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Journal of Virology

Yonggang Pei, Rajnish Kumar Singh, Sanket Kumar Shukla, Fengchao Lang, Shengwei Zhang, Erle S Robertson
Cell cycle regulation is one of the hallmarks of virus-mediated oncogenesis. EBV-induced lymphomas express a repertoire of essential viral latent proteins that regulate expression of cell cycle-related proteins to dysregulate this process thereby facilitating the proliferation of infected cells. We now demonstrate that the essential EBV latent protein 3C (EBNA3C) stabilizes Cyclin D2 to regulate cell cycle progression. More specifically, EBNA3C directly binds to Cyclin D2, and co-localizes together in nuclear compartments...
July 11, 2018: Journal of Virology
Deng Pan, Tian Han, Shubing Tang, Wenjia Xu, Qunchao Bao, Yamei Sun, Baoqin Xuan, Zhikang Qian
Viral gene expression is tightly regulated during cytomegalovirus (CMV) lytic replication, but the detailed mechanism of late gene transcription remains to be fully understood. Previous studies reported that six viral proteins (named viral transactivation factors, [vTFs]) supporting late gene expression were conserved in β- and γ-herpesviruses, but not in α-herpesviruses. Here, we performed coimmunopreciptation experiments to elucidate the organization of these six proteins in murine CMV. Our results showed that these proteins formed a complex by both direct and indirect interactions...
July 11, 2018: Journal of Virology
Maud Mavigner, Jakob Habib, Claire Deleage, Elias Rosen, Cameron Mattingly, Katherine Bricker, Angela Kashuba, Franck Amblard, Raymond F Schinazi, Sherrie Jean, Joyce Cohen, Colleen McGary, Mirko Paiardini, Matthew P Wood, Donald L Sodora, Guido Silvestri, Jacob Estes, Ann Chahroudi
Worldwide, nearly two million children are infected with HIV, with breastfeeding accounting for the majority of contemporary HIV transmissions. Antiretroviral therapy (ART) has reduced HIV-related morbidity and mortality but is not curative. The main barrier to a cure is persistence of latent HIV in long-lived reservoirs. However, our understanding of the cellular and anatomic sources of the HIV reservoir during infancy and childhood is limited. Here, we developed a pediatric model of ART suppression in orally SIV-infected rhesus macaque (RM) infants, with measurement of virus persistence in blood and tissues after 6-9 months of ART...
July 11, 2018: Journal of Virology
Tetsuro Komatsu, Charlotte Quentin-Froignant, Irene Carlon-Andres, Floriane Lagadec, Fabienne Rayne, Jessica Ragues, Ralph H Kehlenbach, Wenli Zhang, Anja Ehrhardt, Kerstin Bystricky, Renaud Morin, Jean-Michel Lagarde, Franck Gallardo, Harald Wodrich
Adenoviruses are DNA viruses with a lytic infection cycle. Following the fate of incoming as well as recently replicated genomes during infections is a challenge. In this study we used a bacterial partitioning system based on the Anch OR3 technology to establish a versatile in vivo imaging system for adenoviral genomes. This system allows the visualization of both individual incoming and newly replicated genomes in real time in living cells. We demonstrate that incoming adenoviral genomes are attached to condensed cellular chromatin during mitosis, facilitating the equal distribution of viral genomes in daughter cells after cell division...
July 11, 2018: Journal of Virology
Kun-Wei Chan, Ruimin Pan, Matthew Costa, Miroslaw K Gorny, Shixia Wang, Shan Lu, Xiang-Peng Kong
Elucidating the structural basis of antibody (Ab) gene usage and affinity maturation of vaccine-induced Abs can inform the design of immunogens for inducing desired Ab responses in HIV vaccine development. Analyses of monoclonal Abs (mAbs) encoded by the same immunoglobulin genes in different stages of maturation can help to understand the maturation process. We have analyzed four human anti-V3 mAbs with the same VH1-3*01 and VL3-10*01 gene usage. Two mAbs, TA6 and TA7, were developed from a vaccinee in the HIV vaccine phase I trial DP6-001 with a polyvalent DNA prime - protein boost regimen, and two others, 311-11D and 1334, were developed from HIV-infected patients...
July 11, 2018: Journal of Virology
Amr Aswad, Aris Katzourakis
Like many other large dsDNA viruses, herpesviruses are known to capture host genes to evade host defenses. Little is known about the detailed natural history of such genes, nor do we fully understand their evolutionary dynamics. A major obstacle is that they are often highly divergent, maintaining very low sequence similarity to host homologs. Here, we use the herpesvirus genus Rhadinovirus as a model system to develop an analytical approach that combines complementary evolutionary and bioinformatic techniques, offering results that are both detailed and robust for a range of genes...
July 11, 2018: Journal of Virology
Ross W Walton, Michael C Brown, Matthew T Sacco, Matthias Gromeier
We are pursuing cancer immunotherapy with neuro-attenuated recombinant poliovirus, PVSRIPO. PVSRIPO is the live attenuated type 1 (Sabin) poliovirus vaccine carrying a heterologous internal ribosomal entry site (IRES) of human rhinovirus type 2 (HRV2). Intratumoral infusion of PVSRIPO is showing promise in the therapy of recurrent WHO grade IV malignant glioma (glioblastoma), a notoriously treatment-refractory cancer with dismal prognosis. PVSRIPO exhibits profound cytotoxicity in infected neoplastic cells expressing the poliovirus receptor CD155...
