ZIKV, we compared a recombinant Schwarz strain MV that encodes ZIKV prM and soluble E proteins (MV-Zika-sE) with a prototypic alum-adjuvanted whole-inactivated ZIKV particle vaccine...
November 14, 2018: Journal of Virology
Kwangchol Mun, Tanel Punga
Human adenovirus (HAdV) encodes a multifunctional DNA-binding protein pVII, which is involved in virus DNA packaging and extracellular immune signaling regulation. Although the pVII is an essential viral protein, its exact role in the virus life cycle and interplay with cellular proteins have remained to a large extent unclear. We have recently identified the cellular zinc finger protein 622 (ZNF622) as a potential pVII-interacting protein. In this study, we describe the functional consequences of the ZNF622-pVII interplay and the role of ZNF622 in the HAdV life cycle...
November 14, 2018: Journal of Virology
Joshua A Hill, Minako Ikoma, Danielle M Zerr, Ryan S Basom, Vikas Peddu, Meei-Li Huang, Ruth Hall Sedlak, Keith R Jerome, Michael Boeckh, Serge Barcy
Human herpesvirus 6B (HHV-6B) DNA is frequently detected in human samples. Diagnostic assays distinguishing HHV-6B reactivation from latency are limited. This has impaired strategies to diagnose and treat HHV-6B-associated diseases. We used RNA sequencing to characterize and compare the HHV-6B transcriptome in multiple sample types, including 1) whole blood from hematopoietic cell transplant (HCT) recipients with and without HHV-6B plasma viremia; 2) tumor tissue samples from subjects with large B cell lymphoma infected with HHV-6B; 3) lymphoblastoid cell lines (LCLs) from subjects with inherited chromosomally integrated HHV-6B or latent infection with HHV-6B; and 4) HHV-6B Z29 infected SupT1 CD4+ T cells...
November 14, 2018: Journal of Virology
Kendra A Bussey, Sripriya Murthy, Elisa Reimer, Baca Chan, Bastian Hatesuer, Klaus Schughart, Britt Glaunsinger, Heiko Adler, Melanie M Brinkmann
Murine gammaherpesvirus 68 (MHV68) is an amenable small animal model for study of the human pathogens Epstein-Barr virus and Kaposi's sarcoma-associated herpesvirus. Here, we have characterized the roles of the endosomal TLR escort protein UNC93B, endosomal TLR7, 9, and 13, and cell surface TLR2 in MHV68 detection. We found that the interferon α (IFNα) response of plasmacytoid dendritic cells (pDC) to MHV68 was reduced in Tlr9-/- cells compared to wildtype (WT), but not completely lost. Tlr7-/- pDC responded similarly to WT...
November 14, 2018: Journal of Virology
Jianxiang Qiu, Zhimin Tang, Yi Cai, Wenbi Wu, Meijin Yuan, Kai Yang
Alphabaculoviruses are lepidopteran-specific nucleopolyhedroviruses that replicate within the nucleus; however, the anterograde transport of the nucleocapsids of these viruses, which is an obligatory step for progeny virion production, is not well understood. In the present study, a unique Alphabaculovirus gene with unknown function, namely, the Autographa californica multiple nucleopolyhedrovirus (AcMNPV) ac51 gene, was found to be required for efficient nuclear egress of AcMNPV nucleocapsids. Our results indicate that ac51 is a late gene, and Ac51 protein was detectable from 24 to 72 h postinfection using an antibody raised against Ac51...
November 14, 2018: Journal of Virology
Erin Harvey, Karrie Rose, John-Sebastian Eden, Nathan Lo, Thilanka Abeyasuriya, Mang Shi, Stephen L Doggett, Edward C Holmes
Understanding the microbiome of ticks in Australia is of considerable interest given the ongoing debate over whether Lyme disease, and its causative agent the bacterium Borrelia burgdorferi sensu lato, are present in Australia. The diversity of bacteria infecting Australian ticks has been studied using both culture and metagenomics based techniques. However, little is known about the virome of Australian ticks, including whether this includes viruses with the potential to infect mammals. We used a meta-transcriptomics approach to reveal the diversity and evolution of viruses from Australian ticks collected from two locations on the central-east coast of Australia, including metropolitan Sydney...
November 7, 2018: Journal of Virology
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