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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
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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
#9
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
#10
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
#11
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
#12
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
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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