Impact of Influenza A Virus Infection on the Proteomes of Human Bronchoepithelial Cells from Different Donors

Susceptibility to influenza A virus
is determined by a balance
of viral and host factors. The genetic background of the host contributes
to the severity of disease, but the influenza-related proteomes of
cells from different individuals have not been compared. We used high-resolution
mass spectrometry to identify proteins in normal human bronchial epithelial
(NHBE) cells isolated from three different donors. Infection of each
NHBE cell culture with influenza A/California/07/2009 (H1N1) resulted
in expression of viral proteins and a variety of host proteins, including
interferons, interferon-stimulated genes, and secreted chemokines/cytokines.
The expression level of viral proteins corresponded to the level of
host proteins that support influenza infection (i.e., pro-viral proteins);
however, production of infectious virus was inversely related to the
levels of antiviral proteins, suggesting that a balance of pro-viral
proteins and the antiviral response controls virus replication. In
summary, our results demonstrate that expression levels of pro-viral
as well as antiviral factors are different for each donor and suggest
that relative quantitation of these factors may provide a way to identify
individuals or population groups who are susceptible to severe influenza
disease.