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June 2018
Human papillomavirus type 16 E5-mediated upregulation of Met in human keratinocytes
Publication date: June 2018
Source:Virology, Volume 519 Author(s): Matthew L. Scott, David T. Coleman, Kinsey C. Kelly, Jennifer L. Carroll, Brittany Woodby, William K. Songock, James A. Cardelli, Jason M. Bodily Human papillomaviruses (HPVs) cause benign lesions that can lead to malignancy. How cellular changes induced by viral oncogenes contribute to the progeny virion production is not always clear. Stromally-derived growth factors and their receptors are critical for development of malignancy, but their impact on the pre-malignant HPV life cycle is unknown. We show that HPV16 increases levels of Met, a growth factor receptor critical for tumor cell invasion, motility, and cancer metastasis. The viral oncogene E5 is primarily responsible for Met upregulation, with E6 playing a minor role. Met induction by E5 requires the epidermal growth factor receptor, which is also increased by E5 at the mRNA level. E5-induced Met contributes motility of HPV-containing cells. Finally, Met signaling is necessary for viral gene expression, particularly in the differentiation-dependent phase of the viral life cycle. These studies show a new role for E5 in epithelial-stromal interactions, with implications for cancer development.
June 2018
Molecular characterization of a novel mycovirus in Alternaria alternata manifesting two-sided effects: Down-regulation of host growth and up-regulation of host plant pathogenicity
Publication date: June 2018
Source:Virology, Volume 519 Author(s): Ryo Okada, Shun Ichinose, Kana Takeshita, Syun-ichi Urayama, Toshiyuki Fukuhara, Ken Komatsu, Tsutomu Arie, Atsushi Ishihara, Mayumi Egusa, Motoichiro Kodama, Hiromitsu Moriyama A double-stranded RNA (dsRNA) mycovirus was detected in a strain of Alternaria alternata showing impaired growth phenotypes. The A. alternata strain is the Japanese pear pathotype, which produces a host-specific AK-toxin. Sequence analysis of the viral genome dsRNAs revealed that this mycovirus consists of five dsRNAs and is evolutionarily related to members of the family Chrysoviridae; the virus was named Alternaria alternata chrysovirus 1 (AaCV1). AaCV1-ORF2 protein accumulated in dsRNA-high-titer sub-isolates with severely impaired phenotypes; heterologous AaCV1-ORF2 overexpression in Saccharomyces cerevisiae caused growth inhibition. In contrast to this yeast growth inhibition phenomenon, the dsRNA-high-titer isolates displayed enhanced pathogenicity against Japanese pear plants, in accordance with a 13-fold increase in AK-toxin level in one such isolate. These findings indicated that AaCV1 is a novel mycovirus that exhibits two contrasting effects, impairing growth of the host fungus while rendering the host hypervirulent to the plant.
June 2018
Novel orthohepeviruses in wild rodents from S
June 2018
The 164
June 2018
Recombinant Flag-tagged E1E2 glycoproteins from three hepatitis C virus genotypes are biologically functional and elicit cross-reactive neutralizing antibodies in mice
Publication date: June 2018
Source:Virology, Volume 519 Author(s): Vasil B. Krapchev, Malgorzata Rych
June 2018
Polymorphisms affecting the gE and gI proteins partly contribute to the virulence of a newly-emergent highly virulent Chinese pseudorabies virus
Publication date: June 2018
Source:Virology, Volume 519 Author(s): Jing Dong, Zhenqing Gu, Ling Jin, Lin Lv, Jichun Wang, Tao Sun, Juan Bai, Haifeng Sun, Xianwei Wang, Ping Jiang An outbreak of a highly virulent pseudorabies virus strain, ZJ01, occurred in PRV-vaccinated pigs in China in 2011. In this study, ZJ01 caused fatal diseases, while the Chinese prototypic PRV strain LA caused mild respiratory disorders. Full-genome sequencing results indicate the two viruses can be classified into two sub-clusters that distinct from traditional European and US strains. To examine the potential role of the gE and gI proteins in ZJ01 virulence, we generated several recombinant viruses. In two chimeric viruses (rZJ01-LA/gEI and rLA-ZJ01/gEI), the gE and gI genes were swapped using corresponding genes from ZJ01 and LA. rZJ01-LA/gEI and the parental virus rZJ01 retained high virulence in piglets, although the survival time for rZJ01-LA/gEI infected piglets was obviously prolonged. In contrast, rLA-ZJ01/gEI exhibited higher virulence than its parental virus rLA. We conclude that changes in gE and gI proteins partly contribute to the enhanced virulence of ZJ01 strain.
