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Jennifer C Chmura, Kevin Herold, Ayana Ruffin, Trudymae Atuobi, Yetunde Fabiyi, Ashley E Mitchell, Young Bong Choi, Elana S Ehrlich
Expression of Kaposi's sarcoma herpesvirus vFLIP, a potent activator of NFkB signaling, promotes latency. Inhibition of NFkB signaling promotes lytic reactivation. We previously reported that lytic inducer, RTA, inhibits vFLIP induced NFkB signaling by inducing the degradation of vFLIP via the proteasome. Here we report that the cellular ubiquitin ligase, Itch, is required for RTA induced degradation of vFLIP. Expression of either Itch targeting shRNA or a dominant negative mutant of the ubiquitin ligase both increased the stability of vFLIP in the presence of RTA...
November 29, 2016: Virology
Shuang Hu, Charles Preston Neff, Dipu Mohan Kumar, Yuichiro Habu, Sarah R Akkina, Takahiro Seki, Ramesh Akkina
While HIV-2 is a causative agent for AIDS in addition to the better studied HIV-1, there is currently no suitable animal model for experimental studies for HIV-2 infection and evaluating promising drugs in vivo. Here we evaluated humanized mice for their susceptibility to HIV-2 infection and tested a single-pill three drug formulation of anti-retrovirals (NRTIs abacavir and lamivudine, integrase inhibitor dolutegravir) (trade name, Triumeq(R)). Our results showed that hu-mice are susceptible to HIV-2 infection showing persistent viremia and CD4 T cell loss, key hallmarks of AIDS pathogenesis...
November 29, 2016: Virology
Sara E Reynolds, Patricia L Earl, Mahnaz Minai, Ian Moore, Bernard Moss
Most poxviruses encode a homolog of a ~200,000-kDa membrane protein originally identified in variola virus. We investigated the importance of the ectromelia virus (ECTV) homolog C15 in a natural infection model. In cultured mouse cells, the replication of a mutant virus with stop codons near the N-terminus (ECTV-C15Stop) was indistinguishable from a control virus (ECTV-C15Rev). However, for a range of doses injected into the footpads of BALB/c mice there was less mortality with the mutant. Similar virus loads were present at the site of infection with mutant or control virus whereas there was less ECTV-C15Stop in popliteal and inguinal lymph nodes, spleen and liver indicating decreased virus spread and replication...
November 26, 2016: Virology
Luca Popescu, Natasha N Gaudreault, Kristen M Whitworth, Maria V Murgia, Jerome C Nietfeld, Alan Mileham, Melissa Samuel, Kevin D Wells, Randall S Prather, Raymond R R Rowland
African swine fever is a highly contagious, often fatal disease of swine for which there is no vaccine or other curative treatment. The macrophage marker, CD163, is a putative receptor for African swine fever virus (ASFV). Pigs possessing a complete knockout of CD163 on macrophages were inoculated with Georgia 2007/1, a genotype 2 isolate. Knockout and wild type pen mates became infected and showed no differences in clinical signs, mortality, pathology or viremia. There was also no difference following in vitro infection of macrophages...
November 26, 2016: Virology
Meng Hu, Shuofeng Yuan, Ke Zhang, Kailash Singh, Qiang Ma, Jie Zhou, Hin Chu, Bo-Jian Zheng
PB2 is one of the subunits of the influenza A virus (IAV) polymerase complex. By bioinformatics analysis we identified PB2 substitutions at positions 389 and 598 among IAV isolates from humans, which might associate with viral pathogenicity. To evaluate the biological significance of these substitutions, PB2-K389R and -V598T/I mutant viruses of avian H7N9 IAVs were generated by reverse genetics. Compared to the wild type, the mutant viruses displayed an enhanced growth capacity in human and mammalian cells...
November 24, 2016: Virology
Junrong Luo, Lucas Ferguson, David R Smith, Amelia R Woolums, William B Epperson, Xiu-Feng Wan
Influenza D virus (IDV), a new member of the influenza virus family, was first reported in 2011 in swine in Oklahoma, USA, and then soon found in cattle across North America and Eurasia. Earlier studies suggested cattle serve as natural reservoir for IDV. The goal of this study is to perform a retrospective study looking at sera collected from Nebraska beef herds in 2003-2004 and 2014 for evidence of IDV antibodies. Results showed that all 40 randomly selected farms (2003-2004) we tested contained IDV seropositive adult animals and that approximately 98% of newborn calves (2014) had high levels of maternal antibodies against IDV...
November 23, 2016: Virology
Chee Wah Tan, I-Ching Sam, Vannajan Sanghiran Lee, Hui Vern Wong, Yoke Fun Chan
Enterovirus A71 (EV-A71) is a neurotropic enterovirus that uses heparan sulfate as an attachment receptor. The molecular determinants of EV-A71-heparan sulfate interaction are unknown. With In silico heparin docking and mutagenesis of all possible lysine residues in VP1, we identified that K162, K242 and K244 are responsible for heparin interaction and inhibition. EV-A71 mutants with K242A and K244A rapidly acquired compensatory mutations, T100K or E98A, and Q145R-T237N respectively, which restored the heparin-binding phenotype...
