Closely Related Influenza Viruses Induce Contrasting Respiratory Tract Immunopathology

• Type of Material: Article
• Authors: Vy L. Le, Emory University; Cynthia L. Courtney, Emory University; John Steel, Emory University; Richard W Compans, Emory University
• Language: English
• Date: 2013
• Publisher: Public Library of Science
• Publication Version: Final Published Version
• Copyright Statement: © 2013 Le et al.
• License: Creative Commons Attribution 3.0 Unported
• Final Published Version (URL): http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0076708
• Title of Journal or Parent Work: PLoS ONE
• ISSN: 1932-6203
• Volume: 8
• Issue: 9
• Start Page: e76708
• End Page: e76708
• Grant/Funding Information: V.L. Le is supported by NIH grant T32-A1074492 and J. Steel is supported through a pilot project from the Centers for Excellence in Influenza Research and Surveillance (CEIRS) contract number HHSN266200700006C.; This study was supported by National Institutes of Health (NIH) grants A1074579, P51OD11132 and a Queensland Institute of Medical Research-Australian Center for Vaccine Development and Emory Vaccine Center (ACVD-EVC) Pilot projects.
• Research Categories: Health Sciences, General; Health Sciences, Immunology

Abstract

The swine-origin H1N1 virus which emerged in 2009 resulted in the first influenza pandemic of the 21st century. Although the majority of infections were moderate, a significant proportion of infections were severe and characterized by acute respiratory distress syndrome and pulmonary edema. We compared two isolates from the 2009 H1N1 pandemic; A/California/07/09 (CA/07) and A/Netherlands/602/09 (NL/602) viruses that share greater than 99% sequence identity. Though genetically similar, these viruses exhibit contrasting pathological effects. Mice that were infected with 800 plaque forming unit (PFU) of CA/07 virus rapidly lost weight, which was concurrent with detection of high pulmonary concentrations of MCP-1, MIG, IP-10 and TIMP-1. Initially, severe bronchiolar epithelial necrosis and acute respiratory distress was observed, followed by marked bronchiolar epithelial hyperplasia. Mononuclear cell infiltration was initially localized to perivascular and peribronchiolar interstitium and then spread to adjacent alveoli. Infiltrating cells were phenotypically CD11bhi, F4/80lo. In contrast, when mice were infected with 800 PFU of NL/602 virus, minimal weight loss was observed, and concentrations of cytokines in the lung were significantly lower. Inflammation was primarily restricted to the bronchioles and perivascular interstitium with minimal spread to alveoli. Infiltrating cells include foamy macrophages and surface markers were characterized as CD11blo/-, F4/80hi. These two genetically similar viruses can be useful strains with which to investigate immune-regulatory determinants of pathogenesis of influenza virus.