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Journal of Virology

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https://www.readbyqxmd.com/read/29142137/the-epstein-barr-virus-episome-maneuvers-between-nuclear-chromatin-compartments-during-reactivation
#1
Stephanie A Moquin, Sean Thomas, Sean Whalen, Alix Warburton, Samantha G Fernandez, Alison A McBride, Katherine S Pollard, J J L Miranda
The human genome is structurally organized in three-dimensional space to facilitate functional partitioning of transcription. We learned that the latent episome of the human Epstein-Barr virus (EBV) preferentially associates with gene-poor chromosomes and avoids gene-rich chromosomes. Kaposi's sarcoma-associated herpesvirus behaves similarly, but human papillomavirus does not. Contacts localize on the EBV side to OriP, the latent origin of replication. This genetic element, and the EBNA1 protein that binds there, are sufficient to reconstitute chromosome association preferences of the entire episome...
November 15, 2017: Journal of Virology
https://www.readbyqxmd.com/read/29142136/size-composition-and-evolution-of-hiv-dna-populations-during-early-antiretroviral-therapy-and-intensification-with-maraviroc
#2
Antoine Chaillon, Sara Gianella, Steven M Lada, Josué Perez-Santiago, Parris Jordan, Caroline Ignacio, Maile Karris, Douglas Richman, Sanjay R Mehta, Susan J Little, Joel O Wertheim, Davey M Smith
Residual viremia is common during antiretroviral therapy (ART), and could be caused by ongoing low-level virus replication or by release of viral particles from infected cells. ART Intensification should impact ongoing viral propagation but not virion release. Eighteen acutely infected men were enrolled in a randomized controlled trial, and followed for a median of 107 weeks. Participants started ART with (n=9) or without (n=9) intensification with maraviroc (MVC) within 90 days of infection. Levels of HIV DNA and cell-free RNA were quantified by droplet digital PCR...
November 15, 2017: Journal of Virology
https://www.readbyqxmd.com/read/29142135/autographa-californica-nucleopolyhedrovirus-ac141-exon0-a-potential-e3-ubiquitin-ligase-interacts-with-viral-ubiquitin-and-ac66-to-facilitate-nucleocapsid-egress
#3
Siddhartha Biswas, Leslie G Willis, Minggang Fang, Yingchao Nie, David A Theilmann
During the infection cycle of Autographa californica multiple nucleopolyhedrovirus (AcMNPV) two forms of virions are produced, budded virus (BV) and occlusion derived virus (ODV). Nucleocapsids that form BV have to egress from the nucleus whereas nucleocapsids that form ODVs remain inside the nucleus. The molecular mechanism that determines whether nucleocapsids remain inside or egress from the nucleus is unknown. AC141 (a predicted E3 ubiquitin ligase) and viral ubiquitin (vUbi) have both been shown to be required for efficient BV production...
November 15, 2017: Journal of Virology
https://www.readbyqxmd.com/read/29142134/tnf-mediated-survival-of-cd169-cells-promotes-immune-activation-during-vesicular-stomatitis-virus-infection
#4
Prashant V Shinde, Haifeng C Xu, Sathish Kumar Maney, Andreas Kloetgen, Sukumar Namineni, Yuan Zhuang, Nadine Honke, Namir Shaabani, Nicolas Bellora, Mareike Doerrenberg, Mirko Trilling, Vitaly I Pozdeev, Nico van Rooijen, Stefanie Scheu, Klaus Pfeffer, Paul R Crocker, Masato Tanaka, Sujitha Duggimpudi, Percy Knolle, Mathias Heikenwalder, Jürgen Ruland, Tak W Mak, Dirk Brenner, Aleksandra A Pandyra, Jessica I Hoell, Arndt Borkhardt, Dieter Häussinger, Karl S Lang, Philipp A Lang
Innate immune activation is essential to mount an effective antiviral response and to prime adaptive immunity. Although a crucial role of CD169(+) cells during vesicular stomatitis virus (VSV) infections is increasingly recognized, factors regulating CD169(+) cells during viral infections remain unclear. Here we show that tumor necrosis factor is produced by CD11b(+) Ly6C(+)Ly6G(+) cells following infection with VSV. The absence of TNF or TNF receptor 1 (TNFR1) resulted in reduced numbers of CD169(+) cells and in reduced IFN-I production during VSV infection, with a severe disease outcome...
