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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
#1
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
#2
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 22, 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
#3
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
#4
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
#5
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
https://www.readbyqxmd.com/read/28148803/m-gene-reassortment-in-h9n2-influenza-virus-promotes-early-infection-and-replication-contribution-to-rising-virus-prevalence-in-chickens-in-china
#6
Juan Pu, Honglei Sun, Yi Qu, Chenxi Wang, Weihua Gao, Junda Zhu, Yipeng Sun, Yuhai Bi, Yinhua Huang, Kin-Chow Chang, Jie Cui, Jinhua Liu
Segment reassortment and base mutagenesis of influenza A viruses are the primary routes to the rapid evolution of high-fitness virus genotypes. We recently described a predominant G57 genotype of avian H9N2 viruses that caused countrywide outbreaks in chickens in China during 2010 to 2013, which led to the zoonotic emergence of H7N9 viruses. One of the key features of the G57 genotype is the replacement of the earlier A/chicken/Beijing/1/1994 (BJ/94)-like M gene with the A/quail/Hong Kong/G1/1997 (G1)-like M gene of quail origin...
April 15, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28141843/zika-virus-tissue-and-blood-compartmentalization-in-acute-infection-of-rhesus-macaques
#7
Lark L Coffey, Patricia A Pesavento, Rebekah I Keesler, Anil Singapuri, Jennifer Watanabe, Rie Watanabe, JoAnn Yee, Eliza Bliss-Moreau, Christina Cruzen, Kari L Christe, J Rachel Reader, Wilhelm von Morgenland, Anne M Gibbons, A Mark Allen, Jeff Linnen, Kui Gao, Eric Delwart, Graham Simmons, Mars Stone, Marion Lanteri, Sonia Bakkour, Michael Busch, John Morrison, Koen K A Van Rompay
Animal models of Zika virus (ZIKV) are needed to better understand tropism and pathogenesis and to test candidate vaccines and therapies to curtail the pandemic. Humans and rhesus macaques possess similar fetal development and placental biology that is not shared between humans and rodents. We inoculated 2 non-pregnant rhesus macaques with a 2015 Brazilian ZIKV strain. Consistent with most human infections, the animals experienced no clinical disease but developed short-lived plasma viremias that cleared as neutralizing antibody developed...
2017: PloS One
https://www.readbyqxmd.com/read/28126917/an-in-vitro-fluorescence-based-study-of-initiation-of-rna-synthesis-by-influenza-b-polymerase
#8
Stefan Reich, Delphine Guilligay, Stephen Cusack
Influenza polymerase replicates, via a complementary RNA intermediate (cRNA), and transcribes the eight viral RNA (vRNA) genome segments. To initiate RNA synthesis it is bound to the conserved 5΄ and 3΄ extremities of the vRNA or cRNA (the 'promoter'). 5΄-3΄ base-pairing in the distal promoter region is essential to position the template RNA at the polymerase active site, as shown by a new crystal structure with the 3΄ end threading through the template entry tunnel. We develop fluorescence polarization assays to quantify initiation of cap-primed (transcription) or unprimed (replication) RNA synthesis by recombinant influenza B polymerase bound to the vRNA or cRNA promoter...
April 7, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28115197/structural-insights-into-rna-synthesis-by-the-influenza-virus-transcription-replication-machine
#9
REVIEW
Alexander Pflug, Maria Lukarska, Patricia Resa-Infante, Stefan Reich, Stephen Cusack
Influenza virus is a segmented, negative strand RNA virus with each genome segment being packaged in a distinct ribonucleoprotein particle (RNP). The RNP consists of the heterotrimeric viral RNA-dependent RNA polymerase bound to the conserved 5' and 3' ends of the genome segment (the viral promoter) with the rest of the viral RNA (vRNA) being covered by multiple copies of nucleoprotein. This review focusses on the new insights that recent crystal structures have given into the detailed molecular mechanisms by which the polymerase performs both transcription and replication of the vRNA genome...
January 20, 2017: Virus Research
https://www.readbyqxmd.com/read/28054965/attacked-from-all-sides-rna-decay-in-antiviral-defense
#10
REVIEW
Jerome M Molleston, Sara Cherry
The innate immune system has evolved a number of sensors that recognize viral RNA (vRNA) to restrict infection, yet the full spectrum of host-encoded RNA binding proteins that target these foreign RNAs is still unknown. The RNA decay machinery, which uses exonucleases to degrade aberrant RNAs largely from the 5' or 3' end, is increasingly recognized as playing an important role in antiviral defense. The 5' degradation pathway can directly target viral messenger RNA (mRNA) for degradation, as well as indirectly attenuate replication by limiting specific pools of endogenous RNAs...
