Avian Influenza Virus PB1 Gene in H3N2 Viruses Evolved in Humans To Reduce Interferon Inhibition by Skewing Codon Usage toward Interferon-Altered tRNA Pools

ABSTRACT Influenza A viruses cause an annual contagious respiratory disease in humans and are responsible for periodic high-mortality human pandemics. Pandemic influenza A viruses usually result from the reassortment of gene segments between human and avian influenza viruses. These avian influenza v...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Bartram L. Smith, Guifang Chen, Claus O. Wilke, Robert M. Krug
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2018
Materias:	codon usage evolution influenza A virus influenza PB1 protein interferon Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/16c486b3f1e04a7c9c1141fb0fa257e0
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:16c486b3f1e04a7c9c1141fb0fa257e0
record_format	dspace
spelling	oai:doaj.org-article:16c486b3f1e04a7c9c1141fb0fa257e02021-11-15T16:00:15ZAvian Influenza Virus PB1 Gene in H3N2 Viruses Evolved in Humans To Reduce Interferon Inhibition by Skewing Codon Usage toward Interferon-Altered tRNA Pools10.1128/mBio.01222-182150-7511https://doaj.org/article/16c486b3f1e04a7c9c1141fb0fa257e02018-09-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.01222-18https://doaj.org/toc/2150-7511ABSTRACT Influenza A viruses cause an annual contagious respiratory disease in humans and are responsible for periodic high-mortality human pandemics. Pandemic influenza A viruses usually result from the reassortment of gene segments between human and avian influenza viruses. These avian influenza virus gene segments need to adapt to humans. Here we focus on the human adaptation of the synonymous codons of the avian influenza virus PB1 gene of the 1968 H3N2 pandemic virus. We generated recombinant H3N2 viruses differing only in codon usage of PB1 mRNA and demonstrated that codon usage of the PB1 mRNA of recent H3N2 virus isolates enhances replication in interferon (IFN)-treated human cells without affecting replication in untreated cells, thereby partially alleviating the interferon-induced antiviral state. High-throughput sequencing of tRNA pools explains the reduced inhibition of replication by interferon: the levels of some tRNAs differ between interferon-treated and untreated human cells, and evolution of the codon usage of H3N2 PB1 mRNA is skewed toward interferon-altered human tRNA pools. Consequently, the avian influenza virus-derived PB1 mRNAs of modern H3N2 viruses have acquired codon usages that better reflect tRNA availabilities in IFN-treated cells. Our results indicate that the change in tRNA availabilities resulting from interferon treatment is a previously unknown aspect of the antiviral action of interferon, which has been partially overcome by human-adapted H3N2 viruses. IMPORTANCE Pandemic influenza A viruses that cause high human mortality usually result from reassortment of gene segments between human and avian influenza viruses. These avian influenza virus gene segments need to adapt to humans. Here we focus on the human adaptation of the avian influenza virus PB1 gene that was incorporated into the 1968 H3N2 pandemic virus. We demonstrate that the coding sequence of the PB1 mRNA of modern H3N2 viruses enhances replication in human cells in which interferon has activated a potent antiviral state. Reduced interferon inhibition results from evolution of PB1 mRNA codons skewed toward the pools of tRNAs in interferon-treated human cells, which, as shown here, differ significantly from the tRNA pools in untreated human cells. Consequently, avian influenza virus-derived PB1 mRNAs of modern H3N2 viruses have acquired codon usages that better reflect tRNA availabilities in IFN-treated cells and are translated more efficiently.Bartram L. SmithGuifang ChenClaus O. WilkeRobert M. KrugAmerican Society for Microbiologyarticlecodon usageevolutioninfluenza A virusinfluenza PB1 proteininterferonMicrobiologyQR1-502ENmBio, Vol 9, Iss 4 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	codon usage evolution influenza A virus influenza PB1 protein interferon Microbiology QR1-502
spellingShingle	codon usage evolution influenza A virus influenza PB1 protein interferon Microbiology QR1-502 Bartram L. Smith Guifang Chen Claus O. Wilke Robert M. Krug Avian Influenza Virus PB1 Gene in H3N2 Viruses Evolved in Humans To Reduce Interferon Inhibition by Skewing Codon Usage toward Interferon-Altered tRNA Pools