November 19, 2016: Virology
Danielle Colledge, Sally Soppe, Lilly Yuen, Lucy Selleck, Renae Walsh, Stephen Locarnini, Nadia Warner
Premature stop codons in the hepatitis B virus (HBV) surface protein can be associated with nucleos(t)ide analogue resistance due to overlap of the HBV surface and polymerase genes. The aim of this study was to determine the effect of the replication of three common surface stop codon variants on the hepatocyte. Cell lines were transfected with infectious HBV clones encoding surface stop codons rtM204I/sW196*, rtA181T/sW172*, rtV191I/sW182*, and a panel of substitutions in the surface proteins. HBsAg was measured by Western blotting...
November 18, 2016: Virology
Angel E Absalón, Andrés Morales-Garzón, Pedro F Vera-Hernández, Diana V Cortés-Espinosa, Sara M Uribe-Ochoa, Laura J García, Eduardo Lucio-Decanini
In this study, we conducted the clinicopathological characterization of a non-pathogenic FAdV-D serotype 11 strain MX95, isolated from healthy chickens, and its entire genome was sequenced. Experiments in SPF chickens revealed that the strain is a non-pathogenic virus that did not cause death at challenge doses of 1×10(6) TCID50. Additionally, the infection in SPF chickens caused no apparent damage in most of the organs analyzed by necropsy and histopathology, but it did cause inclusion body hepatitis; nevertheless it did not generate severe infectious clinical symptoms...
November 17, 2016: Virology
Danielle K Offerdahl, David W Dorward, Bryan T Hansen, Marshall E Bloom
The Zika virus (ZIKV) pandemic is a global concern due to its role in the development of congenital anomalies of the central nervous system. This mosquito-borne flavivirus alternates between mammalian and mosquito hosts, but information about the biogenesis of ZIKV is limited. Using a human neuroblastoma cell line (SK-N-SH) and an Aedes albopictus mosquito cell line (C6/36), we characterized ZIKV infection by immunofluorescence, transmission electron microscopy (TEM), and electron tomography (ET) to better understand infection in these disparate host cells...
November 15, 2016: Virology
Tsai-Ling Ho, Hsiang-Chi Lee, Yuan-Lin Chou, Yang-Hao Tseng, Wei-Cheng Huang, Chiung-Hua Wung, Na-Sheng Lin, Yau-Heiu Hsu, Ban-Yang Chang
The movement of some plant viruses are accomplished by three proteins encoded by a triple gene block (TGB). The second protein (TGBp2) in the block is a transmembrane protein. This study was aimed to unravel the mechanism underlying the relatively inefficient cell-to-cell movement of Bamboo mosaic virus (BaMV) caused by amino acid substitutions for the three Cys residues, Cys-109, Cys-112 and Cys-119, at the C-terminal tail of TGBp2. Results from confocal microscopy revealed that substitutions of the three Cys residues of TGBp2, especially Cys-109 and Cys-112, would reduce the efficiency of TGBp2- and TGBp3-dependent PD localization of TGBp1...
November 15, 2016: Virology
Bénédicte Vanwalscappel, Sylvie Rato, Mayte Perez-Olmeda, Francisco Díez Fuertes, Nicoletta Casartelli, José Alcami, Fabrizio Mammano
Treatment of HIV-infected patients with IFN-α results in significant, but clinically insufficient, reductions of viremia. IFN induces the expression of several antiviral proteins including BST-2, which inhibits HIV by multiple mechanisms. The viral protein Vpu counteracts different effects of BST-2. We thus asked if Vpu proteins from IFN-treated patients displayed improved anti-BST-2 activities as compared to Vpu from baseline. Deep-sequencing analyses revealed that in five of seven patients treated by IFN-α for a concomitant HCV infection in the absence of antiretroviral drugs, the dominant Vpu sequences differed before and during treatment...
November 14, 2016: Virology
Benson Y H Cheng, Aitor Nogales, Juan Carlos de la Torre, Luis Martínez-Sobrido
Several arenaviruses, chiefly Lassa (LASV) in West Africa, cause hemorrhagic fever (HF) disease in humans and pose important public health problems in their endemic regions. To date, there are no FDA-approved arenavirus vaccines and current anti-arenaviral therapy is limited to the use of ribavirin that has very limited efficacy. In this work we document that a recombinant prototypic arenavirus lymphocytic choriomeningitis virus (LCMV) with a codon deoptimized (CD) surface glycoprotein (GP), rLCMV/CD, exhibited wild type (WT)-like growth properties in cultured cells despite barely detectable GP expression levels in rLCMV/CD-infected cells...
