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Virology

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https://www.readbyqxmd.com/read/28628829/ectromelia-virus-accumulates-less-double-stranded-rna-compared-to-vaccinia-virus-in-bs-c-1-cells
#1
Tiffany R Frey, Michael H Lehmann, Colton M Ryan, Marie C Pizzorno, Gerd Sutter, Adam R Hersperger
Most orthopoxviruses, including vaccinia virus (VACV), contain genes in the E3L and K3L families. The protein products of these genes have been shown to combat PKR, a host defense pathway. Interestingly, ectromelia virus (ECTV) contains an E3L ortholog but does not possess an intact K3L gene. Here, we gained insight into how ECTV can still efficiently evade PKR despite lacking K3L. Relative to VACV, we found that ECTV-infected BS-C-1 cells accumulated considerably less double-stranded (ds) RNA, which was due to lower mRNA levels and less transcriptional read-through of some genes by ECTV...
June 16, 2017: Virology
https://www.readbyqxmd.com/read/28628828/sensitivity-to-bst-2-restriction-correlates-with-orthobunyavirus-host-range
#2
Mariana Varela, Ilaria M Piras, Catrina Mullan, Xiaohong Shi, Natasha L Tilston-Lunel, Rute Maria Pinto, Aislynn Taggart, Stephen R Welch, Stuart J D Neil, Felix Kreher, Richard M Elliott, Massimo Palmarini
Orthobunyaviruses include several recently emerging viruses of significant medical and veterinary importance. There is currently very limited understanding on what determines the host species range of these pathogens. In this study we discovered that BST-2/tetherin restricts orthobunyavirus replication in a host-specific manner. We show that viruses with human tropism (Oropouche virus and La Crosse virus) are restricted by sheep BST-2 but not by the human orthologue, while viruses with ruminant tropism (Schmallenberg virus and others) are restricted by human BST-2 but not by the sheep orthologue...
June 16, 2017: Virology
https://www.readbyqxmd.com/read/28628827/evolutionary-conservation-of-influenza-a-pb2-sequences-reveals-potential-target-sites-for-small-molecule-inhibitors
#3
Hershna Patel, Andreas Kukol
The influenza A basic polymerase protein 2 (PB2) functions as part of a heterotrimer to replicate the viral RNA genome. To investigate novel PB2 antiviral target sites, this work identified evolutionary conserved regions across the PB2 protein sequence amongst all sub-types and hosts, as well as ligand binding hot spots which overlap with highly conserved areas. Fifteen binding sites were predicted in different PB2 domains; some of which reside in areas of unknown function. Virtual screening of ~50,000 drug-like compounds showed binding affinities of up to -10...
June 16, 2017: Virology
https://www.readbyqxmd.com/read/28625407/xenopus-fv3-host-pathogen-interactions-and-immune-evasion
#4
Robert Jacques, Eva-Stina Edholm, Sanchez Jazz, Torres-Luquis Odalys, De Jesús Andino Francisco
We first review fundamental insights into anti-ranavirus immunity learned with the Xenopus laevis/ranavirus FV3 model that are generally applicable to ectothermic vertebrates. We then further investigate FV3 genes involved in immune evasion. Focusing on FV3 knockout (KO) mutants defective for a putative viral caspase activation and recruitment domain-containing (CARD)-like protein (Δ64R-FV3), a β-hydroxysteroid dehydrogenase homolog (Δ52L-FV3), and an immediate-early18kDa protein (FV3-Δ18K), we assessed the involvement of these viral genes in replication, dissemination and interaction with peritoneal macrophages in tadpole and adult frogs...
June 15, 2017: Virology
https://www.readbyqxmd.com/read/28624679/neuraminidase-based-recombinant-virus-like-particles-protect-against-lethal-avian-influenza-a-h5n1-virus-infection-in-ferrets
#5
Gale E Smith, Xiangjie Sun, Yaohui Bai, Ye V Liu, Michael J Massare, Melissa B Pearce, Jessica A Belser, Taronna R Maines, Hannah M Creager, Gregory M Glenn, David Flyer, Peter Pushko, Min Z Levine, Terrence M Tumpey
Avian influenza A (H5N1) viruses represent a growing threat for an influenza pandemic. The presence of widespread avian influenza virus infections further emphasizes the need for vaccine strategies for control of pre-pandemic H5N1 and other avian influenza subtypes. Influenza neuraminidase (NA) vaccines represent a potential strategy for improving vaccines against avian influenza H5N1 viruses. To evaluate a strategy for NA vaccination, we generated a recombinant influenza virus-like particle (VLP) vaccine comprised of the NA protein of A/Indonesia/05/2005 (H5N1) virus...
