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https://www.readbyqxmd.com/read/28922369/crimean-congo-hemorrhagic-fever-virus-nucleocapsid-protein-has-dual-rna-binding-modes
#1
Subbiah Jeeva, Sean Pador, Brittany Voss, Safder Saieed Ganaie, Mohammad Ayoub Mir
Crimean Congo hemorrhagic fever, a zoonotic viral disease, has high mortality rate in humans. There is currently no vaccine for Crimean Congo hemorrhagic fever virus (CCHFV) and chemical interventions are limited. The three negative sense genomic RNA segments of CCHFV are specifically encapsidated by the nucleocapsid protein into three ribonucleocapsids, which serve as templates for the viral RNA dependent RNA polymerase. Here we demonstrate that CCHFV nucleocapsid protein has two distinct binding modes for double and single strand RNA...
2017: PloS One
https://www.readbyqxmd.com/read/28911100/genome-wide-analysis-of-influenza-viral-rna-and-nucleoprotein-association
#2
Nara Lee, Valerie Le Sage, Adalena V Nanni, Dan J Snyder, Vaughn S Cooper, Seema S Lakdawala
Influenza A virus (IAV) genomes are composed of eight single-stranded RNA segments that are coated by viral nucleoprotein (NP) molecules. Classically, the interaction between NP and viral RNA (vRNA) is depicted as a uniform pattern of 'beads on a string'. Using high-throughput sequencing of RNA isolated by crosslinking immunoprecipitation (HITS-CLIP), we identified the vRNA binding profiles of NP for two H1N1 IAV strains in virions. Contrary to the prevailing model for vRNA packaging, NP does not bind vRNA uniformly in the A/WSN/1933 and A/California/07/2009 strains, but instead each vRNA segment exhibits a unique binding profile, containing sites that are enriched or poor in NP association...
September 6, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28910636/epitranscriptomic-enhancement-of-influenza-a-virus-gene-expression-and-replication
#3
David G Courtney, Edward M Kennedy, Rebekah E Dumm, Hal P Bogerd, Kevin Tsai, Nicholas S Heaton, Bryan R Cullen
Many viral RNAs are modified by methylation of the N(6) position of adenosine (m(6)A). m(6)A is thought to regulate RNA splicing, stability, translation, and secondary structure. Influenza A virus (IAV) expresses m(6)A-modified RNAs, but the effects of m(6)A on this segmented RNA virus remain unclear. We demonstrate that global inhibition of m(6)A addition inhibits IAV gene expression and replication. In contrast, overexpression of the cellular m(6)A "reader" protein YTHDF2 increases IAV gene expression and replication...
September 13, 2017: Cell Host & Microbe
https://www.readbyqxmd.com/read/28878087/novel-stable-ebola-virus-minigenome-replicon-reveals-remarkable-stability-of-the-viral-genome
#4
Wanyin Tao, Tianyu Gan, Mingzhe Guo, Yongfen Xu, Jin Zhong
Ebola virus (EBOV) causes severe hemorrhagic fever in humans and other primates with a high case fatality rate. No approved drug or vaccine of EBOV is available, which necessitates better understanding of the virus life cycle. Studies on EBOV have been hampered because experimentations involving live virus are restricted to biosafety level 4 (BSL-4) laboratories. EBOV minigenome system has provided researchers with the opportunity to study EBOV under BSL-2 conditions. Here, we developed a novel EBOV minigenome replicon which, to our knowledge, is the first EBOV cell culture system that can stably replicate and transcribe EBOV minigenome...
September 6, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28859270/effect-of-the-fourth-nucleotide-at-the-3-end-of-neuraminidase-and-matrix-viral-genomic-rna-on-the-pathogenicity-of-influenza-virus-a-pr-8-34
#5
Chung-Young Lee, Hyuk-Joon Kwon, Thanh Trung Nguyen, Ilhwan Kim, Hyung-Kwan Jang, Jae-Hong Kim
Twelve nucleotides located at the 3' end of viral genomic RNA (vRNA) are conserved among influenza A viruses (IAV) and have a promoter function. Hoffmann's 8-plasmid reverse genetics vector system introduced mutations at position 4, C nucleotide (C4) to U nucleotide (U4), of the 3' ends of neuraminidase (NA) and matrix (M) vRNAs of wild-type A/PR/8/34 (PR8). This resulted in a constellation of C4 and U4 vRNAs coding for low (polymerases) and relatively high (all others) copy number proteins, respectively. U4 has been reported to increase promoter activity in comparison to C4, but the constellation effect on the replication efficiency and pathogenicity of reverse genetics PR8 (rgPR8) has not been fully elucidated...