November 14, 2016: Virology
Sarah M Doore, Nicholas J Schweers, Bentley A Fane
In an earlier study, protein-based barriers to horizontal gene transfer were investigated by placing the bacteriophage G4 G gene, encoding the major spike protein, into the φX174 genome. The foreign G protein promoted off-pathway assembly reactions, resulting in a lethal phenotype. After three targeted genetic selections, one of two foreign spike proteins was productively integrated into the φX174 system: the complete G4 or a recombinant G4/φX174 protein (94% G4:6% φX174). However, strain fitness was very low...
November 14, 2016: Virology
Thandeka Moyo, Roux-Cil Ferreira, Reyaaz Davids, Zarinah Sonday, Penny L Moore, Simon A Travers, Natasha T Wood, Jeffrey R Dorfman
Glycans on HIV-1 Envelope serve multiple functions including blocking epitopes from antibodies. We show that removal of glycan 301, a major target of anti-V3/glycan antibodies, has substantially different effects in two viruses. While glycan 301 on Du156.12 blocks epitopes commonly recognized by sera from chronically HIV-1-infected individuals, it does not do so on CAP45.G3, suggesting that removing the 301 glycan has a smaller effect on the integrity of the glycan shield in CAP45.G3. Changes in sensitivity to broadly neutralizing monoclonal antibodies suggest that the interaction between glycan 301 and the CD4 binding site differ substantially between these 2 viruses...
November 12, 2016: Virology
Rugang Li, Chellappan Padmanabhan, Kai-Shu Ling
Tomato planta macho viroid (TPMVd), including isolates previously designated as Mexican papita viroid (MPVd), causes serious disease on tomatoes in North America. Two predominant variants, sharing 93.8% sequence identity, incited distinct severe (MPVd-S) or mild (MPVd-M) symptoms on tomato. To identify virulence determinant factor, a series of chimeric infectious clones were generated using synthetic DNA approach to progressively replace each structural domain between the two variants. In bioassays on tomato 'Rutgers', three chimeras containing Terminal Left and Pathogenicity (MPVd-H1), Central (MPVd-H2), or Variable (MPVd-H3) of MPVd-S, incited mild to intermediate symptoms...
November 10, 2016: Virology
María Lago, Isabel Bandín, José G Olveira, Carlos P Dopazo
Reassortment is one of the main mechanisms of evolution in dsRNA viruses with segmented genomes. It contributes to generate genetic diversity and plays an important role in the emergence and spread of new strains with altered virulence. Natural reassorment has been demonstrated among infectious pancreatic necrosis-like viruses (genus Aquabirnavirus, Birnaviridae). In the present study, coinfections between different viral strains, and genome sequencing by the Sanger and Illumina methods were applied to analyze the frequency of reassortment of this virus in vitro, the possible mechanisms involved, and its effect on virulence...
November 10, 2016: Virology
Derek J Schneweis, Anna E Whitfield, Dorith Rotenberg
Tomato spotted wilt virus (TSWV) is transmitted by Frankliniella occidentalis in a circulative-propagative manner. Little is known about thrips vector response to TSWV during the infection process from larval acquisition to adult inoculation of plants. Whole-body transcriptome response to virus infection was determined for first-instar larval, pre-pupal and adult thrips using RNA-Seq. TSWV responsive genes were identified using preliminary sequence of a draft genome of F. occidentalis as a reference and three developmental-stage transcriptomes were assembled...
November 8, 2016: Virology
Amira Zine El Abidine, Vjekoslav Tomaić, Rahima Bel Haj Rhouma, Paola Massimi, Ikram Guizani, Samir Boubaker, Emna Ennaifer, Lawrence Banks
Human Papillomavirus E6 and E7 play critical roles in cancer development, although not all isolates of the viral oncoproteins are identical. A common E7 variant encodes an amino acid change at N29S. We show that this change increases the levels of phosphorylation by CKII by creating an additional phospho-acceptor site at S29. This confers increased phospho-dependent interaction with a number of cellular targets, including TATA Box Binding Protein (TBP) and pRb. A further consequence is an increased ability to target pRb and p130 for degradation...
November 6, 2016: Virology
Jingjing Wang, Ying Zhang, Xiaolong Zhang, Yajie Hu, Chenghong Dong, Longding Liu, Erxia Yang, Yanchun Che, Jing Pu, Xi Wang, Jie Song, Yun Liao, Min Feng, Yan Liang, Ting Zhao, Li Jiang, Zhanlong He, Shuaiyao Lu, Lichun Wang, Yanyan Li, Shengtao Fan, Lei Guo, Qihan Li
Coxsackievirus A16 (CV-A16) causes human hand, foot and mouth disease, but its pathogenesis is unclear. In rhesus macaques, CV-A16 infection causes characteristic vesicles in the oral mucosa and limbs as well as viremia and positive viral loads in the tissues, suggesting that these animals reflect the pathologic process of the infection. An immunologic analysis indicated a defective immune response, which included undetectable neutralizing antibodies and IFN-γ-specific memory T-cells in macaques infected with CV-A16...
November 6, 2016: Virology
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