June 2018
Jembrana disease virus Vif antagonizes the inhibition of bovine APOBEC3 proteins through ubiquitin-mediate protein degradation
Publication date: June 2018
Source:Virology, Volume 519 Author(s): Xing Su, Hong Wang, Xiaohong Zhou, Zhaolong Li, Baisong Zheng, Wenyan Zhang Viral infectivity factor (Vif) encoded by lentiviruses is essential for viral replication and escaping from antiviral activity of host defensive factors APOBEC3. Jembrana disease virus (JDV) causes an acute disease syndrome with approximately 20% case fatality rate in Bali cattle. However, the interplay mechanism between JDV Vif and Bos taurus APOBEC3 (btA3) is poorly understood. In this study, we determined that JDV Vif recruits ElonginB, ElonginC(ELOB/C), Cul2 and RBX1 but without the need of CBF-
June 2018
Three amino acid substitutions in the NS1 protein change the virus replication of H5N1 influenza virus in human cells
Publication date: June 2018
Source:Virology, Volume 519 Author(s): Jing Li, Kun Zhang, Quanjiao Chen, Xiaoshuang Zhang, Yeping Sun, Yuhai Bi, Shuang Zhang, Jinyan Gu, Jiarong Li, Di Liu, Wenjun Liu, Jiyong Zhou Influenza A viruses have sophisticated strategies to promote their own replication. Here, we found that three H5N1 influenza viruses display different replication patterns in human A549 and macrophage cells. The HN01 virus displayed poor replication compared to HN021 and JS01. In addition, the HN01 virus was unable to counteract the interferon response and block general gene expression. This capability was restored by three amino acid substitutions on the NS1 protein: K55E, K66E, and C133F, resulting in recovered binding to CPSF30 and decreased interferon response activity. Furthermore, a recombinant HN01 virus expressing either NS1-C133F or the triple mutation replicate with higher titers in human A549 cells and macrophages compared to the parent virus. These three amino acid mutations reveal a new pathway to alter H5N1 virus replication.
June 2018
Phosphorodiamidate morpholino targeting the 5
June 2018
Scavenger receptor-mediated Ad5 entry and acLDL accumulation in monocytes/macrophages synergistically trigger innate responses against viral infection
Publication date: June 2018
Source:Virology, Volume 519 Author(s): Pingchao Li, Fengling Feng, Enxiang Pan, Xiaozhen Fan, Qing Yang, Min Guan, Ling Chen, Caijun Sun Adenovirus serotype 5 (Ad5) is a common cause of respiratory tract infection, and populations worldwide have high prevalence of anti-Ad5 antibodies, implying extensively prior infection. Ad5 infection potently activates the host innate defense and inflammation, but the molecular mechanisms are not completely clarified. We report here that monocytes from Ad5-seropositive subjects upregulates the expression of scavenger receptor A (SR-A), and the increased SR-A promote the susceptibility of Ad5 entry and subsequent innate signaling activation. SR-A is also known as major receptor for lipid uptake, we therefore observed that monocytes from Ad5-seropositive subjects accumulated the acetylated low-density lipoprotein (acLDL) and had the elevated cellular stress to induce the activation of monocyte/macrophages. These findings demonstrate that SR-A-mediated Ad5 entry, innate signaling activation and acLDL accumulation synergistically trigger the robust antiviral innate and inflammatory responses, which are helpful to our understanding of the pathogenesis of adenovirus infection.
June 2018
Macaque homologs of Kaposi's sarcoma-associated herpesvirus (KSHV) infect germinal center lymphoid cells, epithelial cells in skin and gastrointestinal tract and gonadal germ cells in naturally infected macaques
Publication date: June 2018
Source:Virology, Volume 519 Author(s): Helle Bielefeldt-Ohmann, A. Gregory Bruce, Kellie Howard, Minako Ikoma, Margaret E. Thouless, Timothy M. Rose We developed a set of rabbit antisera to characterize infections by the macaque RV2 rhadinovirus homologs of KSHV. We analyzed tissues from rhesus and pig-tailed macaques naturally infected with rhesus rhadinovirus (RRV) or Macaca nemestrina rhadinovirus 2 (MneRV2). Our study demonstrates that RV2 rhadinoviruses have a tropism for epithelial cells, lymphocytes and gonadal germ cells in vivo. We observed latent infections in both undifferentiated and differentiated epithelial cells with expression of the latency marker, LANA. Expression of the early (ORF59) and late (glycoprotein B) lytic markers were detected in highly differentiated cells in epithelial ducts in oral, renal, dermal and gastric mucosal tissue as well as differentiated germ cells in male and female gonads. Our data provides evidence that epithelial and germ cell differentiation in vivo induces rhadinovirus reactivation and suggests that infected epithelial and germ cells play a role in transmission and dissemination of RV2 rhadinovirus infections in vivo.
May 2018
Towards quality and order in human papillomavirus research
Publication date: June 2018
Source:Virology, Volume 519 Author(s): Laila Sara Arroyo M
May 2018
Lessons learned from research and surveillance directed at highly pathogenic influenza A viruses in wild birds inhabiting North America
Publication date: May 2018
Source:Virology, Volume 518 Author(s): Andrew M. Ramey, Thomas J. DeLiberto, Yohannes Berhane, David E. Swayne, David E. Stallknecht Following detections of highly pathogenic (HP) influenza A viruses (IAVs) in wild birds inhabiting East Asia after the turn of the millennium, the intensity of sampling of wild birds for IAVs increased throughout much of North America. The objectives for many research and surveillance efforts were directed towards detecting Eurasian origin HP IAVs and understanding the potential of such viruses to be maintained and dispersed by wild birds. In this review, we highlight five important lessons learned from research and surveillance directed at HP IAVs in wild birds inhabiting North America: (1) Wild birds may disperse IAVs between North America and adjacent regions via migration, (2) HP IAVs can be introduced to wild birds in North America, (3) HP IAVs may cross the wild bird-poultry interface in North America, (4) The probability of encountering and detecting a specific virus may be low, and (5) Population immunity of wild birds may influence HP IAV outbreaks in North America. We review empirical support derived from research and surveillance efforts for each lesson learned and, furthermore, identify implications for future surveillance efforts, biosecurity, and population health. We conclude our review by identifying five additional areas in which we think future mechanistic research relative to IAVs in wild birds in North America are likely to lead to other important lessons learned in the years ahead.