August 31, 2017: Journal of Veterinary Science
https://www.readbyqxmd.com/read/28794024/highly-pathogenic-new-world-arenavirus-infection-activates-the-pattern-recognition-receptor-pkr-without-attenuating-virus-replication-in-human-cells
#6
Cheng Huang, Olga A Kolokoltsova, Elizabeth J Mateer, Takaaki Koma, Slobodan Paessler
The arenavirus family consists of several highly pathogenic viruses including the Old World (OW) arenavirus Lassa fever virus (LASV) and the New World (NW) Junín virus (JUNV) and Machupo virus (MACV). Host response to infection by these pathogenic arenaviruses is distinct in many aspects. NW JUNV and MACV infections readily induce an IFN response in human cells, while OW LASV infection usually triggers an undetectable or weak IFN response. JUNV induces IFN response through RIG-I, suggesting that the host non-self RNA sensor readily detects JUNV viral RNAs during infection and activates IFN response...
August 9, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28768860/zinc-finger-containing-cellular-transcription-corepressor-zbtb25-promotes-influenza-virus-rna-transcription-and-is-a-target-for-zinc-ejector-drugs
#7
Shu-Chuan Chen, King-Song Jeng, Michael M C Lai
Influenza A virus (IAV) replication relies on an intricate interaction between virus and host cells. How the cellular proteins are usurped for IAV replication remains largely obscure. The aim of this study was to search for novel and potential cellular factors that participate in IAV replication. ZBTB25, a transcription repressor of a variety of cellular genes, was identified by an RNAi genomic library screening. Depletion of ZBTB25 significantly reduced IAV production. Conversely, overexpression of ZBTB25 enhanced it...
August 2, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28746373/zika-virus-preferentially-replicates-in-the-female-reproductive-tract-after-vaginal-inoculation-of-rhesus-macaques
#8
Timothy Carroll, Ming Lo, Marion Lanteri, Joseph Dutra, Katie Zarbock, Paola Silveira, Tracy Rourke, Zhong-Min Ma, Linda Fritts, Shelby O'Connor, Michael Busch, Christopher J Miller
Zika virus (ZIKV) is a mosquito-transmitted virus that can cause severe defects in an infected fetus. ZIKV is also transmitted by sexual contact, although the relative importance of sexual transmission is unclear. To better understand the role of sexual transmission in ZIKV pathogenesis, a nonhuman primate (NHP) model of vaginal transmission was developed. ZIKV was readily transmitted to mature cycling female rhesus macaque (RM) by vaginal inoculation with 104-106 plaque-forming units (PFU). However, there was variability in susceptibility between the individual RM with 1->8 vaginal inoculations required to establish infection...
July 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28732035/vaccine-induced-immune-responses-against-both-gag-and-env-improve-control-of-simian-immunodeficiency-virus-replication-in-rectally-challenged-rhesus-macaques
#9
Mauricio A Martins, Young C Shin, Lucas Gonzalez-Nieto, Aline Domingues, Martin J Gutman, Helen S Maxwell, Iris Castro, Diogo M Magnani, Michael Ricciardi, Nuria Pedreño-Lopez, Varian Bailey, Dillon Betancourt, John D Altman, Matthias Pauthner, Dennis R Burton, Benjamin von Bredow, David T Evans, Maoli Yuan, Christopher L Parks, Keisuke Ejima, David B Allison, Eva Rakasz, Glen N Barber, Saverio Capuano, Jeffrey D Lifson, Ronald C Desrosiers, David I Watkins
The ability to control lentivirus replication may be determined, in part, by the extent to which individual viral proteins are targeted by the immune system. Consequently, defining the antigens that elicit the most protective immune responses may facilitate the design of effective HIV-1 vaccines. Here we vaccinated four groups of rhesus macaques with a heterologous vector prime/boost/boost/boost (PBBB) regimen expressing the following simian immunodeficiency virus (SIV) genes: env, gag, vif, rev, tat, and nef (Group 1); env, vif, rev, tat, and nef (Group 2); gag, vif, rev, tat, and nef (Group 3); or vif, rev, tat, and nef (Group 4)...
July 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28724771/intracellular-colocalization-of-influenza-viral-rna-and-rab11a-is-dependent-upon-microtubule-filaments
#10
Eric Nturibi, Amar R Bhagwat, Stefanie Coburn, Mike M Myerburg, Seema S Lakdawala
Influenza A virus (IAV) consists of eight viral RNA (vRNA) segments that are replicated in the host cell nucleus and transported to the plasma membrane for packaging into progeny virions. We have previously proposed a model where sub-complexes of vRNA export from the nucleus and assemble en route to the plasma membrane. However, the role of host cytoskeletal proteins in the cytoplasmic assembly of IAV vRNA segments remains unknown. Previous studies have suggested that IAV vRNA segments transport via Rab11A-containing recycling endosomes (RE) and use both microtubules (MT) and actin...