July 11, 2018: Journal of Virology
Cindy Buffone, Alicia Martinez-Lopez, Thomas Fricke, Silvana Opp, Marco Severgnini, Ingrid Cifola, Luca Petiti, Stella Frabetti, Katarzyna Skorupka, Kaneil K Zadrozny, Barbie K Ganser-Pornillos, Owen Pornillos, Francesca Di Nunzio, Felipe Diaz-Griffero
HIV-1 displays the unique ability to infect non-dividing cells. The capsid of HIV-1 is the viral determinant for viral nuclear import. To understand the cellular factors involved in the ability of HIV-1 to infect non-dividing cells, we sought to find capsid mutations that allow the virus to infect dividing but not non-dividing cells. Because the interaction of capsid with the nucleoporin protein 153 (Nup153) is important for nuclear import of HIV-1, we solved new crystal structures of hexameric HIV-1 capsid in complex with a Nup153-derived peptide containing a phenylalanine-glycine repeat (FG-repeat), which we used to guide structure-based mutagenesis of the capsid-binding interface...
July 11, 2018: Journal of Virology
Hui Yuan, Jia You, Hongjuan You, Chunfu Zheng
Type I interferons (IFNs), as major components of the innate immune system, play a vital role in host resistance to a variety of pathogens. Canonical signaling mediated by type I IFNs activates the Janus kinase-signal transducer and activator of transcription (JAK-STAT) pathway through binding to IFN-α/β receptor (IFNAR), resulting in transcription of IFN-stimulated genes (ISGs). However, viruses have evolved multiple strategies to evade this process. Here, we report that herpes simplex virus 1 (HSV-1) ubiquitin-specific protease (UL36USP) abrogates type I IFN-mediated signaling pathway independent of its deubiquitinase (DUB) activity...
July 11, 2018: Journal of Virology
Doty B A Ojwach, Daniel MacMillan, Tarylee Reddy, Vladimir Novitsky, Zabrina L Brumme, Mark A Brockman, Thumbi Ndung'u, Jaclyn K Mann
CD8+ T cell mediated escape mutations in Gag can reduce HIV-1 replication capacity (RC) and alter disease progression, but less is known about immune-mediated attenuation in other HIV-1 proteins. We generated 487 recombinant viruses encoding RT-integrase from individuals with chronic (n = 406) and recent (n = 81) HIV-1 subtype C infection and measured their in vitro RC using a GFP-reporter T-cell assay. In recently-infected individuals, RT-integrase driven RC correlated significantly with viral load set point ( r = 0...
July 11, 2018: Journal of Virology
Ninad Mehta, Emeka K Enwere, Theodore Dos Santos, Holly A Saffran, Bart Hazes, David Evans, Michele Barry, James R Smiley
Poxviruses encode many proteins with the ability to regulate cellular signaling pathways. One such protein is the vaccinia virus innate immunity modulator E3. Multiple functions have been ascribed to E3, including modulating the cellular response to double stranded RNA, inhibiting the NF-κB and IRF3 pathways, and dampening apoptosis. Apoptosis serves as a powerful defense against damaged and unwanted cells and is an effective defense against viral infection; many viruses therefore encode proteins that prevent or delay apoptosis...
July 11, 2018: Journal of Virology
Christopher C Nguyen, Mohammed N A Siddiquey, Hongbo Zhang, Gang Li, Jeremy P Kamil
UL148 is a viral endoplasmic reticulum (ER)-resident glycoprotein that contributes to human cytomegalovirus (HCMV) cell tropism. The influence of UL148 on tropism correlates with its potential to promote the expression of glycoprotein O (gO), a viral envelope glycoprotein that participates in a heterotrimeric complex with glycoproteins H and L that is required for infectivity. In an effort to gain insight into mechanism, we used mass spectrometry to identify proteins that co-immunoprecipitate from infected cells with UL148...
July 11, 2018: Journal of Virology
Feng Wen, Sherry Blackmon, Alicia K Olivier, Lei Li, Minhui Guan, Hailiang Sun, Peng George Wang, Xiu-Feng Wan
An outbreak of respiratory disease caused by the equine-origin influenza A(H3N8) virus was first detected in dogs in 2004 and since then, has been enzootic among dogs. Currently, the molecular mechanisms underlying host adaption of this virus from horses to dogs is unknown. Here, we have applied quantitative binding, growth kinetics, and immunofluorescence analyses to elucidate these mechanisms. Our findings suggest that a substituation of W222L in the hemagglutinin of the equine-origin A(H3N8) virus facilitated its host adaption to dogs...