May 2018
Seneca Valley Virus 3Cpro abrogates the IRF3- and IRF7-mediated innate immune response by degrading IRF3 and IRF7
Publication date: May 2018
Source:Virology, Volume 518 Author(s): Qiao Xue, Huisheng Liu, Zixiang Zhu, Fan Yang, Linna Ma, Xuepeng Cai, Qinghong Xue, Haixue Zheng Seneca Valley Virus (SVV) is a newly emerged virus belonging to the family Picornaviridae. Basic knowledge of the immunological response to SVV is limited. To date, one study has demonstrated that SVV 3Cpro mediates the cleavage of host MAVS, TRIF, and TANK at specific sites and consequently escapes the host's antiviral innate immunity. In this study, we show that SVV 3Cpro reduces IRF3 and IRF7 protein expression level and phosphorylation. SVV infection also reduces expression of IRF3 and IRF7 protein. The degradation of IRF3 and IRF7 is dependent on the 3Cpro protease activity. We also identify interactions between 3Cpro and IRF3 and IRF7 in PK-15 cells. A detailed analysis revealed that the degradation of IRF3 and IRF7 blocks the transcription of IFN-
May 2018
Expression of the cervical carcinoma expressed PCNA regulatory (CCEPR) long noncoding RNA is driven by the human papillomavirus E6 protein and modulates cell proliferation independent of PCNA
Publication date: May 2018
Source:Virology, Volume 518 Author(s): Surendra Sharma, Karl Munger Modulation of expression of noncoding RNAs is an important aspect of the oncogenic activities of high-risk human papillomavirus (HPV) E6 and E7 proteins. While HPV E6/E7-mediated alterations of microRNAs (miRNAs) has been studied in detail there are fewer reports on HPV-mediated dysregulation of long noncoding RNAs (lncRNAs). The cervical carcinoma expressed PCNA regulatory (CCEPR) lncRNA is highly expressed in cervical cancers and expression correlates with tumor size and patient outcome. We report that CCEPR is a nuclear lncRNA and that HPV16 E6 oncogene expression causes increased CCEPR expression through a mechanism that is not directly dependent on TP53 inactivation. CCEPR depletion in cervical carcinoma cell lines reduces viability, while overexpression enhances viability. In contrast to what was published and inspired its designation, there is no evidence for PCNA mRNA stabilization, and hence CCEPR likely functions through a different mechanism.
May 2018
Evidence for contemporary plant mitoviruses
Publication date: May 2018
Source:Virology, Volume 518 Author(s): Max L. Nibert, Minh Vong, Karen K. Fugate, Humberto J. Debat Mitoviruses have small RNA(+) genomes, replicate in mitochondria, and have been shown to infect only fungi to date. For this report, sequences that appear to represent nearly complete plant mitovirus genomes were recovered from publicly available transcriptome data. Twenty of the refined sequences, 26842898 nt long and derived from 10 different species of land plants, appear to encompass the complete coding regions of contemporary plant mitoviruses, which furthermore constitute a monophyletic cluster within genus Mitovirus. Complete coding sequences of several of these viruses were recovered from multiple transcriptome (but not genome) studies of the same plant species and also from multiple plant tissues. Crop plants among implicated hosts include beet and hemp. Other new results suggest that such genuine plant mitoviruses were immediate ancestors to endogenized mitovirus elements now widespread in land plant genomes. Whether these mitoviruses are wholly cryptic with regard to plant health remains to be investigated.
May 2018
Biological properties of Beet soil-borne mosaic virus and Beet necrotic yellow vein virus cDNA clones produced by isothermal in vitro recombination: Insights for reassortant appearance
Publication date: May 2018
Source:Virology, Volume 518 Author(s): Marlene Laufer, Hamza Mohammad, Edgar Maiss, Katja Richert-P
May 2018
Mammarenaviruses deleted from their Z gene are replicative and produce an infectious progeny in BHK-21 cells
Publication date: May 2018
Source:Virology, Volume 518 Author(s): Am
May 2018
Antigenic and genetic evolution of contemporary swine H1 influenza viruses in the United States
Publication date: May 2018
Source:Virology, Volume 518 Author(s): Daniela S. Rajao, Tavis K. Anderson, Pravina Kitikoon, Jered Stratton, Nicola S. Lewis, Amy L. Vincent Several lineages of influenza A viruses (IAV) currently circulate in North American pigs. Genetic diversity is further increased by transmission of IAV between swine and humans and subsequent evolution. Here, we characterized the genetic and antigenic evolution of contemporary swine H1N1 and H1N2 viruses representing clusters H1-
May 2018
An alanine residue in human parainfluenza virus type 3 phosphoprotein is critical for restricting excessive N0-P interaction and maintaining N solubility
Publication date: May 2018
Source:Virology, Volume 518 Author(s): Shengwei Zhang, Qi Cheng, Chenxi Luo, Lei Yin, Yali Qin, Mingzhou Chen The phosphoprotein (P) of human parainfluenza virus type 3 (HPIV3) plays a pivotal role in viral RNA synthesis, which interacts with the nucleoprotein (N) to form a soluble N0-P complex (N0, free of RNAs) to prevent the nonspecific RNA binding and illegitimate aggregation of N. Functional regions within P have been studied intensively. However, the precise site (s) within P directly involved in N0-P interaction still remains unclear. In this study, using a series of deleted and truncated mutants of P of HPIV3, we demonstrate that amino-terminal 40 amino acids (aa) of P restrict and regulate N0-P interaction. Furthermore, using in vivo HPIV3 minigenome replicon assay, we identify a critical P mutant (PA28P) located in amino-terminal 40 aa, which fails to support RNA synthesis of HPIV3 minigenome replicon. Although PA28P maintains an enhanced N-P interaction, it is unable to form N0-P complex and keep N soluble, thus, resulting in aggregation and functional abolishment of N-P complex. Moreover, we found that recombinant HPIV3 with mutation of A28P in P failed to be rescued. Taken together, we identified a residue within the extreme amino-terminus of P, which plays a critical role in restricting the excessively N-P interaction and keeping a functional N0-P complex formation.