June 15, 2017: Virology
https://www.readbyqxmd.com/read/28622575/protein-nanoparticle-vaccine-based-on-flagellin-carrier-fused-to-influenza-conserved-epitopes-confers-full-protection-against-influenza-a-virus-challenge
#6
Lei Deng, Jong R Kim, Timothy Z Chang, Han Zhang, Teena Mohan, Julie A Champion, Bao-Zhong Wang
Currently marketed influenza vaccines only confer protection against matching influenza virus strains. The influenza A composition of these vaccines needs to be annually updated. Vaccines that target conserved epitopes of influenza viruses would in principle offer broad cross-protection against influenza A viruses. In our study, we investigated the specific immune responses and protective efficacy of protein nanoparticles based on fusion proteins of flagellin carrier linked to conserved influenza epitopes. We designed fusion proteins by replacing the hyperimmunogenic region of flagellin (FliC) with four tandem copies of the ectodomain of matrix protein 2 (f4M2e), H1 HA2 domain (fHApr8) or H3 HA2 domain (fHAaichi)...
June 13, 2017: Virology
https://www.readbyqxmd.com/read/28618303/transcriptomic-response-of-the-insect-vector-peregrinus-maidis-to-maize-mosaic-rhabdovirus-and-identification-of-conserved-responses-to-propagative-viruses-in-hopper-vectors
#7
Kathleen M Martin, Karen Barandoc-Alviar, Derek J Schneweis, Catherine L Stewart, Dorith Rotenberg, Anna E Whitfield
Maize mosaic virus (MMV) is a plant-pathogenic rhabdovirus that is transmitted by the corn planthopper, Peregrinus maidis, in a propagative manner. P. maidis supports long-term MMV infections with no negative effects on insect performance. To elucidate whole-body transcriptome responses to virus infection, RNA-Seq was used to examine differential gene expression of virus-infected adult insects, and libraries were prepared from replicated groups of virus-exposed insects and non-exposed insects. From the 68,003 de novo-assembled transcripts, 144 were differentially-expressed (DE) during viral infection with comparable numbers up- and down-regulated...
June 12, 2017: Virology
https://www.readbyqxmd.com/read/28605637/hepatitis-b-surface-antigen-on-subviral-particles-reduces-the-neutralizing-effect-of-anti-hbs-antibodies-on-hepatitis-b-viral-particles-in-vitro
#8
Gustaf E Rydell, Kasthuri Prakash, Heléne Norder, Magnus Lindh
During hepatitis B virus (HBV) infections subviral particles (SVP) consisting mainly of hepatitis B surface antigen are present at much higher concentration than viral particles (VP) in serum. To investigate reasons for this excess of SVP production, SVP and VP were fractionated on a Nycodenz gradient and analyzed for HBV infection of HepG2-NTCP cells with and without anti-HBs antibodies. Our findings showed that SVP significantly reduced the neutralization of VP by anti-HBs, while SVP had little effect on viral entry, supporting the assumption that SVP serve as decoy facilitating cell-to-cell spread of HBV in the presence of neutralizing antibodies...
June 9, 2017: Virology
https://www.readbyqxmd.com/read/28605636/a-sendai-virus-recombinant-vaccine-expressing-a-gene-for-truncated-human-metapneumovirus-hmpv-fusion-protein-protects-cotton-rats-from-hmpv-challenge
#9
Charles J Russell, Bart G Jones, Robert E Sealy, Sherri L Surman, John N Mason, Randall T Hayden, Ralph A Tripp, Toru Takimoto, Julia L Hurwitz
Human metapneumovirus (hMPV) infections pose a serious health risk to young children, particularly in cases of premature birth. No licensed vaccine exists and there is no standard treatment for hMPV infections apart from supportive hospital care. We describe the production of a Sendai virus (SeV) recombinant that carries a gene for a truncated hMPV fusion (F) protein (SeV-MPV-Ft). The vaccine induces binding and neutralizing antibody responses toward hMPV and protection against challenge with hMPV in a cotton rat system...
June 9, 2017: Virology
https://www.readbyqxmd.com/read/28605635/expression-of-herv-k108-envelope-interferes-with-hiv-1-production
#10
Sandra N Terry, Lara Manganaro, Alvaro Cuesta-Dominguez, Daria Brinzevich, Viviana Simon, Lubbertus C F Mulder
The human endogenous retroviruses (HERV)-K of the HML-2 group include full-length or near full-length elements encoding functional proteins, and are classified as type-1 or type-2 (type-1 has a deletion in the 5' end of the env gene). Because proteins of different retroviruses can interact, we hypothesized that HERV-K envelope (Env) could influence HIV-1 replication. Here we describe the negative effect of envelope expression of certain type-2 HERV-Ks on HIV-1 production. All HIV-1 and SIV strains tested were susceptible to various degrees to inhibition by the HERV-K108 envelope...
June 9, 2017: Virology
https://www.readbyqxmd.com/read/28595094/two-plasmid-system-to-increase-the-rescue-efficiency-of-paramyxoviruses-by-reverse-genetics-the-example-of-rescuing-newcastle-disease-virus
#11
Haijin Liu, Emmanuel Albina, Patricia Gil, Cécile Minet, Renata Servan de Almeida
Within paramyxoviruses, conventional reverse genetics require the transfection of a minimum of four plasmids: three to reconstruct the viral polymerase complex that replicates and expresses the virus genome delivered by a fourth plasmid. The successful transfection of four or more plasmids of different sizes into one cell and the subsequent generation of at least one viable and replicable viral particle is a rare event, which explains the low rescue efficiency, especially of low virulent viruses with reduced replication efficiency in cell lines...
June 5, 2017: Virology
https://www.readbyqxmd.com/read/28595093/association-of-polymorphisms-in-key-th-17-immune-response-genes-with-hbeag-positive-chronic-hepatitis-b-susceptibility-and-response-to-peg-ifna-2%C3%AE
#12
Hui Ju, Hua Liu, Zi-Bin Tian, Yue-Ping Jiang, Cui-Ping Zhang, Xi-Shuang Liu
This study aims to investigate effects of polymorphisms in key Th-17 immune response genes on the susceptibility to HBeAg-positive (HBeAg(+)) chronic hepatitis B (CHB) and response to PEG-IFNa-2α. A total of 139 patients with HBeAg(+) CHB treated with PEG-IFNa-2α and 145 healthy controls were enrolled to explore the association between IL-17A, IL-17F, IL-21 and IL-23R polymorphisms and HBeAg(+) CHB susceptibility, as well as treatment efficacies. Genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and DNA sequencing...
June 5, 2017: Virology
https://www.readbyqxmd.com/read/28595092/ebolavirus-protein-vp24-interferes-with-innate-immune-responses-by-inhibiting-interferon-%C3%AE-1-gene-expression
#13
Felix He, Krister Melén, Sari Maljanen, Rickard Lundberg, Miao Jiang, Pamela Österlund, Laura Kakkola, Ilkka Julkunen
Ebolaviruses (EBOV) cause severe disease with a recent outbreak in West Africa in 2014-2015 leading to more than 28 000 cases and 11 300 fatalities. This emphasizes the urgent need for better knowledge on these highly pathogenic RNA viruses. Host innate immune responses play a key role in restricting the spread of a viral disease. In this study we systematically analyzed the effects of cloned EBOV genes on the main host immune response to RNA viruses: the activation of RIG-I pathway and type I and III interferon (IFN) gene expression...
June 5, 2017: Virology
https://www.readbyqxmd.com/read/28586650/e6-proteins-of-%C3%AE-and-%C3%AE-cutaneous-hpv-types-differ-in-their-ability-to-potentiate-wnt-signaling
#14
Sophia Sominsky, Naama Shterzer, Anna Jackman, Beny Shapiro, Abraham Yaniv, Levana Sherman
We recently showed that E6 protein of human papillomavirus (HPV) 16, a mucosal high-risk α-PV type, can potentiate Wnt/β-catenin/TCF signaling. Here we investigated the transcriptional activities of E6 proteins of cutaneous HPV types from the β and α genera. Results from reporter-gene assays showed that similar to HPV16 E6, E6 of HPV10, a cutaneous α-HPV type that is prevalent in skin warts, efficiently enhances and stimulates Wnt/β-catenin/TCF transcription. HPV10 E6 also effectively elevated the expression levels of β-catenin and promoted its nuclear accumulation...
June 3, 2017: Virology
https://www.readbyqxmd.com/read/28577856/glycosylation-and-oligomeric-state-of-envelope-protein-might-influence-hiv-1-virion-capture-by-%C3%AE-4%C3%AE-7-integrin
#15
Subhash Chand, Emily L Messina, Wadad AlSalmi, Neeti Ananthaswamy, Guofen Gao, Gherman Uritskiy, Victor Padilla-Sanchez, Marthandan Mahalingam, Kristina K Peachman, Merlin L Robb, Mangala Rao, Venigalla B Rao
The α4ß7 integrin present on host cells recognizes the V1V2 domain of the HIV-1 envelope protein. This interaction might be involved in virus transmission. Administration of α4ß7-specific antibodies inhibit acquisition of SIV in a macaque challenge model. But the molecular details of V1V2: α4ß7 interaction are unknown and its importance in HIV-1 infection remains controversial. Our biochemical and mutational analyses show that glycosylation is a key modulator of V1V2 conformation and binding to α4ß7...
