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Article: Influenza a virus expresses high levels of an unusual class of small viral leader RNAs in infected cells

TitleInfluenza a virus expresses high levels of an unusual class of small viral leader RNAs in infected cells
Authors
KeywordsBiology
Microbiology
Issue Date2010
PublisherAmerican Society for Microbiology. The Journal's web site is located at http://mbio.asm.org
Citation
Mbio, 2010, v. 1 n. 4 How to Cite?
AbstractEvidence has recently accumulated suggesting that small noncoding RNAs, and particularly microRNAs, have the potential to strongly affect the replication and pathogenic potential of a range of human virus species. Here, we report the use of deep sequencing to comprehensively analyze small viral RNAs (18 to 27 nucleotides [nt]) produced during infection by influenza A virus. Although influenza A virus differs from most other RNA viruses in that it replicates its genome in the nucleus and is therefore exposed to the nuclear microRNA processing factors Drosha and DGCR8, we did not observe any microRNAs encoded by influenza virus genes. However, influenza virus infection did induce the expression of very high levels- over 100,000 copies per cell by 8 h postinfection- of a population of 18- to 27-nt small viral leader RNAs (leRNAs) that originated from the precise 5′ ends of all eight influenza virus genomic RNA (vRNA) segments. Like the vRNAs themselves, our data indicate that the leRNAs also bear a 5′-terminal triphosphate and are therefore not capable of functioning as microRNAs. Instead, the high-level production of leRNAs may imply a role in another aspect of the viral life cycle, such as regulation of the switch from viral mRNA transcription to genomic RNA synthesis. IMPORTANCE: Influenza A virus is an important human pathogen that has the potential to give rise to serious pandemics. Here, we demonstrate that influenza A virus induces the expression of very high levels of small viral leader RNAs (leRNAs) within hours of infection. These RNAs are unusual in that they bear a 5' triphosphate and originate from the very 5' ends of the eight viral genomic RNA (vRNA) segments. Their high expression may imply an important role in the viral life cycle that could potentially serve as a novel target for antiviral drugs. © 2010 Umbach et al.
Persistent Identifierhttp://hdl.handle.net/10722/128526
ISSN
2015 Impact Factor: 6.975
2015 SCImago Journal Rankings: 3.543
PubMed Central ID
ISI Accession Number ID
Funding AgencyGrant Number
National Institutes of HealthR21-AI088327
T32-CA009111
NIAIDHHSN26620070005C
American Lebanese Syrian Associated Charities (ALSAC)
University Grants CommitteeAoE/M-12/06
Funding Information:

This research was supported by National Institutes of Health grant R21-AI088327 to B.R.C. H.-L.Y. was supported in part by NIAID contract HHSN26620070005C, the American Lebanese Syrian Associated Charities (ALSAC), and the Area of Excellence Scheme of the University Grants Committee (grant AoE/M-12/06). J.L.U. was supported by NIH training grant T32-CA009111.

References
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DC FieldValueLanguage
dc.contributor.authorUmbach, JLen_HK
dc.contributor.authorYen, HLen_HK
dc.contributor.authorPoon, LLMen_HK
dc.contributor.authorCullen, BRen_HK
dc.date.accessioned2010-11-01T08:57:15Z-
dc.date.available2010-11-01T08:57:15Z-
dc.date.issued2010en_HK
dc.identifier.citationMbio, 2010, v. 1 n. 4en_HK
dc.identifier.issn2150-7511en_HK
dc.identifier.urihttp://hdl.handle.net/10722/128526-
dc.description.abstractEvidence has recently accumulated suggesting that small noncoding RNAs, and particularly microRNAs, have the potential to strongly affect the replication and pathogenic potential of a range of human virus species. Here, we report the use of deep sequencing to comprehensively analyze small viral RNAs (18 to 27 nucleotides [nt]) produced during infection by influenza A virus. Although influenza A virus differs from most other RNA viruses in that it replicates its genome in the nucleus and is therefore exposed to the nuclear microRNA processing factors Drosha and DGCR8, we did not observe any microRNAs encoded by influenza virus genes. However, influenza virus infection did induce the expression of very high levels- over 100,000 copies per cell by 8 h postinfection- of a population of 18- to 27-nt small viral leader RNAs (leRNAs) that originated from the precise 5′ ends of all eight influenza virus genomic RNA (vRNA) segments. Like the vRNAs themselves, our data indicate that the leRNAs also bear a 5′-terminal triphosphate and are therefore not capable of functioning as microRNAs. Instead, the high-level production of leRNAs may imply a role in another aspect of the viral life cycle, such as regulation of the switch from viral mRNA transcription to genomic RNA synthesis. IMPORTANCE: Influenza A virus is an important human pathogen that has the potential to give rise to serious pandemics. Here, we demonstrate that influenza A virus induces the expression of very high levels of small viral leader RNAs (leRNAs) within hours of infection. These RNAs are unusual in that they bear a 5' triphosphate and originate from the very 5' ends of the eight viral genomic RNA (vRNA) segments. Their high expression may imply an important role in the viral life cycle that could potentially serve as a novel target for antiviral drugs. © 2010 Umbach et al.en_HK
dc.languageeng-
dc.publisherAmerican Society for Microbiology. The Journal's web site is located at http://mbio.asm.orgen_HK
dc.relation.ispartofmBioen_HK
dc.rightsMBio. Copyright © American Society for Microbiology.-
dc.rightsCopyright © American Society for Microbiology, [insert journal name, volume number, page numbers, and year]-
dc.subjectBiology-
dc.subjectMicrobiology-
dc.titleInfluenza a virus expresses high levels of an unusual class of small viral leader RNAs in infected cellsen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=2150-7511&volume=1&issue=4 article no. e00204-10&spage=&epage=&date=2010&atitle=Influenza+A+virus+expresses+high+levels+of+an+unusual+class+of+small+viral+leader+RNAs+in+infected+cells-
dc.identifier.emailYen, HL: hyen@hku.hken_HK
dc.identifier.emailPoon, LLM: llmpoon@hkucc.hku.hken_HK
dc.identifier.authorityYen, HL=rp00304en_HK
dc.identifier.authorityPoon, LLM=rp00484en_HK
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1128/mBio.00204-10en_HK
dc.identifier.pmid20842206-
dc.identifier.pmcidPMC2934610-
dc.identifier.scopuseid_2-s2.0-79952068189en_HK
dc.identifier.hkuros183197-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-79952068189&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume1en_HK
dc.identifier.issue4en_HK
dc.identifier.isiWOS:000284718000005-
dc.publisher.placeUnited Statesen_HK
dc.relation.projectControl of Pandemic and Inter-pandemic Influenza-
dc.identifier.scopusauthoridUmbach, JL=24468950800en_HK
dc.identifier.scopusauthoridYen, HL=7102476668en_HK
dc.identifier.scopusauthoridPoon, LLM=7005441747en_HK
dc.identifier.scopusauthoridCullen, BR=7201606883en_HK

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