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Journal of Virology

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https://www.readbyqxmd.com/read/28539455/functional-consequences-of-rna-5-terminal-deletions-on-coxsackievirus-b3-rna-replication-and-ribonucleoprotein-complex-formation
#1
Nicolas Lévêque, Magali Garcia, Alexis Bouin, Joseph H C Nguyen, Genevieve P Tran, Laurent Andreoletti, Bert L Semler
Group B coxsackieviruses are responsible for chronic cardiac infections. However, the molecular mechanisms by which the virus can persist in the human heart long after the signs of acute myocarditis have abated are still not completely understood. Recently, coxsackievirus B3 strains with 5' terminal deletions in genomic RNAs were isolated from a patient suffering from idiopathic dilated cardiomyopathy, suggesting that such mutant viruses may be the forms responsible for persistent infection. These deletions lacked portions of 5' stem-loop I, which is an RNA secondary structure required for viral RNA replication...
May 24, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28539454/ebola-virus-delta-peptide-is-a-viroporin
#2
Jing He, Lilia I Melnik, Alexander Komin, Gregory Wiedman, Taylor Fuselier, Cameron F Morris, Charles G Starr, Peter C Searson, William R Gallaher, Kalina Hristova, Robert F Garry, William C Wimley
The Ebola virus (EBOV) genome encodes for a partly conserved, 40-residue, nonstructural polypeptide, called the delta peptide, which is produced in abundance during Ebola virus disease. The function of the delta peptide is unknown, but sequence analysis has suggested that delta peptide could be a viroporin, belonging to a diverse family of membrane-permeabilizing small polypeptides involved in replication and pathogenesis of numerous viruses. Full length and conserved C-terminal delta peptide fragments permeabilize the plasma membranes of nucleated cells of rodent, dog, monkey and human origin, increase ion permeability across confluent cell monolayers and permeabilize synthetic lipid bilayers...
May 24, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28539453/epigenetic-metabolite-acetate-inhibits-class-i-ii-histone-deacetylases-promotes-histone-acetylation-and-increases-hiv-1-integration-in-cd4-t-cells
#3
Jean-François Bolduc, Laurent Hany, Corinne Barat, Michel Ouellet, Michel J Tremblay
In this study, we investigated the effect of acetate, the most concentrated short-chain fatty acid (SCFA) in the gut and bloodstream, on the susceptibility of primary human CD4(+) T cells to HIV-1 infection. We report that HIV-1 replication is increased in CD3/CD28-costimulated CD4(+) T cells upon acetate treatment. This enhancing effect correlates with an increased expression of the early activation marker CD69 and impaired class I/II histone deacetylase (HDAC) activity. In addition, acetate enhances acetylation of histones H3 and H4 and augments HIV-1 integration in the genome of CD4(+) T cells...
May 24, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28539452/interactions-between-hiv-1-gag-and-viral-rna-genome-enhance-virion-assembly
#4
Kari A Dilley, Olga A Nikolaitchik, Andrea Galli, Ryan C Burdick, Louis Levine, Kelvin Li, Alan Rein, Vinay K Pathak, Wei-Shau Hu
Most HIV-1 virions contain two copies of full-length viral RNA, indicating that genome packaging is efficient and tightly regulated. However, the structural protein Gag is the only component required for the assembly of noninfectious virus-like particles and the viral RNA is dispensable in this process. The mechanism that allows HIV-1 to achieve such high efficiency of genome packaging when a packageable viral RNA is not required for virus assembly is currently unknown. In this report, we examined the role of HIV-1 RNA in virus assembly and found that packageable HIV-1 RNA enhances particle production when Gag is expressed at levels similar to those in cells containing one provirus...