May 2018
The dynamics of both filamentous and globular mammalian reovirus viral factories rely on the microtubule network
Publication date: May 2018
Source:Virology, Volume 518 Author(s): Catherine Eichwald, Mathias Ackermann, Max L. Nibert Mammalian reovirus viral factories (VFs) form filamentous or globular structures depending on the viral strain. In this study, we attempt to characterize the dynamics of both filamentous and globular VFs. Here, we present evidence demonstrating that globular VFs are dynamic entities coalescing between them, thereby gaining in size and concomitantly decreasing in numbers during the course of the infection. Additionally, both kinds of VFs condense into a perinuclear position. Our results show that globular VFs rely on an intact MT-network for dynamic motion, structural assembly, and maintenance and for perinuclear condensation. Interestingly, dynein localizes in both kinds of VFs, having a role at least in large globular VFs formation. To study filamentous VF dynamics, we used different transfection ratios of NS with filamentous 2. We found a MT-network dependency for VF-like structures perinuclear condensation. Also, NS promotes VFLSs perinuclear positioning as well as an increase in acetylated tubulin levels.
May 2018
Foot-and-mouth disease virus type O specific mutations determine RNA-dependent RNA polymerase fidelity and virus attenuation
Publication date: May 2018
Source:Virology, Volume 518 Author(s): Chen Li, Haiwei Wang, Tiangang Yuan, Andrew Woodman, Decheng Yang, Guohui Zhou, Craig E. Cameron, Li Yu Previous studies have shown that the FMDV Asia1/YS/CHA/05 high-fidelity mutagen-resistant variants are attenuated (Zeng et al., 2014). Here, we introduced the same single or multiple-amino-acid substitutions responsible for increased 3Dpol fidelity of type Asia1 FMDV into the type O FMDV O/YS/CHA/05 infectious clone. The rescued viruses O-DA and O-DAMM are lower replication fidelity mutants and showed an attenuated phenotype. These results demonstrated that the same amino acid substitution of 3Dpol in different serotypes of FMDV strains had different effects on viral fidelity. In addition, nucleoside analogues were used to select high-fidelity mutagen-resistant type O FMDV variants. The rescued mutagen-resistant type O FMDV high-fidelity variants exhibited significantly attenuated fitness and a reduced virulence phenotype. These results have important implications for understanding the molecular mechanism of FMDV evolution and pathogenicity, especially in developing a safer modified live-attenuated vaccine against FMDV.
May 2018
AAV8 virions hijack serum proteins to increase hepatocyte binding for transduction enhancement
Publication date: May 2018
Source:Virology, Volume 518 Author(s): Xiaolei Pei, Ting He, Nikita E. Hall, David Gerber, R. Jude Samulski, Chengwen Li It has been demonstrated that human serum albumin (HSA) directly interacts with AAV virions and enhances AAV transduction. Several other proteins have also been identified a potential for enhancing AAV8 liver transduction. In our study, LDL or transferrin could enhance transduction in vitro and in vivo. We also found that any combination of two or three of these proteins (HSA, LDL, and transferrin) increased AAV8 transduction in Huh7 cells and in mice liver, which was similar to albumin alone. Pre-incubation of HSA with AAV8 virions prevented AAV8 virions from binding to other proteins. Furthermore, these serum protein receptors didnt impact AAV8 transduction but blocked the transduction enhancement from AAV8-serum protein complexes. These results indicate that serum proteins are hijacked by AAV8 vectors to increase hepatocyte binding, which shares same binding site. Importantly, the results could help us design an optimal formulation for effective AAV vector delivery in future clinical trials.
