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https://www.readbyqxmd.com/read/28054965/attacked-from-all-sides-rna-decay-in-antiviral-defense
#1
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
#2
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...
December 21, 2016: Nature
https://www.readbyqxmd.com/read/27999393/diverse-strategies-used-by-picornaviruses-to-escape-host-rna-decay-pathways
#3
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
#4
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
#5
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
#6
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
#7
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-the-np-chaperone-activity
#8
M Minakuchi, K Sugiyama, Y Kato, T Naito, M Okuwaki, A Kawaguchi, K Nagata
: The genome of influenza virus (vRNA) is associated with nucleoprotein (NP) and viral RNA-dependent RNA polymerases, and forms helical viral ribonucleoprotein (vRNP) complexes. 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 an yeast replicon system and single-gene deletion library of yeast (Naito T, Kiyasu Y, Sugiyama K, Kimura A, Nakano R, Matsukage A, Nagata K...
November 16, 2016: 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
#9
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...
December 12, 2016: 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
#10
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
#11
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
https://www.readbyqxmd.com/read/27695950/rescue-of-recombinant-newcastle-disease-virus-current-cloning-strategies-and-rna-polymerase-provision-systems
#12
REVIEW
Aidin Molouki, Ben Peeters
Since the first rescue of a recombinant Newcastle disease virus (rNDV) in the late 1990s, many more rNDVs have been rescued by researchers around the world. Regardless of methodology, the main principle behind rescue of the virus has remained the same, i.e., the formation of a functional replication complex by simultaneously providing the full-length viral RNA and the viral NP, P and L proteins. However, different strategies have been reported for the insertion of the full-length genome into a suitable transcription vector, which remains the most challenging step of the rescue...
October 1, 2016: Archives of Virology
https://www.readbyqxmd.com/read/27694620/single-molecule-fret-reveals-the-pre-initiation-and-initiation-conformations-of-influenza-virus-promoter-rna
#13
Nicole C Robb, Aartjan J W Te Velthuis, Ralph Wieneke, Robert Tampé, Thorben Cordes, Ervin Fodor, Achillefs N Kapanidis
Influenza viruses have a segmented viral RNA (vRNA) genome, which is replicated by the viral RNA-dependent RNA polymerase (RNAP). Replication initiates on the vRNA 3' terminus, producing a complementary RNA (cRNA) intermediate, which serves as a template for the synthesis of new vRNA. RNAP structures show the 3' terminus of the vRNA template in a pre-initiation state, bound on the surface of the RNAP rather than in the active site; no information is available on 3' cRNA binding. Here, we have used single-molecule Förster resonance energy transfer (smFRET) to probe the viral RNA conformations that occur during RNAP binding and initial replication...
December 1, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27694388/secondary-structure-model-of-the-naked-segment-7-influenza-a-virus-genomic-rna
#14
Agnieszka Ruszkowska, Elzbieta Lenartowicz, Walter N Moss, Ryszard Kierzek, Elzbieta Kierzek
The influenza A virus genome is comprised of eight negative-sense viral (v)RNA segments. The seventh segment of the genome encodes two essential viral proteins and is specifically packaged alongside the other seven vRNAs. To gain insight into the possible roles of RNA structure both within and without virions, a secondary structure model of a naked (protein-free) segment 7 vRNA has been determined using chemical mapping and thermodynamic energy minimization. The proposed structure model was validated using microarray mapping, RNase H cleavage and comparative sequence analysis...
September 30, 2016: Biochemical Journal
https://www.readbyqxmd.com/read/27692070/viral-rna-switch-mediates-the-dynamic-control-of-flavivirus-replicase-recruitment-by-genome-cyclization
#15
Zhong-Yu Liu, Xiao-Feng Li, Tao Jiang, Yong-Qiang Deng, Qing Ye, Hui Zhao, Jiu-Yang Yu, Cheng-Feng Qin
Viral replicase recruitment and long-range RNA interactions are essential for RNA virus replication, yet the mechanism of their interplay remains elusive. Flaviviruses include numerous important human pathogens, e.g., dengue virus (DENV) and Zika virus (ZIKV). Here, we revealed a highly conserved, conformation-tunable cis-acting element named 5'-UAR-flanking stem (UFS) in the flavivirus genomic 5' terminus. We demonstrated that the UFS was critical for efficient NS5 recruitment and viral RNA synthesis in different flaviviruses...