May 24, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28539451/reducing-v3-antigenicity-and-immunogenicity-on-soluble-native-like-hiv-1-env-sosip-trimers
#5
Rajesh P Ringe, Gabriel Ozorowski, Kimmo Rantalainen, Weston B Struwe, Katie Matthews, Jonathan L Torres, Anila Yasmeen, Christopher A Cottrell, Thomas J Ketas, Celia C LaBranche, David C Montefiori, Albert Cupo, Max Crispin, Ian A Wilson, Andrew B Ward, Rogier W Sanders, P J Klasse, John P Moore
Native-like trimers of the SOSIP design are being developed as immunogens in human immunodeficiency virus type 1 (HIV-1) vaccine development programs. These trimers display the epitopes for multiple broadly neutralizing antibodies (bNAbs), but can also expose binding sites for some types of non-neutralizing antibodies (non-NAbs). Among the latter are epitopes in the gp120 V3 region that are highly immunogenic when SOSIP trimers are evaluated in animal models. It is presently uncertain whether antibodies against V3 can interfere with the induction of NAbs, but there are good arguments in favor of suppressing such "off-target" immune responses...
May 24, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28539450/mimic-phosphorylation-of-a-%C3%AE-c1-encoded-by-tylccnb-impairs-its-functions-as-a-viral-suppressor-of-rna-silencing-and-a-symptom-determinant
#6
Xueting Zhong, Zhan Qi Wang, Ruyuan Xiao, Linge Cao, Yaqin Wang, Yan Xie, Xueping Zhou
Phosphorylation of the βC1 protein encoded by the betasatellite of tomato yellow leaf curl China virus (TYLCCNB-βC1) by SNF1-related protein kinase 1 (SnRK1) plays a critical role in defense of host plants against geminivirus infection in Nicotiana benthamiana However, how phosphorylation of TYLCCNB-βC1 impacts its pathogenic functions during viral infection remains elusive. In this study, we identified two additional tyrosine residues in TYLCCNB-βC1 that are phosphorylated by SnRK1. The effects of TYLCCNB-βC1 phosphorylation on its functions as a viral suppressor of RNA silencing (VSR) and a symptom determinant were investigated via phosphorylation- mimic mutants in N...
May 24, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28539449/anti-hiv-1-adcc-antibodies-following-latency-reversal-and-treatment-interruption
#7
Wen Shi Lee, Anne B Kristensen, Thomas A Rasmussen, Martin Tolstrup, Lars Østergaard, Ole S Søgaard, Bruce D Wines, P Mark Hogarth, Arnold Reynaldi, Miles P Davenport, Sean Emery, Janaki Amin, David A Cooper, Virginia L Kan, Julie Fox, Henning Gruell, Matthew S Parsons, Stephen J Kent
There is growing interest in utilizing antibody-dependent cellular cytotoxicity (ADCC) to eliminate infected cells following reactivation from HIV-1 latency. A potential barrier is that HIV-1-specific ADCC antibodies decline in patients on long-term antiretroviral therapy (ART) and may not be sufficient to eliminate reactivated latently infected cells. It is not known whether reactivation from latency with latency-reversing agents (LRA) could provide sufficient antigenic stimulus to boost HIV-1-specific ADCC...
May 24, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28539448/virological-control-by-the-cd4-binding-site-antibody-n6-in-shiv-infected-rhesus-monkeys
#8
Boris Julg, Amarendra Pegu, Peter Abbink, Jinyan Liu, Amanda Brinkman, Katherine Molloy, Shanell Mojta, Abishek Chandrashekar, Katherine Callow, Keyun Wang, Xuejun Chen, Stephen D Schmidt, Jinghe Huang, Richard A Koup, Michael S Seaman, Brandon F Keele, John R Mascola, Mark Connors, Dan H Barouch
Passive immunotherapies against HIV-1 will most likely require broadly neutralizing antibodies (bnAb) with maximum breadth and potency to assure therapeutic efficacy. Recently, the novel CD4 binding site antibody N6 demonstrated extraordinary neutralization breadth and potency against large panels of cross clade pseudoviruses. We evaluated the in-vivo antiviral activity of N6-LS, alone or in combination with the established V3-glycan antibody PGT121, in chronically SHIV-SF162P3 infected macaques. A single dose of N6-LS suppressed plasma viral loads in 4 out of 5 animals at day 7 (mean 1...
