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Journal of Virology

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https://www.readbyqxmd.com/read/29321334/mechanism-of-hiv-1-resistance-to-an-electronically-constrained-%C3%AE-helical-peptide-membrane-fusion-inhibitor
#1
Xiyuan Wu, Zixuan Liu, Xiaohui Ding, Danwei Yu, Huamian Wei, Bo Qin, Yuanmei Zhu, Huihui Chong, Sheng Cui, Yuxian He
SC29EK is an electronically constrained α-helical peptide HIV-1 fusion inhibitor highly effective against both wild-type and enfuvirtide (T20)-resistant viruses. In this study, we focused on investigating the mechanism of HIV-1 resistance to SC29EK by two approaches. First, SC29EK-escaping HIV-1 variants were selected and characterized. Three mutant viruses, which possessed two (E43K/E49A) or three (Q39R/N43K/N126K, N43K/E49A/N126K) amino acid substitutions in the N- and C-terminal repeat regions of gp41 were identified as conferring high resistance to SC29EK and cross-resistance to the first-generation (T20, C34) and newly-designed (sifuvirtide, MT-SC29EK, 2P23) fusion inhibitors...
January 10, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29321333/microrna-130a-regulates-both-hcv-and-hbv-replication-through-a-central-metabolic-pathway
#2
Xiaoqiong Duan, Shilin Li, Jacinta A Holmes, Zeng Tu, Yujia Li, Dachuan Cai, Xiao Liu, Wenting Li, Chunhui Yang, Baihai Jiao, Esperance A Schaefer, Dahlene N Fusco, Shadi Salloum, Limin Chen, Wenyu Lin, Raymond T Chung
BACKGROUND: HCV infection has been shown to regulate miR-130a in patient biopsies and in cultured cells. We sought to identify miR-130a target genes and to explore the mechanisms by which miR-130a regulates HCV and HBV replication.METHODS: We used bioinformatics software including miRanda, TargetScan, PITA and RNAhybrid to predict potential miR-130a target genes. miR-130a and its target genes were overexpressed, or knocked down by siRNA or by CRISPR/Cas9 gRNA, respectively. Selected gene mRNAs and their proteins, together with HCV replication in OR6 cells, JFH1 HCV-infected Huh7...
January 10, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29321332/erk-is-a-critical-regulator-of-jc-polyomavirus-infection
#3
Jeanne K DuShane, Michael P Wilczek, Colleen L Mayberry, Melissa S Maginnis
The human JC polyomavirus (JCPyV) infects the majority of the population worldwide and presents as an asymptomatic, persistent infection in the kidney. In individuals who are immunocompromised, JCPyV can become reactivated and cause a lytic infection in the central nervous system resulting in the fatal, demyelinating disease progressive multifocal leukoencephalopathy (PML). Infection is initiated by interactions between the capsid protein viral protein 1 (VP1) and the α2,6-linked sialic acid on LSTc, while JCPyV internalization is facilitated by 5-hydroxytryptamine 2 receptors (5-HT2Rs)...
January 10, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29321331/germline-igm-is-sufficient-but-not-required-for-antibody-mediated-alphavirus-clearance-from-the-central-nervous-system
#4
Voraphoj Nilaratanakul, Jie Chen, Oanh Tran, Victoria K Baxter, Elizabeth M Troisi, Jane X Yeh, Diane E Griffin
Sindbis virus (SINV) infection of neurons in the brain and spinal cord in mice provides a model system for investigating recovery from encephalomyelitis and antibody-mediated clearance of virus from the central nervous system (CNS). To determine the roles of IgM and IgG in recovery, we compared the responses of immunoglobulin-deficient activation-induced adenosine deaminase (AID)-/-, secretory IgM (sIgM)-/- and AID-/- sIgM-/- double knock out (DKO) mice with wild-type (WT) C57BL/6 mice for disease, clearance of infectious virus and viral RNA from brain and spinal cord, antibody responses and B cell infiltration into the CNS...
January 10, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29321330/glycosyl-phosphatidylinositol-anchored-anti-hiv-env-single-chain-variable-fragments-interfere-with-hiv-1-env-processing-and-viral-infectivity
#5
Anisha Misra, Emile Gleeson, Weiming Wang, Chaobaihui Ye, Paul Zhou, Jason T Kimata
In previous studies, we demonstrated that single-chain variable fragments (scFv) from anti-HIV Env monoclonal antibodies act as entry inhibitors when tethered to the surface of target cells by a glycosyl-phosphitidylinositol (GPI) anchor. Interestingly, even if a virus escapes inhibition at entry, its replication is ultimately controlled. We hypothesized that in addition to functioning as entry inhibitors, anti-HIV GPI-scFvs may also interact with Env in an infected cell, thereby interfering with infectivity of newly produced virions...