May 2018
The human T-cell leukemia virus type-1 p30II protein activates p53 and induces the TIGAR and suppresses oncogene-induced oxidative stress during viral carcinogenesis
Publication date: May 2018
Source:Virology, Volume 518 Author(s): Megan Romeo, Tetiana Hutchison, Aditi Malu, Averi White, Janice Kim, Rachel Gardner, Katie Smith, Katherine Nelson, Rachel Bergeson, Ryan McKee, Carolyn Harrod, Lee Ratner, Bernhard L
May 2018
Comprehensive virome analysis reveals the complexity and diversity of the viral spectrum in pediatric patients diagnosed with severe and mild hand-foot-and-mouth disease
Publication date: May 2018
Source:Virology, Volume 518 Author(s): Chunhua Wang, Shuaifeng Zhou, Wanhua Xue, Liang Shen, Wei Huang, Yi Zhang, Xuguang Li, Junzhi Wang, Hong Zhang, Xuejun Ma The management of hand-foot-and-mouth disease(HFMD) epidemic is difficult due to the frequent emergence of non-EV71 and non-CVA16 enteroviruses and some cases testing negative for HFMD-associated causative agents. To clarify the virus spectrum of mild and severe HFMD, a comprehensive virome analysis of 238 samples was performed using next-generation sequencing (NGS). The data revealed total thirteen mammalian- and plant- virus families and diverse viral populations including enteroviruses, common respiratory viruses, diarrhea-related viruses, plant viruses and anelloviruses. A total of 18 viruses from 7 virus families were identified in severe cases, versus 37 viruses from 12 virus families in mild cases. Moreover, complicated mixed-infections of enteroviruses with common respiratory viruses were mainly found in severe cases(P
May 2018
NDV entry into dendritic cells through macropinocytosis and suppression of T lymphocyte proliferation
Publication date: May 2018
Source:Virology, Volume 518 Author(s): Lei Tan, Yuqiang Zhang, Changtao Qiao, Yanmei Yuan, Yingjie Sun, Xusheng Qiu, Chunchun Meng, Cuiping Song, Ying Liao, Muhammad Munir, Venugopal Nair, Zhuang Ding, Xiufan Liu, Chan Ding Newcastle disease virus (NDV) causes major economic losses in the poultry industry. Previous studies have shown that NDV utilizes different pathways to infect various cells, including dendritic cells (DCs). Here, we demonstrate that NDV gains entry into DCs mainly via macropinocytosis and clathrin-mediated endocytosis. The detection of cytokines interferon-
May 2018
Systemic antibodies administered by passive immunization prevent generalization of the infection by foot-and-mouth disease virus in cattle after oronasal challenge
Publication date: May 2018
Source:Virology, Volume 518 Author(s): Florencia Barrionuevo, Sebasti
May 2018
Octapartite negative-sense RNA genome of High Plains wheat mosaic virus encodes two suppressors of RNA silencing
Publication date: May 2018
Source:Virology, Volume 518 Author(s): Adarsh K. Gupta, Gary L. Hein, Robert A. Graybosch, Satyanarayana Tatineni High Plains wheat mosaic virus (HPWMoV, genus Emaravirus; family Fimoviridae), transmitted by the wheat curl mite (Aceria tosichella Keifer), harbors a monocistronic octapartite single-stranded negative-sense RNA genome. In this study, putative proteins encoded by HPWMoV genomic RNAs 28 were screened for potential RNA silencing suppression activity by using a green fluorescent protein-based reporter agroinfiltration assay. We found that proteins encoded by RNAs 7 (P7) and 8 (P8) suppressed silencing induced by single- or double-stranded RNAs and efficiently suppressed the transitive pathway of RNA silencing. Additionally, a Wheat streak mosaic virus (WSMV, genus Tritimovirus; family Potyviridae) mutant lacking the suppressor of RNA silencing (
May 2018
Networks of protein-protein interactions among structural proteins of budded virus of Bombyx mori nucleopolyhedrovirus
Publication date: May 2018
Source:Virology, Volume 518 Author(s): Jianjia Zhang, Min Feng, Ying Fan, Weifan Xu, Qin Zheng, Xiaofeng Wu The structural proteins of baculovirus are well studied, but the interactions between them remain unclear. In order to reveal protein-protein interactions among viral structural proteins and their associated proteins of the budded virus of Bombyx mori nucleopolyhedrovirus (BmNPV), the yeast two hybrid (Y2H) system was used to evaluate the interactions of 27 viral genes products. Fifty-seven interactions were identified with 51 binary interactions and 6 self-associations. Among them, 10 interactions were further confirmed by co-immunoprecipitation assays. Five interaction networks were formed based on the direct-cross Y2H assays. VP39, 38
May 2018
Porcine reproductive and respiratory syndrome virus induces HMGB1 secretion via activating PKC-delta to trigger inflammatory response
Publication date: May 2018
Source:Virology, Volume 518 Author(s): Rong Wang, Liping Yang, Yali Zhang, Junyan Li, Liran Xu, Yueqiang Xiao, Qian Zhang, Liang Bai, Sihai Zhao, Enqi Liu, Yan-Jin Zhang Porcine reproductive and respiratory syndrome virus (PRRSV) causes inflammatory injuries in infected pigs. PRRSV induces secretion of high mobility group box 1 (HMGB1) that enhances inflammatory response. However, the mechanism of PRRSV-induced HMGB1 secretion is unknown. Here, we discovered PRRSV induced HMGB1 secretion via activating protein kinase C-delta (PKC
May 2018
Differential phosphorylation and n-terminal configuration of capsid subunits in parvovirus assembly and viral trafficking
Publication date: May 2018
Source:Virology, Volume 518 Author(s): Jon Gil-Ranedo, Eva Hernando, Noelia Valle, Laura Riolobos, Beatriz Maroto, Jos
May 2018
Characterization of H9N2 avian influenza viruses from the Middle East demonstrates heterogeneity at amino acid position 226 in the hemagglutinin and potential for transmission to mammals
Publication date: May 2018
Source:Virology, Volume 518 Author(s): Klaudia Chrzastek, Dong-hun Lee, Saad Gharaibeh, Aniko Zsak, Darrell R. Kapczynski Next-generation sequencing (NGS) technologies are a valuable tool to monitor changes in viral genomes and determine the genetic heterogeneity of viruses. In this study, NGS was applied to clinical poultry samples from Jordan to detect eleven H9N2 low pathogenic avian influenza viruses (LPAIV). All of the viruses tested belonged to Middle East A genetic group of G1 lineage. Deep sequencing demonstrated a high degree of heterogeneity of glutamine and leucine residues at position 226 in the hemagglutinin (HA) gene, which increases specificity to either avian or mammalian-type receptors. Moreover, additional amino acid changes in PB1, PA, M1, M2, and NS1 were identified among the viruses tested. Compared to single gene amplification, application of NGS for surveillance and characterization of H9N2 LPAIV provides a complete genetic profile of emerging isolates and better understanding of the potential of zoonotic transmissions to mammals.