November 15, 2017: Journal of Virology
https://www.readbyqxmd.com/read/29142133/human-adenovirus-infection-causes-the-cellular-mkrn1-e3-ubiquitin-ligase-degradation-involving-the-viral-core-protein-pvii
#5
Raviteja Inturi, Kwangchol Mun, Katrin Singethan, Sabrina Schreiner, Tanel Punga
Human adenoviruses (HAdVs) are common human pathogens encoding a highly abundant histone-like core protein VII, which is involved in nuclear delivery and protection of viral DNA as well as in sequestering immune danger signals in infected cells. The molecular details of how protein VII acts as a multifunctional protein have remained to a large extent enigmatic. Here we report the identification of several cellular proteins interacting with the precursor pVII protein. We show that the cellular E3 ubiquitin ligase MKRN1 is a novel precursor pVII interacting protein in HAdV-C5-infected cells...
November 15, 2017: Journal of Virology
https://www.readbyqxmd.com/read/29142132/identification-of-a-small-molecule-that-compromises-the-structural-integrity-of-viroplasms-and-rotavirus-double-layered-particles
#6
Catherine Eichwald, Giuditta De Lorenzo, Elisabeth M Schraner, Guido Papa, Michela Bollati, Paolo Swuec, Matteo de Rosa, Mario Milani, Eloise Mastrangelo, Mathias Ackermann, Oscar R Burrone, Francesca Arnoldi
Despite the availability of two attenuated vaccines, rotavirus (RV) gastroenteritis remains an important cause of mortality among children in developing countries causing about 215,000 infant deaths annually. Currently, there are no specific antiviral therapies available. RV is a non-enveloped virus with a segmented double-stranded RNA genome. Viral genome replication and assembly of transcriptionally active double-layered particles (DLPs) take place in cytoplasmic viral structures called viroplasms. In this study, we describe strong impairment of the early stages of RV replication induced by a small molecule known as RNA polymerase III inhibitor, ML-60218 (ML)...
November 15, 2017: Journal of Virology
https://www.readbyqxmd.com/read/29142131/single-dose-trivalent-vesiculovax-vaccine-protects-macaques-from-lethal-ebolavirus-and-marburgvirus-challenge
#7
Demetrius Matassov, Chad E Mire, Theresa Latham, Joan B Geisbert, Rong Xu, Ayuko Ota-Setlik, Krystle N Agans, Dean J Kobs, Morgan Q S Wendling, Amanda Burnaugh, Thomas L Rudge, Carol L Sabourin, Michael A Egan, David K Clarke, Thomas W Geisbert, John H Eldridge
Previous studies demonstrated that a single intramuscular (IM) dose of an attenuated vesicular stomatitis virus vector (Vesiculovax™, rVSV-N4CT1) expressing the glycoprotein (GP) from the Mayinga strain of Zaire ebolavirus (EBOV) protected nonhuman primates (NHP) from lethal challenge with EBOV Kikwit and Makona strains. Here we studied the immunogenicity of an expanded range of attenuated rVSV vectors expressing filovirus GP in mice. Based on data from those studies an optimal attenuated tri-valent rVSV vector formulation was identified which included rVSV vectors expressing EBOV, Sudan ebolavirus (SUDV) or Angola strain of Marburg marburgvirus (MARV) GPs...