description	ABSTRACT Influenza A viruses cause an annual contagious respiratory disease in humans and are responsible for periodic high-mortality human pandemics. Pandemic influenza A viruses usually result from the reassortment of gene segments between human and avian influenza viruses. These avian influenza virus gene segments need to adapt to humans. Here we focus on the human adaptation of the synonymous codons of the avian influenza virus PB1 gene of the 1968 H3N2 pandemic virus. We generated recombinant H3N2 viruses differing only in codon usage of PB1 mRNA and demonstrated that codon usage of the PB1 mRNA of recent H3N2 virus isolates enhances replication in interferon (IFN)-treated human cells without affecting replication in untreated cells, thereby partially alleviating the interferon-induced antiviral state. High-throughput sequencing of tRNA pools explains the reduced inhibition of replication by interferon: the levels of some tRNAs differ between interferon-treated and untreated human cells, and evolution of the codon usage of H3N2 PB1 mRNA is skewed toward interferon-altered human tRNA pools. Consequently, the avian influenza virus-derived PB1 mRNAs of modern H3N2 viruses have acquired codon usages that better reflect tRNA availabilities in IFN-treated cells. Our results indicate that the change in tRNA availabilities resulting from interferon treatment is a previously unknown aspect of the antiviral action of interferon, which has been partially overcome by human-adapted H3N2 viruses. IMPORTANCE Pandemic influenza A viruses that cause high human mortality usually result from reassortment of gene segments between human and avian influenza viruses. These avian influenza virus gene segments need to adapt to humans. Here we focus on the human adaptation of the avian influenza virus PB1 gene that was incorporated into the 1968 H3N2 pandemic virus. We demonstrate that the coding sequence of the PB1 mRNA of modern H3N2 viruses enhances replication in human cells in which interferon has activated a potent antiviral state. Reduced interferon inhibition results from evolution of PB1 mRNA codons skewed toward the pools of tRNAs in interferon-treated human cells, which, as shown here, differ significantly from the tRNA pools in untreated human cells. Consequently, avian influenza virus-derived PB1 mRNAs of modern H3N2 viruses have acquired codon usages that better reflect tRNA availabilities in IFN-treated cells and are translated more efficiently.
format	article
author	Bartram L. Smith Guifang Chen Claus O. Wilke Robert M. Krug
author_facet	Bartram L. Smith Guifang Chen Claus O. Wilke Robert M. Krug
author_sort	Bartram L. Smith
title	Avian Influenza Virus PB1 Gene in H3N2 Viruses Evolved in Humans To Reduce Interferon Inhibition by Skewing Codon Usage toward Interferon-Altered tRNA Pools
title_short	Avian Influenza Virus PB1 Gene in H3N2 Viruses Evolved in Humans To Reduce Interferon Inhibition by Skewing Codon Usage toward Interferon-Altered tRNA Pools
title_full	Avian Influenza Virus PB1 Gene in H3N2 Viruses Evolved in Humans To Reduce Interferon Inhibition by Skewing Codon Usage toward Interferon-Altered tRNA Pools
title_fullStr	Avian Influenza Virus PB1 Gene in H3N2 Viruses Evolved in Humans To Reduce Interferon Inhibition by Skewing Codon Usage toward Interferon-Altered tRNA Pools
title_full_unstemmed	Avian Influenza Virus PB1 Gene in H3N2 Viruses Evolved in Humans To Reduce Interferon Inhibition by Skewing Codon Usage toward Interferon-Altered tRNA Pools
title_sort	avian influenza virus pb1 gene in h3n2 viruses evolved in humans to reduce interferon inhibition by skewing codon usage toward interferon-altered trna pools
publisher	American Society for Microbiology
publishDate	2018
url	https://doaj.org/article/16c486b3f1e04a7c9c1141fb0fa257e0
work_keys_str_mv	AT bartramlsmith avianinfluenzaviruspb1geneinh3n2virusesevolvedinhumanstoreduceinterferoninhibitionbyskewingcodonusagetowardinterferonalteredtrnapools AT guifangchen avianinfluenzaviruspb1geneinh3n2virusesevolvedinhumanstoreduceinterferoninhibitionbyskewingcodonusagetowardinterferonalteredtrnapools AT clausowilke avianinfluenzaviruspb1geneinh3n2virusesevolvedinhumanstoreduceinterferoninhibitionbyskewingcodonusagetowardinterferonalteredtrnapools AT robertmkrug avianinfluenzaviruspb1geneinh3n2virusesevolvedinhumanstoreduceinterferoninhibitionbyskewingcodonusagetowardinterferonalteredtrnapools
_version_	1718426949905285120

Avian Influenza Virus PB1 Gene in H3N2 Viruses Evolved in Humans To Reduce Interferon Inhibition by Skewing Codon Usage toward Interferon-Altered tRNA Pools

Ejemplares similares