Adenovirus-induced liver pathology is mediated through TNF receptors I andII 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 da ys after infection, At least 10-fold more wild-type virus was needed to cau se comparable pathology. These results indicate that the E3 region is criti cally involved in modulating the pathogenesis of adenovirus infection and t hat 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-Lu, Only mice lacking both TN FRI and TNFRII were protected from the lethal affects of the mutant adenovi rus. Mice deficient in TNF or TNF and lymphotoxin-cu displayed the fatal pa thology. This outcome is consistent with the existence of another related l igand that binds TNFRI/II to mediate liver damage during infection with thi s mutant.