May 2018
Cellular Hsp27 interacts with classical swine fever virus NS5A protein and negatively regulates viral replication by the NF-
May 2018
Enhancement of safety and immunogenicity of the Chinese Hu191 measles virus vaccine by alteration of the S-adenosylmethionine (SAM) binding site in the large polymerase protein
Publication date: May 2018
Source:Virology, Volume 518 Author(s): Yilong Wang, Rongxian Liu, Mijia Lu, Yingzhi Yang, Duo Zhou, Xiaoqiang Hao, Dongming Zhou, Bin Wang, Jianrong Li, Yao-Wei Huang, Zhengyan Zhao The live-attenuated measles virus (MV) vaccine based on the Hu191 strain has played a significant role in controlling measles in China. However, it has considerable adverse effects that may cause public health burden. We hypothesize that the safety and efficacy of MV vaccine can be improved by altering the S-adenosylmethionine (SAM) binding site in the conserved region VI of the large polymerase protein. To test this hypothesis, we established an efficient reverse genetics system for the rMV-Hu191 strain and generated two recombinant MV-Hu191 carrying mutations in the SAM binding site. These two mutants grew to high titer in Vero cells, were genetically stable, and were significantly more attenuated in vitro and in vivo compared to the parental rMV-Hu191 vaccine strain. Importantly, both MV-Hu191 mutants triggered a higher neutralizing antibody than rMV-Hu191 vaccine and provided complete protection against MV challenge. These results demonstrate its potential for an improved MV vaccine candidate.
May 2018
Serotype-specific restriction of wild-type adenoviruses by the cellular Mre11-Rad50-Nbs1 complex
Publication date: May 2018
Source:Virology, Volume 518 Author(s): Neha J. Pancholi, Matthew D. Weitzman During viral replication in the nucleus, the DNA genomes of adenoviruses are accessible to cellular DNA-binding proteins. Human adenovirus type 5 (Ad5) targets the cellular Mre11-Rad50-Nbs1 complex (MRN) to evade detection by the DNA damage response (DDR). Ad5 mutants that cannot target MRN have reduced viral propagation. Previous studies showed that diverse adenovirus serotypes interact differently with MRN. While these studies revealed diverse MRN interactions among serotypes, it remains unclear how these differences influence viral replication. Here, we examined effects of the DDR on several adenovirus serotypes. We demonstrate that wild-type Ad9 and Ad12 do not overcome MRN impairment. We also examined viral proteins involved in targeting MRN and found that unlike Ad5-E4orf3, expression of Ad9-E4orf3 is not sufficient for MRN mislocalization observed during infection. We conclude that adenovirus serotypes target MRN in distinct ways, and the MRN complex can impair DNA replication of wild-type viruses across the adenovirus family.
May 2018
Evidence for a novel negative-stranded RNA mycovirus isolated from the plant pathogenic fungus Fusarium graminearum
Publication date: May 2018
Source:Virology, Volume 518 Author(s): Luan Wang, Hao He, Shuangchao Wang, Xiaoguang Chen, Dewen Qiu, Hideki Kondo, Lihua Guo Here we describe a novel (
May 2018
Tat controls transcriptional persistence of unintegrated HIV genome in primary human macrophages
Publication date: May 2018
Source:Virology, Volume 518 Author(s): Beatrix Meltzer, Deemah Dabbagh, Jia Guo, Fatah Kashanchi, Mudit Tyagi, Yuntao Wu In HIV infected macrophages, a large population of viral genomes persists as the unintegrated form (uDNA) that is transcriptionally active. However, how this transcriptional activity is controlled remains unclear. In this report, we investigated whether Tat, the viral transactivator of transcription, is involved in uDNA transcription. We demonstrate that de novo Tat activity is generated from uDNA, and this uDNA-derived Tat (uTat) transactivates the uDNA LTR. In addition, uTat is required for the transcriptional persistence of uDNA that is assembled into repressive episomal minichromatin. In the absence of uTat, uDNA minichromatin is gradually silenced, but remains highly inducible by HDAC inhibitors (HDACi). Therefore, functionally, uTat antagonizes uDNA minichromatin repression to maintain persistent viral transcription in macrophages. uTat-mediated viral persistence may establish a viral reservoir in macrophages where uDNA were found to persist.
May 2018
Identification of nucleotides in the 5UTR and amino acids substitutions that are essential for the infectivity of 5UTR-NS5A recombinant of hepatitis C virus genotype 1b (strain Con1)
Publication date: May 2018
Source:Virology, Volume 518 Author(s): Jinqian Li, Shengjun Feng, Xi Liu, Mingzhe Guo, Mingxiao Chen, Yiyi Chen, Liang Rong, Jinyu Xia, Yuanping Zhou, Jin Zhong, Yi-Ping Li Genotype 1b strain Con1 represents an important reference in the study of hepatitis C virus (HCV). Here, we aimed to develop an advanced infectious Con1 recombinant. We found that previously identified mutations A1226G/F1464L/A1672S/Q1773H permitted culture adaption of Con1 Core-NS5A (C-5A) recombinant containing 5UTR and NS5B-3UTR from JFH1 (genotype 2a), thus acquired additional mutations L725H/F886L/D2415G. C-5A containing all seven mutations (C-5A_7m) replicated efficiently in Huh7.5 and Huh7.5.1 cells and had an increased infectivity in SEC14L2-expressing Huh7.5.1 cells. Incorporation of Con1 NS5B was deleterious to C-5A_7m, however Con1 5UTR was permissive but attenuated the virus. Nucleotides G1, A4, and G35 primarily accounted for the viral attenuation without affecting RNA translation. C-5A_7m was inhibited dose-dependently by simeprevir and daclatasvir, and substitutions at A4, A29, A34, and G35 conferred resistance to miR-122 antagonism. The novel Con1 5UTR-NS5A recombinant, adaptive mutations, and critical nucleotides described here will facilitate future studies of HCV culture systems and virus-host interaction.
