Role of early region 3 (E3) in pathogenesis of adenovirus disease.
The cotton rat Sigmodon hispidus has provided an animal model of adenovirus pneumonia that permits investigation of the viral gene products required to produce the disease and the molecular mechanisms effecting the damage. This study was carried out to test the hypothesis that early region 3 (E3) of the adenovirus genome plays a critical role in pathogenesis of the virus's disease process even though none of its gene products are essential for its replication. Mutants whose E3 region is largely deleted (i.e., H2dl801 and H5dl327) replicated like wild-type virus in the cotton rats' lungs, but the lymphocyte and macrophage/monocyte inflammatory response was markedly increased. Viruses containing mutations that ablated production of the 19-kDa glycoprotein had the same effect as H2dl801 and H5dl327. However, mutants with deletions in the other E3 open reading frames, some of which encode known proteins, did not differ from wild-type virus in their pathogenic properties. The 19-kDa glycoprotein markedly reduces expression of the class I major histocompatibility complex antigens on the surface of infected cells. A complete correlation was found between those mutants that had increased pathogenic effects and those that lost the ability to reduce transport of the class I major histocompatibility complex antigens to surface of infected cells (i.e., all mutants unable to express the 19-kDa glycoprotein). H5sub304, which has a deletion between 83.2 and 85.1 map units in the E3B region and expresses the 19-kDa glycoprotein, did not increase the extent of pneumonia but qualitatively changed the inflammatory response in that increased numbers of polymorphonuclear leukocytes accumulated, often in small foci.
Ginsberg
H S
HS
Department of Medicine, Columbia University College of Physicians and Surgeons, New York, NY 10032.
Lundholm-Beauchamp
U
U
Horswood
R L
RL
Pernis
B
B
Wold
W S
WS
Chanock
R M
RM
Prince
G A
GA
D000260:Adenoviruses, Human / Q000235:genetics / Q000472:pathogenicity*; D000818:Animals; D002872:Chromosome Deletion; D004252:DNA Mutational Analysis; D005814:Genes, Viral; D006023:Glycoproteins / Q000235:genetics; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D008168:Lung / Q000473:pathology; D009115:Muridae; D011024:Pneumonia, Viral / Q000382:microbiology* / Q000473:pathology; D014764:Viral Proteins / Q000235:genetics
D006023:Glycoproteins; D015395:Histocompatibility Antigens Class I; D014764:Viral Proteins