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Journal of Virology

Robert van Domselaar, Duncan T Njenda, Rohit Rao, Anders Sönnerborg, Kamalendra Singh, Ujjwal Neogi
Human immunodeficiency virus type 1 subtype C (HIV-1C) has a natural deletion of a YPxL motif in its Gag-p6 late domain. This domain mediates the binding of Gag to host cell protein ALIX and subsequently facilitates viral budding. In a subset of HIV-1C infected individuals, the tetrapeptide insertion PYxE has been identified at the deleted YPxL motif site. Here, we report the consequences of PYxE insertion on the interaction with ALIX and the relevance regarding replication fitness and drug sensitivity. In our three HIV-1C cohorts, PYKE and PYQE were most prevalent among PYxE variants...
February 13, 2019: Journal of Virology
Lori McGinnes Cullen, Madelyn R Schmidt, Trudy G Morrison
Most individuals are infected with respiratory syncytial virus (RSV) by age two, but infection does not result in long-term protective immunity to subsequent infections. Previous RSV infection may, however, impact responses to an RSV vaccine. The goal of these studies was to explore the effect of previous RSV infection on murine antibody responses to RSV F and G protein containing virus-like particles (VLP), comparing responses to those resulting from VLP immunization of RSV naïve animals. These studies showed that after RSV infection, immunization with a single dose of VLPs containing a conformation stabilized pre-fusion F protein stimulated high titers of neutralizing antibodies (NA) while an immunization with post-F containing VLPs or a second RSV infection only weakly stimulated NA even though total anti-F protein IgG antibody levels in both VLP immunized animals were similar...
February 13, 2019: Journal of Virology
Christopher M Goodwin, Joshua Munger
Human Cytomegalovirus (HCMV) is a ubiquitous herpesvirus that causes disease in immunosuppressed populations. HCMV has a complex relationship with innate immune signaling pathways. Specifically, HCMV has been found to block some aspects of inflammatory signaling while benefiting from others. Through analysis of knockout cell lines targeting the NFκB regulatory kinases IKKα and IKKβ, we find that the IKK kinases are host restriction factors that contribute to cytokine-mediated resistance to viral infection, limit the initiation of HCMV infection, and attenuate viral cell-to-cell spread...
February 13, 2019: Journal of Virology
Megan A Hahn, Nolwenn M Dheilly
The complete genome sequence of an RNA virus was assembled from RNA sequencing of virus particles purified from threespine stickleback intestine tissue samples. This new virus is most closely related to the Eel Picornavirus and can be assigned to the genus Potamipivirus in the family Picornaviridae Its unique genetic properties are enough to establish a new species, dubbed the Threespine Stickleback Picornavirus (TSPV). Due to their broad geographic distribution throughout the northern hemisphere and parallel adaptation to freshwater, threespine sticklebacks have become a model in evolutionary ecology...
February 13, 2019: Journal of Virology
Edwige Berthelot, Marie Ducousso, Jean-Luc Macia, Florent Bogaert, Volker Baecker, Gaël Thébaud, Romain Gallet, Michel Yvon, Stéphane Blanc, Mounia Khelifa, Martin Drucker
Cauliflower mosaic virus (CaMV, family Caulimoviridae ) responds to the presence of aphid vectors on infected plants by forming specific transmission morphs. This phenomenon, coined transmission activation (TA), controls plant-to-plant propagation of CaMV. A fundamental question is whether other viruses rely on TA. Here, we demonstrate that transmission of the unrelated Turnip mosaic virus (TuMV, family Potyviridae ) is activated by the reactive oxygen species H2 O2 and inhibited by the calcium channel blocker LaCl3 H2 O2 -triggered TA manifested itself by the induction of intermolecular cysteine bonds between viral HC-Pro molecules and by formation of viral transmission complexes, composed of TuMV particles and HC-Pro that mediates vector-binding...