May 24, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28539447/a-map-of-the-arenavirus-nucleoprotein-host-protein-interactome-reveals-that-jun%C3%A3-n-virus-selectively-impairs-the-antiviral-activity-of-pkr
#9
Benjamin R King, Dylan Hershkowitz, Philip L Eisenhauer, Marion E Weir, Christopher M Ziegler, Joanne Russo, Emily A Bruce, Bryan A Ballif, Jason Botten
Arenaviruses are enveloped negative-strand RNA viruses that cause significant human disease. Encoding only four proteins to accomplish the viral life cycle, each arenavirus protein likely plays unappreciated accessory roles during infection. Here, we used immunoprecipitation and mass spectrometry to identify human proteins that interact with the nucleoprotein (NP) of the Old World arenavirus lymphocytic choriomeningitis (LCMV) and the New World arenavirus Junín Candid #1 (JUNV). Bioinformatic analysis of the identified protein partners of NP revealed that host translation appears to be a key biological process engaged during infection...
May 24, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28539446/infectious-prions-in-the-pregnancy-microenvironment-of-cwd-infected-reeves-muntjac-deer
#10
Amy V Nalls, Erin McNulty, Clare E Hoover, Laura A Pulscher, Edward A Hoover, Candace K Mathiason
Ample evidence exists for the presence of infectious agents at the maternal-fetal interface, often with grave outcomes to the developing fetus (i.e. zika virus, brucella, cytomegalovirus, toxoplasma). While less studied, pregnancy-related transmissible spongiform encephalopathies (TSEs) have been implicated in several species, including humans. Our previous work has shown that prions can be transferred from mother-to-offspring resulting in the development of clinical TSE disease in offspring born to CWD-infected muntjac dams (64)...
May 24, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28539445/structure-of-simian-immunodeficiency-virus-envelope-spikes-bound-with-cd4-and-monoclonal-antibody-36d5
#11
Guiqing Hu, Jun Liu, Kenneth H Roux, Kenneth A Taylor
The HIV-1/SIV envelope spike (Env) mediates the viral entry into host cells. The V3 loop of the gp120 component of the Env trimer contributes to the co-receptor binding site and is a target for neutralizing antibodies. We have used cryoelectron tomography to visualize the binding of CD4 and the V3 loop monoclonal antibody 36D5 to gp120 of the SIV Env. Our results show that 36D5 binds gp120 at the base of the V3 loop and suggest the antibody exerts its neutralization effect by blocking the co-receptor binding site...
May 24, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28539444/improved-prefusion-stability-optimized-codon-usage-and-augmented-virion-packaging-enhance-the-immunogenicity-of-respiratory-syncytial-virus-rsv-fusion-protein-in-a-vectored-vaccine-candidate
#12
Bo Liang, Joan O Ngwuta, Sonja Surman, Barbora Kabatova, Xiang Liu, Matthias Lingemann, Xueqiao Liu, Lijuan Yang, Richard Herbert, Joanna Swerczek, Man Chen, Syed M Moin, Azad Kumar, Jason S McLellan, Peter D Kwong, Barney S Graham, Peter L Collins, Shirin Munir
Respiratory syncytial virus (RSV) is the most important viral agent of severe pediatric respiratory tract disease worldwide, but lacks a licensed vaccine or suitable antiviral drug. A live-attenuated chimeric bovine/human parainfluenza virus type-3 (rB/HPIV3) was developed previously as a vector expressing RSV fusion (F) protein to confer bivalent protection against RSV and HPIV3. In a previous clinical trial in virus-naïve children, rB/HPIV3 was well-tolerated but the immunogenicity of wildtype RSV F was unsatisfactory...