May 2018
Lipid biosensor interactions with wild type and matrix deletion HIV-1 Gag proteins
Publication date: May 2018
Source:Virology, Volume 518 Author(s): Eric Barklis, August O. Staubus, Andrew Mack, Logan Harper, Robin Lid Barklis, Ayna Alfadhli The matrix (MA) domain of the HIV-1 precursor Gag protein (PrGag) has been shown interact with the HIV-1 envelope (Env) protein, and to direct PrGag proteins to plasma membrane (PM) assembly sites by virtue of its affinity to phosphatidylinositol-4,5-bisphosphate (PI[4,5]P2). Unexpectedly, HIV-1 viruses with large MA deletions (
May 2018
Hexon and fiber of adenovirus type 14 and 55 are major targets of neutralizing antibody but only fiber-specific antibody contributes to cross-neutralizing activity
Publication date: May 2018
Source:Virology, Volume 518 Author(s): Ying Feng, Xikui Sun, Xianmiao Ye, Yupeng Feng, Jinlin Wang, Xuehua Zheng, Xinglong Liu, Changhua Yi, Mingli Hao, Qian Wang, Feng Li, Wei Xu, Liang Li, Chufang Li, Rong Zhou, Ling Chen, Liqiang Feng Re-emerging human adenoviruses type 14 (HAdV14) and 55 (HAdV55) represent two highly virulent adenoviruses. The neutralizing antibody (nAb) responses elicited by infection or immunization remain largely unknown. Herein, we generated hexon-chimeric HAdV14 viruses harboring each single or entire hexon hyper-variable-regions (HVR) from HAdV55, and determined the neutralizing epitopes of human and mouse nAbs. In human sera, hexon-targeting nAbs are type-specific and mainly recognize HVR2, 5, and 7. Fiber-targeting nAbs are only detectable in sera cross-neutralizing HAdV14 and HAdV55 and contribute substantially to cross-neutralization. Penton-binding antibodies, however, show no significant neutralizing activities. In mice immunized with HAdV14 or HAdV55, a single immunization mainly elicited hexon-specific nAbs, which recognized HAdV14 HVR1, 2, and 7 and HAdV55 HVR1 and 2, respectively. After a booster immunization, cross-neutralizing fiber-specific nAbs became detectable. These results indicated that hexon elicits type-specific nAbs whereas fiber induces cross-neutralizing nAbs to HAdV14 and HAdV55, which are of significance in vaccine development.
May 2018
Characterization of murine antibody responses to vaccinia virus envelope protein A14 reveals an immunodominant antigen lacking of effective neutralization targets
Publication date: May 2018
Source:Virology, Volume 518 Author(s): Xiangzhi Meng, Thomas Kaever, Bo Yan, Paula Traktman, Dirk M. Zajonc, Bjoern Peters, Shane Crotty, Yan Xiang Vaccinia virus (VACV) A14 is a major envelope protein and a dominant antibody target in the smallpox vaccine. However, the role of anti-A14 antibodies in immunity against orthopoxviruses is unclear. Here, we characterized 22 A14 monoclonal antibodies (mAb) from two mice immunized with VACV. Epitope mapping showed that 21 mAbs targeted the C-terminal hydrophilic region, while one mAb recognized the middle region predicted to be across the viral envelope from the C-terminus. However, none of the mAbs bound to virions in studies with electron microscopy. Interestingly, some mAbs showed low VACV neutralization activities in the presence of complement and provided protection to SCID mice challenged with VACV ACAM2000. Our data showed that, although A14 is an immunodominant antigen in smallpox vaccine, its B cell epitopes are either enclosed within the virions or are inaccessible on virion surface. Anti-A14 antibodies, however, could contribute to protection against VACV through a complement-dependent pathway.

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May 2018
Extending the hosts of Tectiviridae into four additional genera of Gram-positive bacteria and more diverse Bacillus species
Publication date: May 2018
Source:Virology, Volume 518 Author(s): Matti Jalasvuori, Katariina Koskinen Tectiviridae are composed of tailless bacteriophages with an icosahedral capsid and an inner membrane enclosing a double-stranded 15
May 2018
MARCH2 is upregulated in HIV-1 infection and inhibits HIV-1 production through envelope protein translocation or degradation
Publication date: May 2018
Source:Virology, Volume 518 Author(s): You Zhang, Jing Lu, Xinqi Liu MARCH2 is one of the MARCH family E3 ligases, which contains eleven members that play pivotal roles in controlling the turn-over of membrane proteins, such as MHC class I, MHC class II, and cell surface receptors. In this study, we found the expression of MARCH2 to be upregulated upon HIV-1 infection. MARCH2 inhibits the production and infection of HIV-1 through ligase activity-dependent envelope protein degradation and/or intracellular retention, a mechanism shared by MARCH8 that also leads to the inhibition of HIV-1 infection. Nevertheless, unlike MARCH8 and other MARCH proteins whose transcription levels are unrelated to viral infection, the expression level of MARCH2 is markedly upregulated upon HIV-1 infection, conferring MARCH2 a unique role in monitoring and regulating the HIV-1 infection-associated process.