November 15, 2017: Journal of Virology
https://www.readbyqxmd.com/read/29142130/effective-priming-of-hsv-specific-cd8-t-cells-in-vivo-does-not-require-infected-dendritic-cells
#8
Paul G Whitney, Christina Makhlouf, Beth MacLeod, Joel Z Ma, Elise Gressier, Marie Greyer, Katharina Hochheiser, Annabell Bachem, Ali Zaid, David Voehringer, William R Heath, Mayura V Wagle, Ian Parish, Tiffany A Russell, Stewart A Smith, David C Tscharke, Thomas Gebhardt, Sammy Bedoui
Resolution of virus infections depends on the priming of virus-specific CD8(+) T cells by dendritic cells (DC). While this process requires MHC class I-restricted antigen presentation by DC, the relative contribution to CD8(+) T cell priming by infected DC is less clear. We have addressed this question in the context of a peripheral infection with herpes simplex virus type 1 (HSV). Assessing the endogenous, polyclonal HSV-specific CD8(+) T cell response, we found that effective in vivo T cell priming depended on the presence of DC subsets specialized in cross-presentation while Langerhans cells and plasmacytoid DC were dispensable...
November 15, 2017: Journal of Virology
https://www.readbyqxmd.com/read/29142129/entry-of-human-coronavirus-nl63-to-the-cell
#9
Aleksandra Milewska, Paulina Nowak, Katarzyna Owczarek, Artur Szczepanski, Miroslaw Zarebski, Agnieszka Hoang-Bujnowicz, Krzysztof Berniak, Jacek Wojarski, Slawomir Zeglen, Zbigniew Baster, Zenon Rajfur, Krzysztof Pyrc
First steps of human coronavirus NL63 (HCoV-NL63) infection were previously described. The virus binds to target cells by heparan sulfate proteoglycans, and interacts with the ACE2 protein. Subsequent events, including virus internalization and trafficking, remain to be elucidated. In this study, we mapped the process of HCoV-NL63 entry into LLC-Mk2 cell line and ex vivo 3D tracheobronchial tissue.Using a variety of techniques we have shown that HCoV-NL63 virions require endocytosis for successful entry to the LLC-MK2 cells, and interaction between the virus and the ACE2 molecule triggers recruitment of clathrin...
November 15, 2017: Journal of Virology
https://www.readbyqxmd.com/read/29142128/interaction-between-a-unique-minor-protein-and-a-major-capsid-protein-of-bluetongue-virus-controls-virus-infectivity
#10
Eiko Matsuo, Kiyoshi Yamazaki, Hiroki Tsuruta, Polly Roy
Among the Reoviridae family of double-stranded RNA viruses, only members of the Orbivirus genus possess a unique structural protein, termed VP6, within their particles. Bluetongue virus (BTV), an important livestock pathogen, is the prototype Orbivirus The BTV VP6 is an ATP-dependent RNA helicase and it is indispensable for virus replication. In this report, we investigated how VP6 might be recruited to the virus capsid and whether the BTV structural protein VP3, which forms the internal layer of the virus capsid core, is involved in VP6 recruitment...
November 15, 2017: Journal of Virology
https://www.readbyqxmd.com/read/29142127/epstein-barr-virus-protein-eb2-stimulates-translation-initiation-of-mrnas-through-direct-interactions-with-both-pabp-and-eif4g
#11
Fabrice Mure, Baptiste Panthu, Isabelle Zanella-Cléon, Frédéric Delolme, Evelyne Manet, Théophile Ohlmann, Henri Gruffat
Epstein-Barr virus (EBV) expresses several mRNAs produced from intronless genes that could potentially be unfavorably translated compared to cellular spliced mRNAs. To overcome this situation, the virus encodes an RNA-binding protein (RBP) called EB2, previously found to both facilitate the export of nuclear mRNAs and increase their translational yield. Here, we show that EB2 binds both nuclear and cytoplasmic cap-binding complexes (respectively, CBC and eIF4F) as well as the poly(A)-binding protein (PABP) to enhance translation initiation of a given mRNP...