October 1, 2016: ELife
https://www.readbyqxmd.com/read/27681127/ubiquitination-up-regulates-influenza-virus-polymerase-function
#16
James Kirui, Arindam Mondal, Andrew Mehle
: The influenza A virus polymerase plays an essential role in the virus lifecycle, directing synthesis of viral mRNAs and genomes. It is a trimeric complex composed of subunits PA, PB1, and PB2 and associates with viral RNAs and nucleoprotein (NP) to form higher order ribonucleoprotein (RNP) complexes. The polymerase is regulated temporally over the course of infection to ensure coordinated expression of viral genes as well as replication of the viral genome. Various host factors and processes have been implicated in regulation of the IAV polymerase function, including post-translational modifications, however the mechanisms are not fully understood...
September 28, 2016: Journal of Virology
https://www.readbyqxmd.com/read/27613581/heterogeneous-structures-formed-by-conserved-rna-sequences-within-the-hiv-reverse-transcription-initiation-site
#17
Aaron Coey, Kevin Larsen, Joseph D Puglisi, Elisabetta Viani Puglisi
Reverse transcription is a key process in the early steps of HIV infection. This process initiates within a specific complex formed by the 5' UTR of the HIV genomic RNA (vRNA) and a host primer tRNA(Lys)3 Using nuclear magnetic resonance (NMR) spectroscopy and single-molecule fluorescence spectroscopy, we detect two distinct conformers adopted by the tRNA/vRNA initiation complex. We directly show that an interaction between the conserved 8-nucleotide viral RNA primer activation signal (PAS) and the primer tRNA occurs in one of these conformers...
November 2016: RNA
https://www.readbyqxmd.com/read/27601575/complete-and-incomplete-genome-packaging-of-influenza-a-and-b-viruses
#18
Sumiho Nakatsu, Hiroshi Sagara, Yuko Sakai-Tagawa, Norio Sugaya, Takeshi Noda, Yoshihiro Kawaoka
UNLABELLED: The genomes of influenza A and B viruses comprise eight segmented, single-stranded, negative-sense viral RNAs (vRNAs). Although segmentation of the virus genome complicates the packaging of infectious progeny into virions, it provides an evolutionary benefit in that it allows viruses to exchange vRNAs with other strains. Influenza A viruses are believed to package their eight different vRNAs in a specific manner. However, several studies have shown that many viruses are noninfectious and fail to package at least one vRNA...
2016: MBio
https://www.readbyqxmd.com/read/27556479/influenza-na-and-pb1-gene-segments-interact-during-the-formation-of-viral-progeny-localization-of-the-binding-region-within-the-pb1-gene
#19
Brad Gilbertson, Tian Zheng, Marie Gerber, Anne Printz-Schweigert, Chi Ong, Roland Marquet, Catherine Isel, Steven Rockman, Lorena Brown
The influenza A virus genome comprises eight negative-sense viral RNAs (vRNAs) that form individual ribonucleoprotein (RNP) complexes. In order to incorporate a complete set of each of these vRNAs, the virus uses a selective packaging mechanism that facilitates co-packaging of specific gene segments but whose molecular basis is still not fully understood. Recently, we used a competitive transfection model where plasmids encoding the A/Puerto Rico/8/34 (PR8) and A/Udorn/307/72 (Udorn) PB1 gene segments were competed to show that the Udorn PB1 gene segment is preferentially co-packaged into progeny virions with the Udorn NA gene segment...
2016: Viruses
https://www.readbyqxmd.com/read/27517951/experimental-approaches-to-study-genome-packaging-of-influenza-a-viruses
#20
REVIEW
Catherine Isel, Sandie Munier, Nadia Naffakh
The genome of influenza A viruses (IAV) consists of eight single-stranded negative sense viral RNAs (vRNAs) encapsidated into viral ribonucleoproteins (vRNPs). It is now well established that genome packaging (i.e., the incorporation of a set of eight distinct vRNPs into budding viral particles), follows a specific pathway guided by segment-specific cis-acting packaging signals on each vRNA. However, the precise nature and function of the packaging signals, and the mechanisms underlying the assembly of vRNPs into sub-bundles in the cytoplasm and their selective packaging at the viral budding site, remain largely unknown...
2016: Viruses
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