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Restoring PB1-F2 into the 2009 Pandemic H1N1 Influenza Virus has minimal effects in swine

tetano

Editor, Senior Moderator
J Virol. 2012 Feb 29. [Epub ahead of print]
Restoring PB1-F2 into the 2009 Pandemic H1N1 Influenza Virus has minimal effects in swine.
Pena L, Vincent AL, Loving CL, Henningson JN, Lager KM, Lorusso A, Perez DR.
Source

Department of Veterinary Medicine, University of Maryland, College Park and Virginia-Maryland Regional College of Veterinary Medicine, College Park, Maryland, USA.
Abstract

PB1-F2 is an 87-90 amino acid long protein expressed by certain influenza A viruses. Previous studies have shown that PB1-F2 contributes to virulence in the mouse model; however, its role in natural hosts - pigs, humans, or birds - remains largely unknown. Outbreaks of domestic pigs infected with the 2009 pandemic H1N1 influenza virus (pH1N1) have been detected worldwide. Unlike previous pandemic strains, pH1N1 viruses do not encode a functional PB1-F2 due to the presence of three stop codons resulting in premature truncation after codon 11. However, pH1N1s have the potential to acquire the full-length form of PB1-F2 through mutation or reassortment. In this study, we assessed whether restoring the full-length PB1-F2 ORF in the pH1N1 background would have an effect in virus replication and virulence in pigs. Restoring the PB1-F2 ORF resulted in up-regulation of viral polymerase activity at early time points in vitro and enhanced virus yields in porcine respiratory explants and in the lungs of infected pigs. There was an increase in the severity of pneumonia in pigs infected with isogenic virus expressing PB1-F2 as compared to the WT pH1N1. The extent of microscopic pneumonia correlated with increased pulmonary levels of IFN-α and IL-1β in pigs infected with pH1N1 encoding a functional PB1-F2 but only early in the infection. Together, our results indicate that PB1-F2 in the context of pH1N1 moderately modulates viral replication, lung histopathology, and local cytokine response in pigs.

PMID:
22379102
[PubMed - as supplied by publisher]

http://www.ncbi.nlm.nih.gov/pubmed/22379102
 
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