Extrapulmonary tissue responses in cynomolgus macaques (Macaca fascicularis) infected with highly pathogenic avian influenza A (H5N1) virus.
The mechanisms responsible for virulence of influenza viruses in humans remain poorly understood. A prevailing hypothesis is that the highly pathogenic virus isolates cause a severe cytokinemia precipitating acute respiratory distress syndrome and multiple organ dysfunction syndrome. Cynomolgus macaques (Macaca fascicularis) infected with a human highly pathogenic avian influenza (HPAI) H5N1 virus isolate (A/Vietnam/1203/2004) or reassortants of human influenza virus A/Texas/36/91 (H1N1) containing genes from the 1918 pandemic influenza A (H1N1) virus developed severe pneumonia within 24 h postinfection. However, virus spread beyond the lungs was only detected in the H5N1 group, and signs of extrapulmonary tissue reactions, including microglia activation and sustained up-regulation of inflammatory markers, most notably hypoxia inducible factor-1alpha (HIF-1alpha), were largely limited to this group. Extrapulmonary pathology may thus contribute to the morbidities induced by H5N1 viruses.
Tolnay
A-E
AE
Department of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins, CO, USA.
Baskin
C R
CR
Tumpey
T M
TM
Sabourin
P J
PJ
Sabourin
C L
CL
Long
J P
JP
Pyles
J A
JA
Albrecht
R A
RA
García-Sastre
A
A
Katze
M G
MG
Bielefeldt-Ohmann
H
H
D000818:Animals; D016207:Cytokines / Q000378:metabolism; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism*; D053124:Influenza A Virus, H5N1 Subtype / Q000472:pathogenicity*; D008099:Liver / Q000473:pathology*; D008252:Macaca fascicularis; D017628:Microglia / Q000276:immunology*; D009976:Orthomyxoviridae Infections / Q000276:immunology / Q000473:pathology / Q000503:physiopathology*; D012137:Respiratory System / Q000473:pathology; D015854:Up-Regulation; D014774:Virulence
D016207:Cytokines; D051795:Hypoxia-Inducible Factor 1, alpha Subunit