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Journal of Virology, November 2002, p. 11710-11714, Vol. 76, No. 22
0022-538X/02/$04.00+0 DOI: 10.1128/JVI.76.22.11710-11714.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.
) in Human Immunodeficiency Virus Type 1-Transgenic Mice: Prevention of Death by Antibody to TNF-
Krishnakumar Devadas, and Abner Louis Notkins*
Experimental Medicine Section, Oral Infection and Immunity Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, Maryland 20892
Received 27 March 2002/ Accepted 1 August 2002
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-
) in HIV-1-induced pathology. Examination of the sera of Tg26 mice revealed a 50-fold increase in TNF-
levels compared to those in nontransgenic mice. Treatment with antibody to TNF-
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-
antibody and hCG reduced TNF-
levels in sera by approximately 75%. We conclude that TNF-
contributes in a major way to HIV-1-induced pathology in transgenic mice and that both hCG and antibody to TNF-
prevent the development of pathology by suppressing the level of TNF-
.
Present address: Center for Drugs Evaluation and Research, Food and Drug Administration, Rockville, MD 20857-0001.
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