January 4, 2017: Viruses
https://www.readbyqxmd.com/read/28002402/structural-basis-of-an-essential-interaction-between-influenza-polymerase-and-pol-ii-ctd
#11
Maria Lukarska, Guillaume Fournier, Alexander Pflug, Patricia Resa-Infante, Stefan Reich, Nadia Naffakh, Stephen Cusack
The heterotrimeric influenza polymerase (FluPol), comprising subunits PA, PB1 and PB2, binds to the conserved 5' and 3' termini (the 'promoter') of each of the eight single-stranded viral RNA (vRNA) genome segments and performs both transcription and replication of vRNA in the infected cell nucleus. To transcribe viral mRNAs, FluPol associates with cellular RNA polymerase II (Pol II), which enables it to take 5'-capped primers from nascent Pol II transcripts. Here we present a co-crystal structure of bat influenza A polymerase bound to a Pol II C-terminal domain (CTD) peptide mimic, which shows two distinct phosphoserine-5 (SeP5)-binding sites in the polymerase PA subunit, accommodating four CTD heptad repeats overall...
January 5, 2017: Nature
https://www.readbyqxmd.com/read/27999393/diverse-strategies-used-by-picornaviruses-to-escape-host-rna-decay-pathways
#12
REVIEW
Wendy Ullmer, Bert L Semler
To successfully replicate, viruses protect their genomic material from degradation by the host cell. RNA viruses must contend with numerous destabilizing host cell processes including mRNA decay pathways and viral RNA (vRNA) degradation resulting from the antiviral response. Members of the Picornaviridae family of small RNA viruses have evolved numerous diverse strategies to evade RNA decay, including incorporation of stabilizing elements into vRNA and re-purposing host stability factors. Viral proteins are deployed to disrupt and inhibit components of the decay machinery and to redirect decay machinery to the advantage of the virus...
December 20, 2016: Viruses
https://www.readbyqxmd.com/read/27910909/the-disinfection-characteristics-of-ebola-virus-outbreak-variants
#13
Bradley W M Cook, Todd A Cutts, Aidan M Nikiforuk, Anders Leung, Darwyn Kobasa, Steven S Theriault
The recent Ebola virus outbreak in West Africa has forced experts to re-evaluate their understanding of how to best disinfect areas contaminated with infectious bodily fluids. Recent research has found that Ebola virus remains viable in blood for 7-10 days making appropriate disinfection crucial to infection control. We sought to determine if the three most important outbreak variants of Zaire ebolavirus (Mayinga, Kikwit and Makona) exhibit separate phenotypes when challenged with a range of sodium hypochlorite (NaOCl) concentrations or 70% ethanol (EtOH) at average West African temperature...
December 2, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27903277/sequence-diversity-of-dengue-virus-type-2-in-brain-and-thymus-of-infected-interferon-receptor-ko-mice-implications-for-dengue-virulence
#14
Priya Dhole, Emi E Nakayama, Akatsuki Saito, Kriengsak Limkittikul, Supranee Phanthanawiboon, Tatsuo Shioda, Takeshi Kurosu
BACKGROUND: We previously reported that a clinical isolate of dengue virus (DENV) is capable of causing acute-phase systemic infection in mice harboring knockouts of the genes encoding type-I and -II interferon IFN receptors (IFN-α/β/γR KO mice); in contrast, other virulent DENV isolates exhibited slow disease progression in this mice, yielding lethal infection around 20 days post-infection (p.i.). In the present study, we sought to clarify the dynamics of slow disease progression by examining disease progression of a type-2 DENV clinical isolate (DV2P04/08) in mice...
November 30, 2016: Virology Journal
https://www.readbyqxmd.com/read/27889648/pb2-substitutions-v598t-i-increase-the-virulence-of-h7n9-influenza-a-virus-in-mammals
#15
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...