February 13, 2019: Journal of Virology
Maliheh Safari, Matthew J Ferrari, Marilyn J Roossinck
Plants are frequently infected with cytoplasmic RNA viruses that persist for many generations through nearly 100% vertical transmission without producing any symptoms. Movement between plant cells and horizontal transmission has not been observed in these viruses; instead they are distributed to all host cells through host cell division. Jalapeño peppers ( Capsicum annuum ) are all infected with Pepper cryptic virus 1 (PCV 1, family Partitiviridae ). We compared the effect of odor cues from PCV 1 infected (J+) and virus free (J-) Jalapeño pepper on the aphid Myzus periscae , a common vector of acute plant viruses...
February 13, 2019: Journal of Virology
Audra J Charron, Stephen L Ward, Brian J North, Stacey Ceron, David A Leib
Herpes simplex virus type 1 (HSV-1) cycles between phases of latency in sensory neurons and replication in mucosal sites. HSV-1 encodes two key proteins that antagonize the shutdown of host translation; US11 through preventing PKR activation, and ICP34.5 through mediating eIF2α dephosphorylation. While the profound attenuation of ICP34.5 deletion mutants has been repeatedly demonstrated, a role for US11 in HSV-1 pathogenesis remains unclear. We therefore generated an HSV-1 strain 17 US11 null virus and examined its properties in vitro and in vivo In U373 glioblastoma cells, US11 cooperated with ICP34...
February 13, 2019: Journal of Virology
Michiel T van Diepen, Rosamund Chapman, Nicola Douglass, Shireen Galant, Penny L Moore, Emmanuel Margolin, Phindile Ximba, Lynn Morris, Edward P Rybicki, Anna-Lise Williamson
A vaccine regimen that elicits broadly neutralizing antibodies (bNAbs) is a major goal in HIV-1 vaccine research. Here we assessed the immunogenicity of the CAP256SU envelope protein delivered by modified vaccinia virus Ankara (M) and DNA (D) vaccines in different prime/boost combinations followed by a soluble protein (P) boost. The envelope protein (Env) contained a flexible, glycine linker and I559P mutation. Trimer-specific bNAbs PGT145, PG16 and CAP256 VRC26_08 efficiently bound to the membrane-bound CAP256 envelope expressed on the surface of cells transfected or infected with the DNA and MVA vaccines respectively...
February 13, 2019: Journal of Virology
Xu Yang, Jianxun Qi, Ruchao Peng, Lianpan Dai, Ernest A Gould, George F Gao, Po Tien
Tick-borne encephalitis virus (TBEV) and louping ill virus (LIV) are members of the tick-borne flaviviruses (TBFVs) in the family Flaviviridae , which cause encephalomeningitis and encephalitis in humans and other animals. Although vaccines against TBEV and LIV are available, infection rates are rising due to the low vaccination coverage. To date, no specific therapeutics have been licensed. Several neutralizing monoclonal antibodies (MAbs) show promising effectiveness in the control of TBFVs, but the underlying molecular mechanisms are yet to be characterized...
February 13, 2019: Journal of Virology
Christopher D Bowen, Henrik Paavilainen, Daniel W Renner, Jussi Palomäki, Jenni Lehtinen, Tytti Vuorinen, Peter Norberg, Veijo Hukkanen, Moriah L Szpara
A majority of adults in Finland are seropositive carriers of herpes simplex viruses (HSV). Infection occurs at epithelial or mucosal surfaces, after which virions enter innervating nerve endings, eventually establishing lifelong infection in neurons of the sensory or autonomic nervous system. Recent data have highlighted the genetic diversity of HSV-1 strains, and demonstrated apparent geographic patterns in strain similarity. Though multiple HSV-1 genomes have been sequenced from Europe to date, there is a lack of sequenced genomes from Nordic countries...
February 13, 2019: Journal of Virology
GuanQun Liu, Yan Zhou
Innate immune sensing of influenza A virus (IAV) requires RIG-I, a fundamental cytoplasmic RNA sensor. How RIG-I's cytoplasmic localization reconciles with the nuclear replication nature of IAV is poorly understood. Recent findings provide advanced insights into the spatiotemporal RIG-I sensing of IAV and highlight the contribution of various RNA ligands to RIG-I activation. Understanding a compartment-specific RIG-I sensing paradigm would facilitate the identification of the full spectrum of physiological RIG-I ligands produced during IAV infection...