November 15, 2017: Journal of Virology
https://www.readbyqxmd.com/read/29142126/hpv-replication-regulation-by-acetylation-of-a-conserved-lysine-in-the-e2-protein
#12
Yanique Thomas, Elliot J Androphy
The Papillomavirus (PV) E2 protein is a sequence specific DNA binding protein that recruits cellular factors to its genome in infected epithelial cells. E2 also binds to and loads the viral E1 DNA helicase at the origin of replication. Post-translational modifications (PTMs) of PV E2 have been identified as potential regulators E2 functions. We recently reported lysine (K) 111 as a target of p300 acetylation in bovine (B)PV. The di-lysines at 111 and 112 are conserved in almost all papillomaviruses. We pursued a mutational approach to query the functional significance of lysine in human (H)PV E2...
November 15, 2017: Journal of Virology
https://www.readbyqxmd.com/read/29142125/emergence-of-double-and-triple-gene-reassortant-g1p-8-rotaviruses-possessing-a-ds-1-like-backbone-post-rotavirus-vaccine-introduction-in-malawi
#13
Khuzwayo C Jere, Chrispin Chaguza, Naor Bar-Zeev, Jenna Lowe, Chikondi Peno, Benjamin Kumwenda, Osamu Nakagomi, Jacqueline E Tate, Umesh D Parashar, Robert S Heyderman, Neil French, Nigel A Cunliffe, Iturriza-Gomara Miren
To combat the high burden of rotavirus gastroenteritis, multiple African countries have introduced rotavirus vaccines into their childhood immunisation programmes. Malawi incorporated a G1P[8] rotavirus vaccine (Rotarix™) into its immunisation schedule in 2012. Utilising a surveillance platform of hospitalised rotavirus gastroenteritis cases, we examined the phylodynamics of G1P[8] rotavirus strains that circulated in Malawi before (1998 - 2012) and after (2013 - 2014) vaccine introduction. Analysis of whole genomes obtained through next generation sequencing revealed that all randomly-selected pre-vaccine G1P[8] strains sequenced (n=32) possessed a Wa-like genetic constellation, whereas post-vaccine G1P[8] strains (n=18) had a DS-1-like constellation...
November 15, 2017: Journal of Virology
https://www.readbyqxmd.com/read/29142124/truncating-the-gp41-cytoplasmic-tail-of-siv-decreases-sensitivity-to-neutralizing-antibodies-without-increasing-envelope-content-of-virions
#14
Ellen White, Fan Wu, Elena Chertova, Julian Bess, James D Roser, Jeffrey D Lifson, Vanessa M Hirsch
An incomplete understanding of native HIV and SIV envelope glycoprotein (Env) impedes the development of structural models of Env and vaccine design. This shortcoming is due in part to the low number of Env trimers on virus particles. For SIV, this low expression can be counteracted by truncating the cytoplasmic tail (CT) of Env. CT truncation has been shown to increase Env incorporation into the virion and is commonly used in vaccine and imaging studies, but its effects on viral antigenicity have not been fully elucidated...
November 15, 2017: Journal of Virology
https://www.readbyqxmd.com/read/29142123/initiation-elongation-and-realignment-during-influenza-virus-mrna-synthesis
#15
Aartjan J W Te Velthuis, Judith Oymans
The RNA-dependent RNA polymerase (RdRp) of the influenza A virus replicates and transcribes the viral genome segments in the nucleus of the host cell. To transcribe these viral genome segments, the RdRp 'snatches' capped RNA oligonucleotides from nascent host cell mRNAs and aligns these primers to the ultimate or penultimate nucleotide of the segments for the initiation of viral mRNA synthesis. It has been proposed that this initiation process is not processive and that the RdRp uses a prime-realign mechanism during transcription...
November 15, 2017: Journal of Virology
https://www.readbyqxmd.com/read/29142122/adaptive-immune-responses-following-senecavirus-a-infection-in-pigs
#16
Mayara F Maggioli, Steve Lawson, Marcelo de Lima, Lok R Joshi, Tatiane C Faccin, Fernando V Bauermann, Diego G Diel
Senecavirus A (SVA), an emerging picornavirus of swine, causes vesicular disease (VD) that is clinically indistinguishable from foot-and-mouth disease (FMD) in pigs. Many aspects of SVA interactions with the host and the host immune responses to infection, however, remain unknown. In the present study, humoral and cellular immune responses to SVA were evaluated following infection in pigs. We show that SVA infection elicited an early and robust neutralizing antibody (NA) response, which coincided with and was strongly correlated with VP2- and VP3-specific IgM responses...