January 15, 2017: Virology
https://www.readbyqxmd.com/read/27886255/amino-acid-substitutions-v63i-or-a37s-i61t-v63i-v100a-in-the-pa-n-terminal-domain-increase-the-virulence-of-h7n7-influenza-a-virus
#16
Meng Hu, Hin Chu, Ke Zhang, Kailash Singh, Cun Li, Shuofeng Yuan, Billy K C Chow, Wenjun Song, Jie Zhou, Bo-Jian Zheng
The PA N-terminal domain (PA-Nter) is essential for viral transcription and replication. Here we identified PA-Nter substitutions A37S, I61T, V63I and V100A in recently emerged avian influenza A viruses (IAVs) with potential effect on virus pathogenicity and/or host adaptation. We introduced the identified PA-Nter substitutions into avian H7N7 IAV by reverse genetics. Our results showed that single substitution V63I and combined substitutions, I61T/V63I and A37S/I61T/V63I/V100A (Mfour), significantly increased virus growth capacity in mammalian cells...
November 25, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27852861/pre-mrna-processing-factor-prp18-is-a-stimulatory-factor-of-influenza-virus-rna-synthesis-and-possesses-nucleoprotein-chaperone-activity
#17
M Minakuchi, K Sugiyama, Y Kato, T Naito, M Okuwaki, A Kawaguchi, K Nagata
The genome of influenza virus (viral RNA [vRNA]) is associated with the nucleoprotein (NP) and viral RNA-dependent RNA polymerases and forms helical viral ribonucleoprotein (vRNP) complexes. The NP-vRNA complex is the biologically active template for RNA synthesis by the viral polymerase. Previously, we identified human pre-mRNA processing factor 18 (Prp18) as a stimulatory factor for viral RNA synthesis using a Saccharomyces cerevisiae replicon system and a single-gene deletion library of Saccharomyces cerevisiae (T...
February 1, 2017: Journal of Virology
https://www.readbyqxmd.com/read/27766900/pathogenicity-tissue-distribution-shedding-and-environmental-detection-of-two-strains-of-ibdv-following-infection-of-chickens-at-0-and-14-days-of-age
#18
J M K G K Jayasundara, S W Walkden-Brown, M E Katz, A F M F Islam, K G Renz, J McNally, P W Hunt
Infectious bursal disease virus (IBDV) is endemic to most poultry-producing countries worldwide. Immunosuppressive classical and variant IBDV strains endemic to Australia are genetically distinct from other international strains. We report the results of infection experiments with Australian classical strain 06/95 and variant strain 02/95 in SPF chickens. We tested the effects of strain and age of infection on bursal atrophy, viral RNA (vRNA) load in bursa of Fabricius (bursa), spleen, thymus, caecal tonsils, faeces, litter and exhaust dust as determined by real-time reverse transcriptase polymerase chain reaction...
June 2017: Avian Pathology: Journal of the W.V.P.A
https://www.readbyqxmd.com/read/27741407/moving-on-out-transport-and-packaging-of-influenza-viral-rna-into-virions
#19
Seema S Lakdawala, Ervin Fodor, Kanta Subbarao
Influenza A viruses bear an eight-segmented single-stranded negative-sense RNA genome that is replicated in the nucleus. Newly synthesized viral RNA (vRNA) segments are exported from the nucleus and transported to the plasma membrane for packaging into progeny virions. Influenza viruses exploit many host proteins during these events, and this is the portion of the viral life cycle when genetic reassortment among influenza viruses occurs. Reassortment among influenza A viruses allows viruses to expand their host range, virulence, and pandemic potential...
September 29, 2016: Annual Review of Virology
https://www.readbyqxmd.com/read/27733686/targeting-a-novel-rna-protein-interaction-for-therapeutic-intervention-of-hantavirus-disease
#20
Nilshad N Salim, Safder S Ganaie, Anuradha Roy, Subbiah Jeeva, Mohammad A Mir
An evolutionarily conserved sequence at the 5' terminus of hantaviral genomic RNA plays an important role in viral transcription initiation and packaging of the viral genome into viral nucleocapsids. Interaction of viral nucleocapsid protein (N) with this conserved sequence facilitates mRNA translation by a unique N-mediated translation strategy. Whereas this evolutionarily conserved sequence facilitates virus replication with the assistance of N in eukaryotic hosts having multifaceted antiviral defense, we demonstrate its interaction with N presents a novel target for therapeutic intervention of hantavirus disease...
November 18, 2016: Journal of Biological Chemistry
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