February 13, 2019: Journal of Virology
Mingkui Zhou, Michael Humbert, Muhammad M Mukhtar, Hanna B Scinto, Hemant K Vyas, Samir K Lakhashe, Siddappa N Byrareddy, Gregor Maurer, Swati Thorat, Joshua Owuor, Zhao Lai, Yidong Chen, Anthony Griffiths, Agnès-Laurence Chenine, Sanjeev Gumber, François Villinger, David Montefiori, Ruth M Ruprecht
Simian-human immunodeficiency virus (SHIV) infection in rhesus macaques (RMs) resembles human immunodeficiency virus type 1 (HIV-1) infection in humans and serves as a tool to evaluate candidate AIDS vaccines. HIV-1 clade A (HIV-A) predominates in parts of Africa. We constructed an R5 clade A SHIV (SHIV-A; strain SHIV-KNH1144) carrying env from a Kenyan HIV-A. SHIV-A underwent rapid serial passage through six RMs. To allow unbridled replication without adaptive immunity, we simultaneously ablated CD8+ and B cells with cytotoxic monoclonal antibodies in the next RM, resulting in extremely high viremia and CD4+ T-cell loss...
February 13, 2019: Journal of Virology
Fujun Qin, Congrui Xu, Jia Hu, Chengfeng Lei, Zhenhua Zheng, Ke Peng, Hanzhong Wang, Xiulian Sun
The budded virus of Autographa californica multiple nucleopolyhedrovirus (AcMNPV) infects insect cells through mainly clathrin-mediated endocytosis. However, the cell entry pathway of AcMNPV remains unclear. In this study, by using population-based analysis of single-virus tracking and electron microscopy, we investigated the internalization, fusion behavior and endocytic trafficking of AcMNPV. AcMNPV internalization into host insect cells was facilitated by actin polymerization and dynamin. After incorporation into early endosomes, AcMNPV envelope fused with the membranes of early endosome, allowing for nucleocapsid release into the cytoplasm...
February 13, 2019: Journal of Virology
Aliza Borenstein-Katz, Anastasiya Shulman, Hedva Hamawi, Orith Leitner, Ron Diskin
There are two predominant subgroups in the Arenaviridae family of viruses, the Old-World and the New-World viruses that use distinct cellular receptors for entry. While New-World viruses typically elicit good neutralizing antibody responses, the Old-World viruses generally evade such responses. Antibody based immune responses are directed against the glycoprotein spike complexes that decorate the viruses. A thick coat of glycans reduces the accessibility of antibodies to the surface of spike complexes from Old-World viruses but other mechanisms may further hamper the development of efficient humoral responses...
February 6, 2019: Journal of Virology
Sung-Chan Wei, Chih-Hsuan Tsai, Wei-Ting Hsu, Yu-Chan Chao
Upon virus infection of a cell, the uncoated DNA is usually blocked by the host intrinsic immune system inside the nucleus. Although it is crucial for the virus to counteract the host intrinsic immune system and access its genome, little is known about how viruses can knock down host restriction and identify their blocked genomes for later viral gene activation and replication. We found that upon baculovirus transduction into Vero E6 cells, the invading viral DNA is trapped by the cellular death domain-associated protein (Daxx) and histone H3...
February 6, 2019: Journal of Virology
Eric J Darrah, Christopher N Jondle, Kaitlin E Johnson, Gang Xin, Philip T Lange, Weiguo Cui, Horatiu Olteanu, Vera L Tarakanova
Gammaherpesviruses are ubiquitous pathogens that are associated with B cell lymphomas. In the early stages of chronic infection these viruses infect naïve B cells and subsequently usurp the B cell differentiation process through the germinal center response to ensure latent infection of long-lived memory B cells. A unique feature of early gammaherpesvirus chronic infection is a robust differentiation of irrelevant, virus-nonspecific B cells with reactivities against self and other species' antigens. In contrast, protective, virus-specific humoral responses do not reach peak levels until a much later time...