May 24, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28539443/heparan-sulfate-proteoglycan-is-an-important-attachment-factor-for-cell-entry-of-akabane-and-schmallenberg-viruses
#13
Shin Murakami, Akiko Takenaka-Uema, Tomoya Kobayashi, Kentaro Kato, Masayuki Shimojima, Massimo Palmarini, Taisuke Horimoto
Akabane (AKAV) and Schmallenberg (SBV) viruses are Orthobunyavirus transmitted by arthropod vectors with a broad cellular tropism in vitro as well as in vivo Both AKAV and SBV cause arthrogryposis-hydranencephaly syndrome in ruminants. The main cellular receptor and attachment factor for entry of these orthobunyaviruses are unknown. Here, we found that AKAV and SBV infections were inhibited by the addition of heparin or enzymatic removal of cell surface heparan sulfates. To confirm this finding, we prepared heparan sulfate proteoglycan (HSPG)-knockout (KO) cells by using a CRISPR/Cas9 system and measured the binding quantities of these viruses to cell surfaces...
May 24, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28539442/extracellular-interactions-between-hepatitis-c-virus-and-secreted-apolipoprotein-e
#14
Zhihua Li, Yadong Li, Yanwei Bi, Hui Zhang, Yufeng Yao, Qihan Li, Wei Cun, Shaozhong Dong
Interactions between hepatitis C virus (HCV) and lipoproteins in humans play an important role in the efficient establishment of chronic infection. Apolipoprotein E (ApoE) on the HCV envelope mediates virus attachment to host cells as well as immune evasion. This interaction is thought to occur in hepatocytes, as ApoE plays dual functions in HCV assembly and maturation as well as cell attachment. In the present study, we found that secreted ApoE (sApoE) can also bind to viral particles via its C-terminal domain after HCV is released from the cell...
May 24, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28539441/chikungunya-virus-overcomes-polyamine-depletion-by-mutation-of-nsp1-and-the-opal-stop-codon-to-confer-enhanced-replication-and-fitness
#15
Bryan C Mounce, Teresa Cesaro, Lea Vlajnić, Anna Vidiņa, Thomas Vallet, James Weger-Lucarelli, Gabriella Pasoni, Kenneth A Stapleford, Jean-Pierre Levraud, Marco Vignuzzi
Polyamines, small positively-charge molecules present in all cells, play important roles in the replication of DNA and RNA viruses. Chikungunya virus (CHIKV) relies on polyamines for translation of the viral genome upon viral entry, and pharmacological depletion of polyamines limits viral replication. However, the potential development of antiviral resistance necessitates a better understanding of how polyamines function and can be targeted via compounds that alter polyamine levels. We have isolated CHIKV that is resistant to polyamine depletion that contains two mutations in the non-structural protein 1 (nsP1) coding region in combination with mutation to the opal stop codon preceding nsP4...
May 24, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28539440/uncovering-the-repertoire-of-endogenous-flaviviral-elements-in-aedes-mosquito-genomes
#16
Yasutsugu Suzuki, Lionel Frangeul, Laura B Dickson, Hervé Blanc, Yann Verdier, Joelle Vinh, Louis Lambrechts, Maria-Carla Saleh
Endogenous viral elements derived from non-retroviral RNA viruses were described in various animal genomes. Whether they have a biological function such as host immune protection against related viruses is a field of intense study. Here, we investigated the repertoire of endogenous flaviviral elements (EFVEs) in Aedes mosquitoes, the vectors of arboviruses such as dengue and chikungunya viruses. Previous studies identified three EFVEs from Ae. albopictus and one from Ae. aegypti cell lines. However, in-depth characterization of EFVEs in wild-type mosquito populations and individuals in vivo has not been performed...