May 2018
Infection by Zika viruses requires the transmembrane protein AXL, endocytosis and low pH
Publication date: May 2018
Source:Virology, Volume 518 Author(s): Mirjana Persaud, Alicia Martinez-Lopez, Cindy Buffone, Steven A. Porcelli, Felipe Diaz-Griffero The recent Zika virus (ZIKV) outbreak in Brazil has suggested associations of this virus infection with neurological disorders, including microcephaly in newborn infants and Guillian-Barr
May 2018
Broadly protective anti-hemagglutinin stalk antibodies induced by live attenuated influenza vaccine expressing chimeric hemagglutinin
Publication date: May 2018
Source:Virology, Volume 518 Author(s): Irina Isakova-Sivak, Daniil Korenkov, Tatiana Smolonogina, Tatiana Kotomina, Svetlana Donina, Victoria Matyushenko, Daria Mezhenskaya, Florian Krammer, Larisa Rudenko The development of influenza vaccines that can provide broad protection against all drifted seasonal virus variants, zoonotic infections and emerging pandemic strains, has been a priority for two decades. Here we propose a strategy of inducing broadly-reactive anti-stalk antibody by sequential immunizations with live attenuated influenza vaccines (LAIVs) expressing chimeric HAs (cHAs). These vaccines are designed to contain identical hemagglutinin stalk domains from H1N1 virus but antigenically unrelated globular head domains from avian influenza virus subtypes H5, H8 and H9. Mouse experiments demonstrated enhanced cross-protection of cHA-containing LAIVs compared to the relevant vaccine viruses expressing natural HAs, and this enhanced protection was driven by stalk-HA-reactive IgG antibodies. The establishment of fully functional cross-protective immunity after two doses of cHA LAIV vaccination in na
May 2018
An emerging and expanding clade accounts for the persistent outbreak of Coxsackievirus A6-associated hand, foot, and mouth disease in China since 2013
Publication date: May 2018
Source:Virology, Volume 518 Author(s): Shuizhen He, Mengyuan Chen, Wenhui Wu, Qiang Yan, Zhihao Zhuo, Xiaosong Su, Shiyin Zhang, Shengxiang Ge, Ningshao Xia Enterovirus (EV)-A71 and Coxsackievirus (CV)-A16 have historically been the major pathogens of hand, foot, and mouth disease (HMFD) in China; however, CV-A6
May 2018
Ectromelia virus lacking the E3L ortholog is replication-defective and nonpathogenic but does induce protective immunity in a mouse strain susceptible to lethal mousepox
Publication date: May 2018
Source:Virology, Volume 518 Author(s): Tiffany R. Frey, Katherine S. Forsyth, Maura M. Sheehan, Brian C. De Haven, Julia G. Pevarnik, Erin S. Hand, Marie C. Pizzorno, Laurence C. Eisenlohr, Adam R. Hersperger All known orthopoxviruses, including ectromelia virus (ECTV), contain a gene in the E3L family. The protein product of this gene, E3, is a double-stranded RNA-binding protein. It can impact host range and is used by orthopoxviruses to combat cellular defense pathways, such as PKR and RNase L. In this work, we constructed an ECTV mutant with a targeted disruption of the E3L open reading frame (ECTV
May 2018
Reduction of soluble dipeptidyl peptidase 4 levels in plasma of patients infected with Middle East respiratory syndrome coronavirus
Publication date: May 2018
Source:Virology, Volume 518 Author(s): Kyung-Soo Inn, Yuri Kim, Abdimadiyeva Aigerim, Uni Park, Eung-Soo Hwang, Myung-Sik Choi, Yeon-Sook Kim, Nam-Hyuk Cho Dipeptidyl peptidase 4 (DPP4) is a receptor for MERS-CoV. The soluble form of DPP4 (sDPP4) circulates systematically and can competitively inhibit MERS-CoV entry into host cells. Here, we measured the concentration of sDPP4 in the plasma and sputa of 14 MERS-CoV-infected patients of various degrees of disease severity. The concentration of sDPP4 in the plasma of MERS patients (474.76
May 2018
Transcriptional Analysis of the Guinea Pig Mucosal Immune Response to Intravaginal Infection with Herpes Simplex Virus Type 2
Publication date: May 2018
Source:Virology, Volume 518 Author(s): Ronald L. Veselenak, Gregg N. Milligan, Aaron L. Miller, Richard B. Pyles, Nigel Bourne Genital herpes infection in guinea pigs closely models human infection but tools for immune characterization are limited. Immunity to HSV infection at the vaginal epithelial surface was characterized in guinea pigs using PCR-based array analysis of vaginal swab samples. IFN

Impact of immune escape mutations and N-linked glycosylation on the secretion of hepatitis B virus virions and subviral particles: Role of the small envelope protein
Publication date: May 2018
Source:Virology, Volume 518 Author(s): Xiaohui Bi, Shuping Tong Hepatitis B virus (HBV) expresses three co-terminal envelope proteins: large (L), middle (M), and small (S), with the S protein driving the secretion of both virions and subviral particles. Virion secretion requires N-linked glycosylation at N146 in the S domain but can be impaired by immune escape mutations. An M133T mutation creating a novel glycosylation site at N131could rescue virion secretion of N146Q mutant (loss of original glycosylation site) and immune escape mutants such as G145R. Here we demonstrate that other novel N-linked glycosylation sites could rescue virion secretion of the G145R and N146Q mutants to variable extents. Both G145R and N146Q mutations impaired virion secretion through the S protein. The M133T mutation restored virion secretion through the S protein, and could work in trans. Impaired virion secretion was not necessarily associated with a similar block in the secretion of subviral particles.
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