November 15, 2017: Journal of Virology
https://www.readbyqxmd.com/read/29118127/peripheral-blood-biomarkers-of-disease-outcome-in-a-monkey-model-of-rift-valley-fever-encephalitis
#17
Elizabeth R Wonderlich, Amy L Caroline, Cynthia M McMillen, Aaron W Walters, Douglas S Reed, Simon M Barratt-Boyes, Amy L Hartman
Rift Valley Fever (RVF) is an emerging arboviral disease of livestock and people. Although a mosquito-borne virus, humans are infected through contact with or inhalation of virus-laden particles from contaminated animal carcasses. Some individuals infected with RVF virus (RVFV) develop meningoencephalitis resulting in morbidity and mortality. Little is known about the pathogenic mechanisms that lead to neurologic sequelae, and thus animal models that represent human disease are needed. African green monkeys (AGM) exposed to aerosols containing RVFV develop a reproducibly lethal neurological disease that resembles human illness...
November 8, 2017: Journal of Virology
https://www.readbyqxmd.com/read/29118126/respiratory-syncytial-virus-rsv-targeting-the-g-protein-provides-a-new-approach-for-an-old-problem
#18
Ralph A Tripp, Ultan F Power, Peter J M Openshaw, Lawrence M Kauvar
Respiratory syncytial virus (RSV) is a major cause of lower respiratory tract infection (LRTI) annually affecting >2 million children in the US <5 years old. In the elderly (>65 years old), RSV results in ∼175,000 hospitalizations annually in the US with worldwide incidence ∼34 million. There is no approved RSV vaccine and treatments are limited. Recently, a Phase 3 trial in the elderly using a recombinant RSV F protein vaccine failed to meet its efficacy objectives, namely prevention of moderate-to-severe RSV-associated LRTI and reduced incidence of acute respiratory disease...
November 8, 2017: Journal of Virology
https://www.readbyqxmd.com/read/29118125/alt-803-transiently-reduces-siv-replication-in-the-absence-of-antiretroviral-treatment
#19
Amy L Ellis-Connell, Alexis J Balgeman, Katie R Zarbock, Gabrielle Barry, Andrea Weiler, Jack O Egan, Emily K Jeng, Thomas Friedrich, Jeffrey S Miller, Ashley T Haase, Timothy W Schacker, Hing C Wong, Eva Rakasz, Shelby L O'Connor
Developing biological interventions to control HIV replication in the absence of antiretroviral therapy (ART) could contribute to the development of a functional cure. As a potential alternative to ART, the IL-15 superagonist ALT-803 has been shown to boost the number and function of HIV-specific CD8(+) T and NK cell populations, in vitro. Four SIV(+) rhesus macaques, three of whom possessed MHC alleles associated with control of SIV, and all of whom had received SIV vaccine vectors that had the potential to elicit CD8(+) T cell responses, were given ALT-803 in three treatment cycles...
November 8, 2017: Journal of Virology
https://www.readbyqxmd.com/read/29118124/c-myc-represses-transcription-of-the-epstein-barr-virus-latent-membrane-protein-1-early-after-primary-b-cell-infection
#20
Alexander M Price, Joshua E Messinger, Micah A Luftig
Recent evidence has shown that the EBV oncogene LMP1 is not expressed at high levels early after EBV-infection of primary B cells, despite its being essential for the long-term outgrowth of immortalized lymphoblastoid cell lines (LCLs). In this study, we found that expression of LMP1 increased fifty-fold between seven days post infection and the LCL state. Metabolic labeling of nascently transcribed mRNA indicated this was primarily a transcription-mediated event. EBNA2, the key viral transcription factor regulating LMP1, and CTCF, an important chromatin insulator, were recruited to the LMP1 locus similarly early and late after infection...
November 8, 2017: Journal of Virology
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