February 6, 2019: Journal of Virology
Brenda L Tesini, Preshetha Kanagaiah, Jiong Wang, Megan Hahn, Jessica L Halliley, Francisco A Chaves, Phuong Q T Nguyen, Aitor Nogales, Marta L DeDiego, Christopher S Anderson, Ali H Ellebedy, Shirin Strohmeier, Florian Krammer, Hongmei Yang, Sanjukta Bandyopadhyay, Rafi Ahmed, John J Treanor, Luis Martinez-Sobrido, Hana Golding, Surender Khurana, Martin S Zand, David J Topham, Mark Y Sangster
Memory B cells (MBCs) are key determinants of the B cell response to influenza virus infection and vaccination, but the effect of different forms of influenza antigen exposure on MBC populations has received little attention. We analyzed peripheral blood mononuclear cells and plasma collected following human H3N2 influenza infection to investigate the relationship between hemagglutinin-specific antibody production and changes in the size and character of hemagglutinin-reactive MBC populations. Infection produced increased concentrations of plasma IgG reactive to the H3 head of the infecting virus, to the conserved stalk, and to a broad chronological range of H3s consistent with original antigenic sin responses...
February 6, 2019: Journal of Virology
Satoshi Komoto, Saori Fukuda, Masanori Kugita, Riona Hatazawa, Chitose Koyama, Kazuhiko Katayama, Takayuki Murata, Koki Taniguchi
The generation of recombinant group A rotaviruses (RVAs) entirely from cloned cDNAs has been described only for a single animal RVA strain, simian SA11-L2. We recently developed an optimized RVA reverse genetics system based on only RVA cDNAs (11-plasmid system), in which the concentration of cDNA plasmids containing the NSP2 and NSP5 genes is 3- or 5-fold increased in relation to that of the other plasmids. Based on this approach, we generated a recombinant human RVA (HuRVA)-based monoreassortant virus containing the VP4 gene of the simian SA11-L2 virus using the 11-plasmid system...
February 6, 2019: Journal of Virology
Wenzhong Wei, Joshua Wiggins, Duoyi Hu, Vladimir Vrbanac, Dane Bowder, Michael Mellon, Andrew Tager, Joseph Sodroski, Shi-Hua Xiang
Lactobacillus bacteria are potential delivery vehicles for biopharmaceutical molecules because they are well-recognized as safe microorganisms that naturally inhabit the human body. The goal of this study is to employ these lactobacilli to combat human immunodeficiency virus (HIV-1) infection and transmission. By using a chromosomal integration method, we engineered the Lactobacillus helveticus R0052 strain to display human CD4, the HIV-1 receptor, on the cell surface. Since human CD4 can bind to any infectious HIV-1 particles, the engineered lactobacilli can potentially capture HIV-1 of different sub-types and prevent infection...
February 6, 2019: Journal of Virology
Lauren Williamson, Andrew I Flyak, Nurgun Kose, Robin Bombardi, Andre Branchizio, Srikar Reddy, Edgar Davidson, Benjamin Doranz, Marnie L Fusco, Erica Ollmann Saphire, Peter J Halfmann, Yoshihiro Kawaoka, Ashley E Piper, Pamela J Glass, James E Crowe
The human B cell response to natural filovirus infections early after recovery is poorly understood. Previous serologic studies suggest that some Ebola virus survivors exhibit delayed antibody responses with low magnitude and quality. Here, we sought to study the population of individual memory B cells induced early in convalescence. We isolated monoclonal antibodies (mAbs) from memory B cells from four survivors treated for Ebola virus disease (EVD) one or three-months after discharge from hospital. At the early time points post-recovery, the frequency of Ebola-specific B cells was low and dominated by clones that were cross-reactive with both Ebola glycoprotein (GP) and with the secreted form (sGP)...
February 6, 2019: Journal of Virology
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