Journal Article
Journal of Virology, vol. 80, iss. 21, pp. 10813-10828, 2006
Authors
T. Baas, C. R. Baskin, D. L. Diamond, A. García-Sastre, H. Bielefeldt-Ohmann, T. M. Tumpey, M. J. Thomas, V. S. Carter, T. H. Teal, N. Van Hoeven, S. Proll, J. M. Jacobs, Z. R. Caldwell, M. A. Gritsenko, R. R. Hukkanen, D. G. Camp, R. D. Smith, M. G. Katze
Abstract
ABSTRACT
Recent
outbreaks of avian influenza in humans have stressed the need for an
improved nonhuman primate model of influenza pathogenesis. In order to
further develop a macaque model, we expanded our previous in vivo
genomics experiments with influenza virus-infected macaques by focusing
on the innate immune response at day 2 postinoculation and on gene
expression in affected lung tissue with viral genetic material present.
Finally, we sought to identify signature genes for early infection in
whole blood. For these purposes, we infected six pigtailed macaques
(
Macaca nemestrina
) with reconstructed influenza A/Texas/36/91
virus and three control animals with a sham inoculate. We sacrificed
one control and two experimental animals at days 2, 4, and 7
postinfection. Lung tissue was harvested for pathology, gene expression
profiling, and proteomics. Blood was collected for genomics every other
day from each animal until the experimental endpoint. Gross and
microscopic pathology, immunohistochemistry, viral gene expression by
arrays, and/or quantitative real-time reverse
transcription-PCR confirmed successful yet mild infections
in all experimental animals. Genomic experiments were performed using
macaque-specific oligonucleotide arrays, and high-throughput proteomics
revealed the host response to infection at the mRNA and protein levels.
Our data showed dramatic differences in gene expression within regions
in influenza virus-induced lesions based on the presence or absence of
viral mRNA. We also identified genes tightly coregulated in peripheral
white blood cells and in lung tissue at day 2 postinoculation. This
latter finding opens the possibility of using gene expression arrays on
whole blood to detect infection after exposure but prior to onset of
symptoms or
shedding.