Influenza A Virus Expresses High Levels of an Unusual Class of Small Viral Leader RNAs in Infected Cells

ABSTRACT Evidence 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 v...

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Autores principales:	Jennifer L. Umbach, Hui-Ling Yen, Leo L. M. Poon, Bryan R. Cullen
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2010
Materias:	Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/2c618a9b0c5c44d8a513829422c08dd2
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spelling	oai:doaj.org-article:2c618a9b0c5c44d8a513829422c08dd22021-11-15T15:38:15ZInfluenza A Virus Expresses High Levels of an Unusual Class of Small Viral Leader RNAs in Infected Cells10.1128/mBio.00204-102150-7511https://doaj.org/article/2c618a9b0c5c44d8a513829422c08dd22010-10-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.00204-10https://doaj.org/toc/2150-7511ABSTRACT Evidence 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.Jennifer L. UmbachHui-Ling YenLeo L. M. PoonBryan R. CullenAmerican Society for MicrobiologyarticleMicrobiologyQR1-502ENmBio, Vol 1, Iss 4 (2010)
institution	DOAJ
collection	DOAJ
language	EN
topic	Microbiology QR1-502
spellingShingle	Microbiology QR1-502 Jennifer L. Umbach Hui-Ling Yen Leo L. M. Poon Bryan R. Cullen Influenza A Virus Expresses High Levels of an Unusual Class of Small Viral Leader RNAs in Infected Cells
description	ABSTRACT Evidence 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.
format	article
author	Jennifer L. Umbach Hui-Ling Yen Leo L. M. Poon Bryan R. Cullen
author_facet	Jennifer L. Umbach Hui-Ling Yen Leo L. M. Poon Bryan R. Cullen
author_sort	Jennifer L. Umbach
title	Influenza A Virus Expresses High Levels of an Unusual Class of Small Viral Leader RNAs in Infected Cells
title_short	Influenza A Virus Expresses High Levels of an Unusual Class of Small Viral Leader RNAs in Infected Cells
title_full	Influenza A Virus Expresses High Levels of an Unusual Class of Small Viral Leader RNAs in Infected Cells
title_fullStr	Influenza A Virus Expresses High Levels of an Unusual Class of Small Viral Leader RNAs in Infected Cells
title_full_unstemmed	Influenza A Virus Expresses High Levels of an Unusual Class of Small Viral Leader RNAs in Infected Cells
title_sort	influenza a virus expresses high levels of an unusual class of small viral leader rnas in infected cells
publisher	American Society for Microbiology
publishDate	2010
url	https://doaj.org/article/2c618a9b0c5c44d8a513829422c08dd2
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Influenza A Virus Expresses High Levels of an Unusual Class of Small Viral Leader RNAs in Infected Cells

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