Acute inflammatory response and remodeling of airway epithelium after subspecies B1 human adenovirus infection of the mouse lower respiratory tract.
Despite the well-recognized role of adenoviruses of species B in the etiology of severe respiratory disease, the lack of an experimental in vivo model system has limited the understanding of the molecular pathogenesis of species B adenovirus-induced pneumonia. Intratracheal instillation of 5 x 10(8) plaque-forming units (pfu) of adenoviruses 3p and 7h resulted in a robust inflammatory response in the lungs of infected mice. A marked infiltration of neutrophils into the lung air spaces was observed at 1 and 2 days postinfection (dpi), with a concomitant increase in the levels of neutrophil chemokines MIP-2 and KC. The overall histological severity scores were significantly higher for Ad3p-infected mice at 2 dpi, but similar between the two viruses at other time points. Remodeling of the airway epithelia and mucous cell metaplasia were noted in the proximal airways of infected mice, indicating marked epithelial differentiation and/or injury. The proinflammatory cytokines interleukin-beta (IL-1beta), tumor necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma [see symbol in text]), and interleukin-12 (IL-12) were induced by viral infection. Expression of the early viral immunomodulatory genes E3-15.3K and E3gp19K mRNA was readily detectable in the lungs of infected mice by reverse transcription-polymerase chain reaction (RT-PCR) at 1 and 2 dpi, coinciding with the peak levels of TNF-alpha. While the detection of gp19K mRNA declined thereafter, 15.3K mRNA was detectable up to 6 dpi. Our results indicate that human Ad3 and Ad7 cause marked pulmonary pathology, inducing similar host responses in the respiratory tract, thus validating the use of the mouse model for the study of early virus-host interactions during lung infection by adenoviruses of subspecies B1.
Kajon
Adriana E
AE
Lovelace Respiratory Research Institute, Albuquerque, New Mexico, USA.
Gigliotti
Andrew P
AP
Harrod
Kevin S
KS
D000208:Acute Disease; D000258:Adenovirus Infections, Human / Q000473:pathology / Q000821:virology; D000260:Adenoviruses, Human / Q000235:genetics / Q000302:isolation & purification / Q000472:pathogenicity*; D000818:Animals; D016207:Cytokines / Q000096:biosynthesis; D004195:Disease Models, Animal; D004848:Epithelium / Q000473:pathology* / Q000821:virology; D006801:Humans; D007249:Inflammation / Q000276:immunology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011024:Pneumonia, Viral / Q000473:pathology* / Q000821:virology; D012137:Respiratory System / Q000473:pathology* / Q000821:virology; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism
D016207:Cytokines; D014764:Viral Proteins