May 31, 2017: Virology
https://www.readbyqxmd.com/read/28577855/quantitative-analyses-reveal-distinct-sensitivities-of-the-capture-of-hiv-1-primary-viruses-and-pseudoviruses-to-broadly-neutralizing-antibodies
#16
Jiae Kim, Ousman Jobe, Kristina K Peachman, Nelson L Michael, Merlin L Robb, Mangala Rao, Venigalla B Rao
Development of vaccines capable of eliciting broadly neutralizing antibodies (bNAbs) is a key goal to controlling the global AIDS epidemic. To be effective, bNAbs must block the capture of HIV-1 to prevent viral acquisition and establishment of reservoirs. However, the role of bNAbs, particularly during initial exposure of primary viruses to host cells, has not been fully examined. Using a sensitive, quantitative, and high-throughput qRT-PCR assay, we found that primary viruses were captured by host cells and converted into a trypsin-resistant form in less than five minutes...
May 31, 2017: Virology
https://www.readbyqxmd.com/read/28577469/the-interaction-between-hiv-1-nef-and-adaptor-protein-2-reduces-nef-mediated-cd4-t-cell-apoptosis
#17
Rajesh Abraham Jacob, Aaron L Johnson, Emily N Pawlak, Brennan S Dirk, Logan R Van Nynatten, S M Mansour Haeryfar, Jimmy D Dikeakos
Acquired Immune Deficiency Syndrome is characterized by a decline in CD4(+) T cells. Here, we elucidated the mechanism underlying apoptosis in Human Immunodeficiency Virus-1 (HIV-1) infection by examining host apoptotic pathways hijacked by the HIV-1 Nef protein in the CD4(+) T-cell line Sup-T1. Using a panel of Nef mutants unable to bind specific host proteins we uncovered that Nef generates pro- and anti-apoptotic signals. Apoptosis increased upon mutating the motifs involved in the interaction of Nef:AP-1 (NefM20A or NefEEEE62-65AAAA) or Nef:AP-2 (NefLL164/165AA), implying these interactions limit Nef-mediated apoptosis...
May 31, 2017: Virology
https://www.readbyqxmd.com/read/28570919/calcein-represses-human-papillomavirus-16-e1-e2-mediated-dna-replication-via-blocking-their-binding-to-the-viral-origin-of-replication
#18
Dipon Das, Nathan W Smith, Xu Wang, Stacie L Richardson, Matthew C T Hartman, Iain M Morgan
Human papillomaviruses are causative agents in several human diseases ranging from genital warts to ano-genital and oropharyngeal cancers. Currently only symptoms of HPV induced disease are treated; there are no antivirals available that directly target the viral life cycle. Previously, we determined that the cellular protein TopBP1 interacts with the HPV16 replication/transcription factor E2. This E2-TopBP1 interaction is essential for optimal E1-E2 DNA replication and for the viral life cycle. The drug calcein disrupts the interaction of TopBP1 with itself and other host proteins to promote cell death...
May 29, 2017: Virology
https://www.readbyqxmd.com/read/28554059/residues-f103-and-m106-within-the-influenza-a-virus-ns1-cpsf4-binding-region-regulate-interferon-stimulated-gene-translation-initiation
#19
Ben X Wang, Earl G Brown, Eleanor N Fish
Influenza A virus (IAV) non-structural protein 1 (NS1) suppresses host innate immune responses by inhibiting type I interferon (IFN) production. We provide evidence that residues F103 and M106 in the CPSF4-binding domain of A/HK/1/68 [H3N2] NS1 contribute to post-transcriptional inhibition of antiviral IFN-stimulated genes (ISGs), thereby suppressing an antiviral type I IFN response. Recombinant (r) IAVs encoding F103L and M106I mutations in NS1 replicate to significantly lower viral titers in human A549 lung epithelial cells and primary type II alveolar cells...
May 26, 2017: Virology
https://www.readbyqxmd.com/read/28554058/stockpiled-pre-pandemic-h5n1-influenza-virus-vaccines-with-as03-adjuvant-provide-cross-protection-from-h5n2-clade-2-3-4-4-virus-challenge-in-ferrets
#20
Xiangjie Sun, Jessica A Belser, Joanna A Pulit-Penaloza, Hannah M Creager, Zhu Guo, Stacie N Jefferson, Feng Liu, Ian A York, James Stevens, Taronna R Maines, Daniel B Jernigan, Jacqueline M Katz, Min Z Levine, Terrence M Tumpey
Avian influenza viruses, notably H5 subtype viruses, pose a continuous threat to public health due to their pandemic potential. In recent years, influenza virus H5 subtype split vaccines with novel oil-in-water emulsion based adjuvants (e.g. AS03, MF59) have been shown to be safe, immunogenic, and able to induce broad immune responses in clinical trials, providing strong scientific support for vaccine stockpiling. However, whether such vaccines can provide protection from infection with emerging, antigenically distinct clades of H5 viruses has not been adequately addressed...
May 26, 2017: Virology
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