Adenovirus-induced liver pathology is mediated through TNF receptors I and II but is independent of TNF or lymphotoxin

H Hayder; R V Blanden; H Körner; D S Riminton; J D Sedgwick; A Müllbacher

Adenovirus-induced liver pathology is mediated through TNF receptors I and II but is independent of TNF or lymphotoxin

J Immunol. 1999 Aug 1;163(3):1516-20.

Authors

H Hayder¹, R V Blanden, H Körner, D S Riminton, J D Sedgwick, A Müllbacher

Affiliation

¹ Division of Immunology, John Curtin School of Medical Research, Australian National University, Canberra.

PMID: 10415054

Abstract

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.

MeSH terms

Adenoviridae Infections / immunology*
Adenoviridae Infections / pathology*
Adenoviridae Infections / virology
Adenoviruses, Human / genetics
Adenoviruses, Human / immunology
Animals
Antigens, CD / genetics
Antigens, CD / metabolism
Antigens, CD / physiology*
DNA, Viral / analysis
Female
Humans
Immunity, Innate
Liver / immunology*
Liver / pathology*
Liver / virology
Lymphotoxin-alpha / genetics
Lymphotoxin-alpha / physiology*
Mice
Mice, Inbred C3H
Mice, Inbred C57BL
Mice, Inbred CBA
Mice, Knockout
Polymerase Chain Reaction
Receptors, Tumor Necrosis Factor / genetics
Receptors, Tumor Necrosis Factor / metabolism
Receptors, Tumor Necrosis Factor / physiology*
Receptors, Tumor Necrosis Factor, Type I
Receptors, Tumor Necrosis Factor, Type II
Tumor Necrosis Factor-alpha / deficiency
Tumor Necrosis Factor-alpha / genetics
Tumor Necrosis Factor-alpha / physiology*

Substances

Antigens, CD
DNA, Viral
Lymphotoxin-alpha
Receptors, Tumor Necrosis Factor
Receptors, Tumor Necrosis Factor, Type I
Receptors, Tumor Necrosis Factor, Type II
Tumor Necrosis Factor-alpha