July 19, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28709400/broad-range-potential-of-asphodelus-microcarpus-leaves-extract-for-drug-development
#11
Amalia Di Petrillo, Antonella Fais, Francesca Pintus, Celestino Santos-Buelga, Ana M González-Paramás, Vincenzo Piras, Germano Orrù, Antonello Mameli, Enzo Tramontano, Aldo Frau
BACKGROUND: Many plants have been used in traditional medicine for their antibacterial, antifungal, antiprotozoal, antiviral, antidiarrhoeal, analgesic, antimalarial, antioxidant, anti-inflammatory and anticancer activities. In order to find novel antimicrobial and antiviral agents, the aim of the present study was the evaluation of the antibacterial and antibiofilm susceptibility of Asphodelus microcarpus leaves extract. Moreover, the antiviral activity and the phytochemical composition of the active extract were also determined...
July 14, 2017: BMC Microbiology
https://www.readbyqxmd.com/read/28690069/bovine-leukemia-virus-g4-enhances-virus-production
#12
Hironobu Murakami, Shotaro Asano, Jumpei Uchiyama, Reiichiro Sato, Masahiro Sakaguchi, Kenji Tsukamoto
The nonstructural G4 gene of bovine leukemia virus (BLV) has been thought to function in virus replication. However, the discovery of the AS1 gene on the antisense strand of the G4 gene has affected this interpretation. In this study, we investigated the function of G4 in virus production independent of the AS1 gene using a reverse genetic approach, and briefly examined the association of the G4 protein with Tax, which is also a nonstructural protein that promotes virus replication. First, we constructed a mutant molecular clone of BLV with a nonsense mutation in G4 that had a minimal effect on the AS1 gene...
July 6, 2017: Virus Research
https://www.readbyqxmd.com/read/28662365/a-compensatory-mutagenesis-study-of-a-conserved-hairpin-in-the-m-gene-segment-of-influenza-a-virus-shows-its-role-in-virus-replication
#13
M I Spronken, C E van de Sandt, E P de Jongh, O Vuong, S van der Vliet, T M Bestebroer, R C L Olsthoorn, G F Rimmelzwaan, R A M Fouchier, A P Gultyaev
RNA structures are increasingly recognized to be of importance during influenza A virus replication. Here, we investigated a predicted conserved hairpin in the M gene segment (nt 967-994) within the region of the vRNA 5' packaging signal. The existence of this RNA structure and its possible role in virus replication was investigated using a compensatory mutagenesis approach. Mutations were introduced in the hairpin stem, based on natural variation. Virus replication properties were studied for the mutant viruses with disrupted and restored RNA structures...
June 29, 2017: RNA Biology
https://www.readbyqxmd.com/read/28662211/identification-of-interactions-between-sindbis-virus-capsid-protein-and-cytoplasmic-vrna-as-novel-virulence-determinants
#14
Kevin J Sokoloski, Lauren M Nease, Nicholas A May, Natasha N Gebhart, Claire E Jones, Thomas E Morrison, Richard W Hardy
Alphaviruses are arthropod-borne viruses that represent a significant threat to public health at a global level. While the formation of alphaviral nucleocapsid cores, consisting of cargo nucleic acid and the viral capsid protein, is an essential molecular process of infection, the precise interactions between the two partners are ill-defined. A CLIP-seq approach was used to screen for candidate sites of interaction between the viral Capsid protein and genomic RNA of Sindbis virus (SINV), a model alphavirus...
June 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28557173/a-fluorescent-rna-forced-intercalation-probe-as-a-pan-selective-marker-for-influenza%C3%A2-a-virus-infection
#15
Ivan Haralampiev, Matthias Schade, Jasmine Chamiolo, Fabian Jolmes, Simon Prisner, Peter T Witkowski, Marie Behrent, Felix Hövelmann, Thorsten Wolff, Oliver Seitz, Andreas Herrmann
The influenza A virus (IAV) genome is segmented into eight viral ribonucleoproteins, each expressing a negatively oriented viral RNA (vRNA). Along the infection cycle, highly abundant single-stranded small viral RNAs (svRNA) are transcribed in a segment-specific manner. The sequences of svRNAs and of the vRNA 5'-ends are identical and highly conserved among all IAV strains. Here, we demonstrate that these sequences can be used as a target for a pan-selective sensor of IAV infection. To this end, we used a complementary fluorescent forced-intercalation RNA (IAV QB-FIT) probe with a single locked nucleic acid substitution to increase brightness...
