Adenovirus-induced liver pathology is mediated through TNF receptors I and II but is independent of TNF or lymphotoxin.
Mice infected with an adenovirus mutant in which the E3 region is deleted, including TNF-resistance genes, develop fatal liver pathology within 3-4 days after infection. At least 10-fold more wild-type virus was needed to cause comparable pathology. These results indicate that the E3 region is critically involved in modulating the pathogenesis of adenovirus infection and that TNF may play a role in liver damage. To explore the latter possibility, the course of disease was examined in infected mice lacking TNFR-I and/or TNFRII, TNF only, or both TNF and lymphotoxin-alpha. Only mice lacking both TNFRI and TNFRII were protected from the lethal affects of the mutant adenovirus. Mice deficient in TNF or TNF and lymphotoxin-alpha displayed the fatal pathology. This outcome is consistent with the existence of another related ligand that binds TNFRI/II to mediate liver damage during infection with this mutant.
Division of Immunology, John Curtin School of Medical Research, Australian National University, Canberra.
H
H
Hayder
R V
RV
Blanden
H
H
Körner
D S
DS
Riminton
J D
JD
Sedgwick
A
A
Müllbacher
D000257:Adenoviridae Infections / Q000276:immunology* / Q000473:pathology* / Q000821:virology; D000260:Adenoviruses, Human / Q000235:genetics / Q000276:immunology; D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D004279:DNA, Viral / Q000032:analysis; D005260:Female; D006801:Humans; D007113:Immunity, Innate; D008099:Liver / Q000276:immunology* / Q000473:pathology* / Q000821:virology; D008233:Lymphotoxin-alpha / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D018345:Mice, Knockout; D016133:Polymerase Chain Reaction; D018124:Receptors, Tumor Necrosis Factor / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; D014409:Tumor Necrosis Factor-alpha / Q000172:deficiency / Q000235:genetics / Q000502:physiology*
D015703:Antigens, CD; D004279:DNA, Viral; D008233:Lymphotoxin-alpha; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; D014409:Tumor Necrosis Factor-alpha