January 10, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29321329/a-cyclin-binding-motif-in-human-samhd1-is-required-for-its-hiv-1-restriction-dntpase-activity-tetramer-formation-and-efficient-phosphorylation
#6
Corine St Gelais, Sun Hee Kim, Victoria V Maksimova, Olga Buzovetsky, Kirsten Knecht, Caitlin Shepard, Baek Kim, Yong Xiong, Li Wu
Sterile alpha motif and HD domain-containing protein 1 (SAMHD1) regulates intracellular deoxynucleoside triphosphate (dNTP) levels and functions as a retroviral restriction factor through its dNTP triphosphohydrolase (dNTPase) activity. Human SAMHD1 interacts with cell cycle regulatory proteins cyclin A2, cyclin-dependent kinase 1 (CDK1), and CDK2. This interaction mediates phosphorylation of SAMHD1 at threonine 592 (T592), which negatively regulates HIV-1 restriction. We previously reported that the interaction is mediated, at least in part, through a cyclin-binding motif (RXL, aa...
January 10, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29321328/activities-of-thrombin-and-factor-xa-are-essential-for-replication-of-hepatitis-e-virus-and-are-possibly-implicated-in-the-orf1-polyprotein-processing
#7
Gayatri D Kanade, Kunal D Pingale, Yogesh A Karpe
Hepatitis E virus (HEV) is a clinically important positive-sense RNA virus. The ORF1 of HEV encodes a non-structural polyprotein of 1693 amino acids. It is not clear whether the ORF1 polyprotein is processed into distinct enzymatic domains. Many researchers have attempted to understand the mechanisms of pORF1 processing. However, these studies gave varied results and could never convincingly establish the mechanism of pORF1 processing. In this study, we demonstrated the possible role of thrombin and factor Xa in pORF1 processing...
January 10, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29321327/human-papillomavirus-16-infection-induces-vap-dependent-endosomal-tubulation
#8
Abida Siddiqa, Paola Massimi, David Pim, Justyna Broniarczyk, Lawrence Banks
Human Papillomavirus (HPV) infection involves complex interactions with the endocytic transport machinery, which ultimately facilitates the entry of the incoming viral genomes into the trans-Golgi network and their subsequent nuclear entry during mitosis. The endosomal pathway is a highly dynamic intracellular transport system, which consists of vesicular compartments and tubular extensions, although it is currently unclear whether incoming viruses specifically alter the endocytic machinery. In this study, using MICAL-L1 as a marker for tubulating endosomes, we show that incoming HPV-16 virions induce a profound alteration in global levels of endocytic tubulation...
January 10, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29321326/the-amino-terminus-of-hsv-1-glycoprotein-k-gk-is-required-for-gb-binding-to-akt-release-of-intracellular-calcium-and-fusion-of-the-viral-envelope-with-plasma-membranes
#9
Farhana Musarrat, Nithya Jambunathan, Paul J F Rider, V N Chouljenko, K G Kousoulas
Previously, we have shown that the amino terminus of glycoprotein K (gK) binds to the amino terminus of gB and that deletion of the amino terminal 38 amino acids of gK prevents virus infection of mouse trigeminal ganglia after ocular infection and virus entry into neuronal axons. Recently, it has been shown that gB binds to Akt during virus entry and induces Akt phosphorylation and intracellular calcium release. Proximity ligation and two-way immunoprecipitation assays using monoclonal antibodies against gB and Akt-1 (phospho S473) confirmed that HSV-1(McKrae) gB interacted with Akt-1 (phospo S473) during virus entry into human neuroblastoma (SK-N-SH) cells and induced release of intracellular calcium...
January 10, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29321325/the-identification-and-characterization-of-sindbis-virus-rna-host-protein-interactions
#10
Autumn T LaPointe, Natasha N Gebhart, Megan E Meller, Richard W Hardy, Kevin J Sokoloski
Arthropod-borne viruses, such as the members of genus Alphavirus, are a significant concern to global public health. As obligate intracellular pathogens, RNA viruses must interact with the host cell machinery to establish, and complete, their viral lifecycles. Despite considerable efforts to define the host/pathogen interactions essential for alphaviral replication, an unbiased and inclusive assessment of alphaviral RNA:protein interactions has not been undertaken. Moreover, the biological and molecular importance of these interactions, in the full context of their molecular function as RNA-binding proteins, has not been fully realized...
January 10, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29321324/influenza-c-and-d-viruses-package-eight-organized-ribonucleoprotein-complexes
#11
Sumiho Nakatsu, Shin Murakami, Keiko Shindo, Taisuke Horimoto, Hiroshi Sagara, Takeshi Noda, Yoshihiro Kawaoka
Influenza A and B viruses have eight-segmented, single-stranded, negative-sense RNA genomes, whereas influenza C and D viruses have seven-segmented genomes. Each genomic RNA segment exists in the form of a ribonucleoprotein complex (RNP) in association with nucleoproteins and an RNA-dependent RNA polymerase in virions. Influenza D virus was recently isolated from swine and cattle, but its morphology is not fully studied. Here, we examined the morphological characteristics of D/bovine/Yamagata/10710/2016 (D/Yamagata) and C/Ann Arbor/50 (C/AA), focusing on RNPs packaged within the virions...
January 10, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29321323/hiv-1-vif-s-capacity-to-manipulate-the-cell-cycle-is-species-specific
#12
Edward L Evans, Jordan T Becker, Stephanie L Fricke, Kishan Patel, Nathan M Sherer
Cells derived from mice and other rodents exhibit profound blocks to HIV-1 virion production reflecting species-specific incompatibilities between viral Tat and Rev proteins and essential host factors Cyclin T1 (CCNT1) and Exportin-1 (XPO1, also known as CRM1), respectively. To determine if mouse cell blocks other than CCNT1 and XPO1 affect HIV's post-integration stages, we studied HIV-1NL4-3 gene expression in mouse NIH 3T3 cells modified to constitutively express HIV-1 compatible versions of CCNT1 and XPO1 (3T3...
January 10, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29321322/dengue-virus-selectively-annexes-endoplasmic-reticulum-associated-translation-machinery-as-a-strategy-for-co-opting-host-cell-protein-synthesis
#13
David W Reid, Rafael K Campos, Jessica R Child, Tianli Zheng, Kitti Wing Ki Chan, Shelton S Bradrick, Subhash G Vasudevan, Mariano A Garcia-Blanco, Christopher V Nicchitta
A primary question in Dengue virus (DENV) biology is the molecular strategy for recruitment of host cell protein synthesis machinery. Here we combined cell fractionation, ribosome profiling, and RNA-seq to investigate the subcellular organization of viral genome translation and replication as well as host cell translation and its response to DENV infection. We report that throughout the viral life cycle, DENV (+) and (-) strand RNAs were highly partitioned to the endoplasmic reticulum (ER), identifying the ER as the primary site of DENV translation...
January 10, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29321321/functional-analysis-of-the-dengue-virus-genome-using-an-insertional-mutagenesis-screen
#14
Jeffrey W Perry, Yanhua Chen, Elizabeth Speliotes, Andrew W Tai
In the last few decades, dengue virus, an arbovirus, has spread to over 120 countries. Although a vaccine has been approved in some countries, limitations on its effectiveness, and a lack of effective antiviral treatments reinforce the need for additional research. The functions of several viral nonstructural proteins are essentially unknown. To better understand the functions of these proteins and thus dengue virus pathogenesis, we embarked on a genome wide transposon mutagenesis screen with Next Generation Sequencing to determine sites in the viral genome that tolerate 15 nucleotide insertions...
January 10, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29321320/hiv-1-specific-iga-monoclonal-antibodies-from-an-hiv-1-vaccinee-mediate-galcer-blocking-and-phagocytosis
#15
Saintedym Wills, Kwan-Ki Hwang, Pinghuang Liu, S Moses Dennison, Matthew Zirui Tay, Xiaoying Shen, Justin Pollara, Judith T Lucas, Robert Parks, Supachai Rerks-Ngarm, Punnee Pitisuttithum, Sorachai Nitayapan, Jaranit Kaewkungwal, Rasmi Thomas, Jerome H Kim, Nelson L Michael, Merlin L Robb, Mike McRaven, David C Montefiori, Thomas J Hope, Hua-Xin Liao, M Anthony Moody, Guido Ferrari, Barton F Haynes, S Munir Alam, Mattia Bonsignori, Georgia D Tomaras
Vaccine-elicited humoral immune responses comprise an array of antibody forms and specificities with only a fraction contributing to protective host immunity. Elucidation of antibody effector functions responsible for protective immunity against HIV-1 acquisition is a major goal for the HIV-1 vaccine field. Immunoglobulin A (IgA) is an important part of the host defense against pathogens; however, little is known about the role of vaccine-elicited IgA and their capacity to mediate antiviral functions. To identify the antiviral functions of HIV-1-specific IgA elicited by vaccination, we cloned HIV-1 envelope specific IgA monoclonal antibodies by memory B cell cultures from peripheral blood mononuclear cells from an RV144 vaccinee and produced two IgA clonal cell lines (HG129 and HG130) producing native, non-recombinant IgA monoclonal antibodies (mAbs)...
