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J Virol. 2002 Nov;76(22):11710-4.

Elevated levels of tumor necrosis factor alpha (TNF-alpha) in human immunodeficiency virus type 1-transgenic mice: prevention of death by antibody to TNF-alpha.

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1
Experimental Medicine Section, Oral Infection and Immunity Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, Maryland 20892, USA.

Abstract

Homozygous human immunodeficiency virus type 1 (HIV-1)-transgenic mice (Tg26) appear normal at birth but die within 3 to 4 weeks. The skin of these animals shows diffuse scaling and high-level expression of both HIV-1 mRNA and gp120. Previous experiments showed that treatment with human chorionic gonadatropin (hCG) prevented death and the expression of HIV-1 mRNA and gp120. The present experiments were initiated to study the role of tumor necrosis factor alpha (TNF-alpha) in HIV-1-induced pathology. Examination of the sera of Tg26 mice revealed a 50-fold increase in TNF-alpha levels compared to those in nontransgenic mice. Treatment with antibody to TNF-alpha prevented death, resulted in near normal growth, and produced a marked decrease in skin lesions and a profound reduction in the expression of HIV-1 mRNA and gp120. Both TNF-alpha antibody and hCG reduced TNF-alpha levels in sera by approximately 75%. We conclude that TNF-alpha contributes in a major way to HIV-1-induced pathology in transgenic mice and that both hCG and antibody to TNF-alpha prevent the development of pathology by suppressing the level of TNF-alpha.

PMID:
12388730
PMCID:
PMC136749
[Indexed for MEDLINE]
Free PMC Article
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