The molecular basis of adenovirus pathogenesis.
The pathology of type 5 (Ad5) pneumonia in Sigmodon hispidus cotton rats is closely similar to that in humans. Virus replicates in bronchiolar epithelial cells, but in situ hybridization shows early gene expression in macrophage/monocytes in alveoli and hilar lymph nodes. Only early gene expression is required to produce the pathology of which there is an "early" and a "late" phase. The early region 3 (E3), which does not function in viral replication, plays an important role in the natural history of at least the subgroup C adenoviruses (types 1, 2, 5, 6), which produce latent infections in host-infected lymphocytes: The 19-kDa glycoprotein markedly reduces the transport of the class I MHC to the surface of infected cells and, therefore, the attack of cytotoxic T cells, which could eliminate infected cells. When this gene is mutated, the late-phase inflammatory response to infection is markedly increased. The E3 14.7-kDa protein reduces the presence of polymorphonuclear leukocytes in the early-phase pathological inflammatory exudate. The E1B 55-kDa is essential to effect the late phase, and when its gene is mutated, the inflammation is greatly reduced although viral replication is not affected. Because only early genes are required to induce the complete pathogenesis of adenovirus infection in cotton rats, it is possible to produce the same pneumonia in lungs of mice in which only adenovirus early genes are expressed.(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Microbiology, College of Physicians and Surgeons, Columbia University, New York.
H S
HS
Ginsberg
G A
GA
Prince
D000257:Adenoviridae Infections / Q000276:immunology / Q000821:virology*; D000258:Adenovirus Infections, Human / Q000276:immunology / Q000821:virology*; D000260:Adenoviruses, Human / Q000235:genetics / Q000302:isolation & purification / Q000472:pathogenicity*; D000818:Animals; D002478:Cells, Cultured; D004195:Disease Models, Animal; D015870:Gene Expression; D005814:Genes, Viral / Q000235:genetics*; D006801:Humans; D051379:Mice; D008815:Mice, Inbred Strains; D011024:Pneumonia, Viral / Q000276:immunology / Q000821:virology*; D051381:Rats; D016205:Sigmodontinae