January 10, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29321319/non-structural-protein-%C3%AF-1s-is-required-for-optimal-reovirus-protein-expression
#16
Matthew B Phillips, Johnasha D Stuart, Emily J Simon, Karl W Boehme
Reovirus non-structural protein σ1s is required for the establishment of viremia and hematogenous viral dissemination. However, the function of the σ1s protein during the reovirus replication cycle is not known. In this study, we found that σ1s was required for efficient reovirus replication in SV40-immortalized endothelial cells (SVECs), mouse embryonic fibroblasts, human umbilical vein endothelial cells (HUVECs), and T84 human colonic epithelial cells. In each of these cell lines, wild type reovirus produced substantially higher viral titers than a σ1s-deficient mutant...
January 10, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29321318/viperin-restricts-zika-virus-and-tick-borne-encephalitis-virus-replication-by-targeting-ns3-for-proteasomal-degradation
#17
Christakis Panayiotou, Richard Lindqvist, Chaitanya Kurhade, Kirstin Vonderstein, Jenny Pasto, Karin Edlund, Arunkumar S Upadhyay, Anna K Överby
Flaviviruses are arthropod-borne viruses that constitute a major global health problem, with millions of human infections annually. Their pathogenesis ranges from mild illness to severe manifestations such as hemorrhagic fever and fatal encephalitis. Type I interferons (IFNs) are induced in response to viral infection, and stimulate the expression of interferon-stimulated genes (ISGs), including that encoding viperin (virus-inhibitory protein, endoplasmic reticulum-associated, IFN-inducible), which shows antiviral activity against a broad spectrum of viruses including several flaviviruses...
January 10, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29321317/the-wnt-signaling-pathway-is-differentially-expressed-during-the-bovine-herpesvirus-1-latency-reactivation-cycle-evidence-that-two-protein-kinases-associated-with-neuronal-survival-akt3-and-bone-morphogenetic-protein-receptor-2-are-expressed-at-higher-levels
#18
Aspen Workman, Liqian Zhu, Brittney N Keel, Timothy P L Smith, Clinton Jones
Sensory neurons in trigeminal ganglia (TG) of calves latently infected with bovine herpesvirus 1 (BoHV-1) abundantly express latency-related (LR) gene products, including a protein (ORF2) and two micro-RNAs. Recent studies in mouse neuroblastoma cells (Neuro-2A) demonstrated ORF2 interacts with β-catenin and a β-catenin coactivator, high mobility group AT-hook 1 protein (HMGA1), which correlates with increased β-catenin dependent transcription and cell survival. β-catenin and HMGA1 are readily detected in a subset of latently infected TG neurons, but not TG neurons from uninfected calves or reactivation from latency...
January 10, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29321316/two-residues-in-nsp9-contribute-to-the-enhanced-replication-and-pathogenicity-of-highly-pathogenic-porcine-reproductive-and-respiratory-syndrome-virus
#19
Kuan Zhao, Jia-Cong Gao, Jun-Yao Xiong, Jin-Chao Guo, Yong-Bo Yang, Cheng-Gang Jiang, Yan-Dong Tang, Zhi-Jun Tian, Xue-Hui Cai, Guang-Zhi Tong, Tong-Qing An
Highly pathogenic porcine reproductive and respiratory syndrome virus (HP-PRRSV) possesses greater replicative capacity and pathogenicity than classical PRRSV. However, the factors that lead to enhanced replication and pathogenicity remain unclear. In our study, an alignment of all available full-length sequences of North-American type PRRSVs (n = 204) revealed two consistent amino acid mutations that differed between HP-PRRSV and classical PRRSV and were located at positions 519 and 544 in non-structural protein 9...
January 10, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29321315/paramyxovirus-v-proteins-interact-with-the-rig-i-trim25-regulatory-complex-and-inhibit-rig-i-signaling
#20
Maria T Sanchez-Aparicio, Leighland J Feinman, Adolfo García-Sastre, Megan L Shaw
Paramyxovirus V proteins are known antagonists of the RIG-I-like receptor (RLR)-mediated interferon induction pathway, interacting with and inhibiting the RLR MDA5. We report interactions between the Nipah virus V protein and both the RIG-I regulatory protein, TRIM25, and RIG-I. We also observed interactions between these host proteins and the V proteins of measles virus, Sendai virus and parainfluenza virus. These interactions are mediated by the conserved C-terminal domain of the V protein, which binds to the tandem CARDs of RIG-I (the region of TRIM25-ubiquitination) and to the SPRY domain of TRIM25, which mediates TRIM25 interaction with the RIG-I CARDs...
January 10, 2018: Journal of Virology
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