July 11, 2018: Journal of Virology
He Huang, Chongyang Zhang, Bei Wang, Fei Wang, Bin Pei, Chaofei Cheng, Wei Yang, Zhendong Zhao
RNA interference (RNAi) is widely used in gene-knockdown analysis and as a tool to screen host genes involved in viral infection. Owing to the limitations of transducing cells with synthetic small interfering RNAs (siRNA), lentiviral short-hairpin RNA (shRNA) vectors are more widely used. However, we found that stable transduction with lentiviral shRNA vectors inhibited hepatitis C virus (HCV) propagation in human hepatoma cells. We found by miRNA microarray analysis that this inhibition was induced by the alteration of host microRNA (miRNA) expression...
July 11, 2018: Journal of Virology
Michael Herren, Neeta Shrestha, Marianne Wyss, Andreas Zurbriggen, Philippe Plattet
Morbilliviruses ( e.g Measles virus (MeV) or Canine Distemper Virus (CDV)) host cell entry is coordinated by two interacting envelope glycoproteins; namely, an attachment (H) protein and a fusion (F) protein. The ectodomain of H-proteins consists of stalk, connector and head domains that assemble into functional non-covalent dimer-of-dimers. The role of the C-terminal module of the H-stalk domain (termed "linker") and the connector, although putatively able to assume flexible structures and allow receptor-induced structural rearrangements, remains largely unexplored...
July 11, 2018: Journal of Virology
Jordan Ari Schwartz, Hongliang Zhang, Zachary Ende, Martin J Deymier, Terry Lee, Joel Singer, Tony Mazzulli, Eric Hunter, Mario A Ostrowski
HIV-1 infection often arises from a single transmitted/founder (TF) viral variant, amongst a large pool of viruses in the quasispecies in the transmitting partner. TF variants are typically non-dominant in blood and genital secretions, indicating unique traits. The plasmacytoid dendritic cell (pDC) is the primary IFN-α producing cell in response to viral infections, and is rapidly recruited to the female genital tract upon exposure to HIV-1. The impact of the pDC on transmission is unknown. We investigated whether evasion of pDC responses was a trait of TF viruses...
July 11, 2018: Journal of Virology
Hsin Chien, Christine I Alston, Richard D Dix
AIDS-related human cytomegalovirus retinitis remains the leading cause of blindness among untreated HIV/AIDS patients worldwide. To study mechanisms of this disease, we use a clinically relevant animal model of murine cytomegalovirus (MCMV) retinitis with retrovirus-induced murine acquired immunodeficiency syndrome (MAIDS) that mimics the progression of AIDS in humans. We found in this model that MCMV infection significantly stimulates ocular suppressor of cytokine signaling (SOCS)1 and SOCS3, host proteins which hinder immune-related signaling by cytokines, including antiviral type I and type II interferons...
July 5, 2018: Journal of Virology
Julia C Frei, Ariel S Wirchnianski, Jennifer Govero, Olivia Vergnolle, Kimberly A Dowd, Theodore C Pierson, Margaret Kielian, Mark E Girvin, Michael S Diamond, Jonathan R Lai
Dengue virus is the most globally prevalent mosquito-transmitted virus. Primary infection with one of four co-circulating serotypes (DENV1-4) causes a febrile illness but secondary infection with a heterologous serotype can result in severe disease due in part to antibody dependent enhancement of infection (ADE). In ADE, cross-reactive but non-neutralizing antibodies, or sub-protective levels of neutralizing antibodies, promote uptake of antibody-opsonized virus in Fc-γ receptor-positive cells. Thus, elicitation of broadly neutralizing antibodies (bNAbs), but not non-neutralizing antibodies, is desirable for Dengue vaccine development...
July 5, 2018: Journal of Virology
Matthew T Chambers, Megan C Schwarz, Marion Sourisseau, Essanna S Gray, Matthew J Evans
Zika virus (ZIKV) glycoproteins are the primary target of the humoral immune response. In this study, we explored the capacity of these glycoproteins to tolerate insertion of linear epitope sequences, and the potential of antibodies that bind these epitopes to inhibit infection. We first created a panel of ZIKV mutants with the FLAG epitope inserted in premembrane (prM) and envelope (E) glycoprotein regions. Insertion locations were based on the results of our recent transposon insertional mutagenesis screen...
July 5, 2018: Journal of Virology
Salar N Khan, Devin Sok, Karen Tran, Arlette Movsesyan, Viktoriya Dubrovskaya, Dennis Burton, Richard T Wyatt
Protection against acquiring HIV infection may not require a vaccine in the conventional sense, because broadly neutralizing antibodies (bNAbs) alone prevent HIV infection in relevant animal challenge models. Additionally, bNAbs as therapeutics can effectively suppress HIV replication in infected humans and in animal models. Combinations of bNAbs are generally even more effective and bNAb-derived multivalent antibody-like molecules also inhibit HIV replication both in vitro and in vivo. To expand the available array of multi-specific HIV inhibitors, we designed single-component molecules that incorporate two (bispecific) or three (trispecific) bNAbs that recognize HIV Env exclusively, a bispecific CrossMab targeting two epitopes on the major HIV co-receptor, CCR5, and bi- and trispecifics that cross-target both Env and CCR5...
July 5, 2018: Journal of Virology
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