title: Deletions in the neuraminidase stalk region of H2N2 and H9N2 avian influenza virus subtypes do not affect postinfluenza secondary bacterial pneumonia.
abstract: We investigated the synergism between influenza virus and Streptococcus pneumoniae, particularly the role of deletions in the stalk region of the neuraminidase (NA) of H2N2 and H9N2 avian influenza viruses. Deletions in the NA stalk (ΔNA) had no effect on NA activity or on the adherence of S. pneumoniae to virus-infected human alveolar epithelial (A549) and mouse lung adenoma (LA-4) cells, although it delayed virus elution from turkey red blood cells. Sequential S. pneumoniae infection of mice previously inoculated with isogenic recombinant H2N2 and H9N2 influenza viruses displayed severe pneumonia, elevated levels of intrapulmonary proinflammatory responses, and death. No differences between the WT and ΔNA mutant viruses were detected with respect to effects on postinfluenza pneumococcal pneumonia as measured by bacterial growth, lung inflammation, morbidity, mortality, and cytokine/chemokine concentrations. Differences were observed, however, in influenza virus-infected mice that were treated with oseltamivir prior to a challenge with S. pneumoniae. Under these circumstances, mice infected with ΔNA viruses were associated with a better prognosis following a secondary bacterial challenge. These data suggest that the H2N2 and H9N2 subtypes of avian influenza A viruses can contribute to secondary bacterial pneumonia and deletions in the NA stalk may modulate its outcome in the context of antiviral therapy.
authors.affiliation: Department of Veterinary Medicine, University of Maryland, College Park, Maryland, USA.
authors.forename: Ashok K
authors.initials: AK
authors.lastname: Chockalingam
authors.forename: Danielle
authors.initials: D
authors.lastname: Hickman
authors.forename: Lindomar
authors.initials: L
authors.lastname: Pena
authors.forename: Jianqiang
authors.initials: J
authors.lastname: Ye
authors.forename: Andrea
authors.initials: A
authors.lastname: Ferrero
authors.forename: Jose R
authors.initials: JR
authors.lastname: Echenique
authors.forename: Hongjun
authors.initials: H
authors.lastname: Chen
authors.forename: Troy
authors.initials: T
authors.lastname: Sutton
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Perez
mesh_terms: D020816:Amino Acid Motifs; D000818:Animals; D001422:Bacterial Adhesion; D002460:Cell Line; D002645:Chickens; D060085:Coinfection / Q000382:microbiology / Q000821:virology; D005260:Female; D017353:Gene Deletion; D006801:Humans; D053121:Influenza A Virus, H2N2 Subtype / Q000737:chemistry / Q000201:enzymology* / Q000235:genetics; D053127:Influenza A Virus, H9N2 Subtype / Q000737:chemistry / Q000201:enzymology* / Q000235:genetics; D005585:Influenza in Birds / Q000821:virology; D007251:Influenza, Human / Q000150:complications / Q000821:virology*; D008168:Lung / Q000382:microbiology / Q000821:virology; D051379:Mice; D008807:Mice, Inbred BALB C; D009439:Neuraminidase / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D018410:Pneumonia, Bacterial / Q000150:complications / Q000382:microbiology*; D013296:Streptococcus pneumoniae / Q000502:physiology*; D014764:Viral Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism
chemical_list: D014764:Viral Proteins; C487630:NA protein, influenza A virus; D009439:Neuraminidase