May 24, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28539439/contribution-of-human-lung-parenchyma-and-leukocyte-influx-to-oxidative-stress-and-immune-mediated-pathology-following-nipah-infection
#17
Olivier Escaffre, Tais B Saito, Terry L Juelich, Tetsuro Ikegami, Jennifer K Smith, David D Perez, Colm Atkins, Corri B Levine, Matthew B Huante, Rebecca J Nusbaum, Janice J Endsley, Alexander N Freiberg, Barry Rockx
Nipah virus (NiV) is a zoonotic emerging paramyxovirus that can cause a fatal respiratory illness or encephalitis in humans. Despite many efforts, the molecular mechanisms of NiV-induced acute lung injury (ALI) remain unclear. We previously showed that NiV replicates to high titers in human lung grafts in NOD scid gamma mice, resulting in a robust inflammatory response. Interestingly, these mice can undergo human immune system reconstitution by the Bone marrow, Liver, and Thymus (BLT) reconstitution method, in addition to lung tissue engraftment, giving altogether a realistic model to study human respiratory viral infections...
May 24, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28539438/discovery-of-a-prefusion-rsv-f-specific-monoclonal-antibody-that-provides-greater-in-vivo-protection-than-the-murine-precursor-of-palivizumab
#18
Min Zhao, Zi-Zheng Zheng, Man Chen, Kayvon Modjarrad, Wei Zhang, Lu-Ting Zhan, Jian-Li Cao, Yong-Peng Sun, Jason S McLellan, Barney S Graham, Ning-Shao Xia
Palivizumab, a humanized murine monoclonal antibody that recognizes antigenic site II on both the prefusion (pre-F) and postfusion (post-F) conformations of the RSV F glycoprotein, is the only prophylactic agent approved for RSV. However, its relatively low neutralizing potency and high cost has limited its use to a restricted population of infants at high risk of severe disease. Previously, we isolated a high potency neutralizing antibody, 5C4, that specifically recognizes antigenic site Ø at the apex of the pre-F trimer...
May 24, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28539437/spontaneous-mutation-at-amino-acid-544-of-the-ebola-glycoprotein-potentiates-virus-entry-and-selection-in-tissue-culture
#19
John B Ruedas, Jason Ladner, Chelsea R Ettinger, Suryaram Gummuluru, Gustavo Palacios, John H Connor
Ebolaviruses have a surface glycoprotein (GP1,2) required for virus attachment and entry into cells. Mutations affecting GP1,2 functions can alter virus growth properties. We generated a recombinant vesicular stomatitis virus encoding Ebola Virus Makona variant GP1,2 (rVSV-MAK-GP) and observed emergence of a T544I mutation in the Makona GP1,2 gene during tissue culture passage in certain cell lines. The T544I mutation emerged within two passages when VSV-MAK-GP was grown on Vero E6, Vero, and BS-C-1 cells but not when it was passaged on Huh7 and HepG2 cells...
May 24, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28515305/cell-cycle-dependent-expression-of-aav2-rep-in-hsv-1-co-infections-gives-rise-to-a-mosaic-of-cells-replicating-either-aav2-or-hsv-1
#20
Francesca D Franzoso, Michael Seyffert, Rebecca Vogel, Artur Yakimovich, Bruna de Andrade Pereira, Anita F Meier, Sereina O Sutter, Kurt Tobler, Bernd Vogt, Urs F Greber, Hildegard Büning, Mathias Ackermann, Cornel Fraefel
Adeno-associated virus 2 (AAV2) depends for productive replication on the simultaneous presence of a helper virus such as herpes simplex virus type 1 (HSV-1). At the same time, AAV2 efficiently blocks the replication of HSV-1, which would eventually limit its own replication by diminishing the helper virus reservoir. This discrepancy begs the question how AAV2 and HSV-1 can co-exist in a cell population. Here we show that in co-infected cultures, AAV2 DNA replication takes place almost exclusively in S/G2 cells, while HSV-1 DNA replication is restricted to G1...
May 17, 2017: Journal of Virology
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