Canine influenza virus replicates in alveolar macrophages and induces TNF-alpha.
Canine influenza virus (CIV) is a recently emergent pathogen of dogs that has caused highly contagious respiratory disease in racing Greyhounds, pet dogs, and shelter animals. Initial characterizations of CIV-induced respiratory disease suggested alveolar macrophages may be susceptible to virus infection. To investigate the role of the alveolar macrophage in the pathogenesis of CIV infection, primary alveolar macrophages were inoculated with CIV and studied from 0 to 48 hours later. Virus titers in alveolar macrophage culture supernatants increased significantly (P < .05, n = 7) from 3 to 24 hours following virus inoculation. Virus matrix gene expression was significantly increased (P < .05, n = 14) at 3, 6, and 12 hours after inoculation, peaking at 6,445-fold the level of RNA detectable immediately following inoculation. Virus-inoculated macrophages demonstrated significantly (P < .05, n = 5) decreased viability (30% trypan blue positive) by 12 hours after inoculation compared with mock-inoculated cells (5% trypan blue positive). By 12 hours after inoculation, tumor necrosis factor-alpha (TNF-alpha) and interleukin-10 (IL-10) mRNA levels were significantly (P < .05, n = 11) increased over those immediately following inoculation. Only TNF-alpha protein levels were significantly increased (P < .05, n = 11) at 12 hours after inoculation. In conclusion, the results indicate that CIV replicates in canine alveolar macrophages and induces TNF-alpha expression and cell death.
Powe
J R
JR
College of Veterinary Medicine, Department of Infectious Diseases and Pathology, University of Florida, Gainesville, FL, USA. powej@vetmed.ufl.edu
Castleman
W L
WL
D000818:Animals; D016923:Cell Death; D004285:Dogs; D005786:Gene Expression Regulation / Q000502:physiology; D053123:Influenza A Virus, H3N8 Subtype / Q000502:physiology*; D016676:Macrophages, Alveolar / Q000821:virology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism*; D014779:Virus Replication / Q000502:physiology
D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha