RT Journal Article
SR Electronic
T1 An alternative AUG codon that produces an N-terminally extended form of the influenza A virus NP is a virulence factor for a swine-derived virus
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 738427
DO 10.1101/738427
A1 Helen M. Wise
A1 Eleanor Gaunt
A1 Jihui Ping
A1 Barbara Holzer
A1 Seema Jasim
A1 Samantha J. Lycett
A1 Lita Murphy
A1 Alana Livesey
A1 Russell Brown
A1 Nikki Smith
A1 Sophie Morgan
A1 Becky Clark
A1 Katerine Kudryavtseva
A1 Philippa M. Beard
A1 Jonathan Nguyen-Van-Tam
A1 Francisco J. Salguero
A1 Elma Tchilian
A1 Bernadette M. Dutia
A1 Earl G. Brown
A1 Paul Digard
YR 2019
UL http://biorxiv.org/content/early/2019/08/19/738427.abstract
AB The 2009 influenza A virus (IAV) pandemic (pdm2009) was caused by a swine H1N1 virus with several atypical genetic features. Here, we investigate the origin and significance of an upstream AUG (uAUG) codon in the 5’-untranslated region of the NP gene. Phylogeny indicated that the uAUG codon arose in the classical swine IAV lineage in the mid 20th Century, and has become fixed in the current triple reassortant, variant pdm2009 swine IAV and human pdm2009 lineages. Functionally, it supports leaky ribosomal initiation in vitro and in vivo to produce two isoforms of NP: canonical, and a longer “eNP”. The uAUG codon had little effect on viral gene expression or replication in vitro. However, in both murine and porcine models of IAV infection, removing the uAUG codon gene attenuated pdm2009 virus pathogenicity. Thus, the NP uAUG codon is a virulence factor for swine IAVs with proven zoonotic ability.