August 17, 2017: Chembiochem: a European Journal of Chemical Biology
https://www.readbyqxmd.com/read/28542550/a-spatio-temporal-assessment-of-simian-human-immunodeficiency-virus-shiv-evolution-reveals-a-highly-dynamic-process-within-the-host
#16
Alison F Feder, Christopher Kline, Patricia Polacino, Mackenzie Cottrell, Angela D M Kashuba, Brandon F Keele, Shiu-Lok Hu, Dmitri A Petrov, Pleuni S Pennings, Zandrea Ambrose
The process by which drug-resistant HIV-1 arises and spreads spatially within an infected individual is poorly understood. Studies have found variable results relating how HIV-1 in the blood differs from virus sampled in tissues, offering conflicting findings about whether HIV-1 throughout the body is homogeneously distributed. However, most of these studies sample only two compartments and few have data from multiple time points. To directly measure how drug resistance spreads within a host and to assess how spatial structure impacts its emergence, we examined serial sequences from four macaques infected with RT-SHIVmne027, a simian immunodeficiency virus encoding HIV-1 reverse transcriptase (RT), and treated with RT inhibitors...
May 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28530165/basic-amino-acids-in-the-n-terminal-half-of-the-pb2-subunit-of-influenza-virus-rna-polymerase-are-involved-in-both-transcription-and-replication
#17
Koyu Hara, Takahito Kashiwagi, Nobuyuki Hamada, Hiroshi Watanabe
The PB2 subunit of influenza virus RNA polymerase is known to be involved in the initiation of transcription of the virus genome via cap binding. However, other specific roles of PB2 for viral RNA synthesis are not well understood. Here, we demonstrate that basic residues, 124R, 142R, 143R, 268R and 331K/332R, in the N-terminal half of PB2 are important for the polymerase activity. Notably, R124A mutation remarkably reduced the synthesis of mRNA, cRNA and vRNA in vivo, which was in good agreement with the data obtained in vitro...
May 2017: Journal of General Virology
https://www.readbyqxmd.com/read/28472156/genetically-barcoded-siv-facilitates-enumeration-of-rebound-variants-and-estimation-of-reactivation-rates-in-nonhuman-primates-following-interruption-of-suppressive-antiretroviral-therapy
#18
Christine M Fennessey, Mykola Pinkevych, Taina T Immonen, Arnold Reynaldi, Vanessa Venturi, Priyanka Nadella, Carolyn Reid, Laura Newman, Leslie Lipkey, Kelli Oswald, William J Bosche, Matthew T Trivett, Claes Ohlen, David E Ott, Jacob D Estes, Gregory Q Del Prete, Jeffrey D Lifson, Miles P Davenport, Brandon F Keele
HIV and SIV infection dynamics are commonly investigated by measuring plasma viral loads. However, this total viral load value represents the sum of many individual infection events, which are difficult to independently track using conventional sequencing approaches. To overcome this challenge, we generated a genetically tagged virus stock (SIVmac239M) with a 34-base genetic barcode inserted between the vpx and vpr accessory genes of the infectious molecular clone SIVmac239. Next-generation sequencing of the virus stock identified at least 9,336 individual barcodes, or clonotypes, with an average genetic distance of 7 bases between any two barcodes...
May 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28384338/peripheral-and-central-immune-cell-reservoirs-in-tissues-from-asymptomatic-cats-chronically-infected-with-feline-immunodeficiency-virus
#19
C D Eckstrand, E E Sparger, K A Pitt, B G Murphy
Feline immunodeficiency virus (FIV) infection in cats results in life-long viral persistence and progressive immunopathology. We have previously described a cohort of experimentally infected cats demonstrating a progressive decline of peripheral blood CD4+ T-cell over six years in the face of apparent peripheral viral latency. More recently we reported findings from this same cohort that revealed popliteal lymph node tissue as sites for ongoing viral replication suggesting that tissue reservoirs are important in FIV immunopathogenesis during the late asymptomatic phase of infection...
2017: PloS One
https://www.readbyqxmd.com/read/28248290/systems-based-analysis-of-rig-i-dependent-signalling-identifies-khsrp-as-an-inhibitor-of-rig-i-receptor-activation
#20
Stephen Soonthornvacharin, Ariel Rodriguez-Frandsen, Yingyao Zhou, Felipe Galvez, Nicholas J Huffmaster, Shashank Tripathi, Vinod R M T Balasubramaniam, Atsushi Inoue, Elisa de Castro, Hong Moulton, David A Stein, María Teresa Sánchez-Aparicio, Paul D De Jesus, Quy Nguyen, Renate König, Nevan J Krogan, Adolfo García-Sastre, Sunnie M Yoh, Sumit K Chanda
Retinoic acid-inducible gene I (RIG-I) receptor recognizes 5'-triphosphorylated RNA and triggers a signalling cascade that results in the induction of type-I interferon (IFN)-dependent responses. Its precise regulation represents a pivotal balance between antiviral defences and autoimmunity. To elucidate the cellular cofactors that regulate RIG-I signalling, we performed two global RNA interference analyses to identify both positive and negative regulatory nodes operating on the signalling pathway during virus infection...
March 1, 2017: Nature Microbiology
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