HIV regulation of the IL-7R: a viral mechanism for enhancing HIV-1 replication in human macrophages in vitro

Journal of Leukocyte Biology

Mingjie Zhang⁴  David M. Frucht¹  Andrew I. Dayton⁴  Carla S. R. Lankford¹  Franziska Schwartzkopff¹  Kathleen A. Clouse¹  Thomas R. Gingeras²  Chettemegre Venkateshan⁴  Ronald L. Rabin³  Jorg Drenkow² 

[1] Division of Monoclonal Antibodies, Office of Biotechnology Products, Center for Drug Evaluation and Research, Bethesda, Maryland Division of Monoclonal Antibodies, Office of Biotechnology Products, Center for Drug Evaluation and Research, Bethesda, Maryland Division of Monoclonal Antibodies, Office of Biotechnology Products, Center for Drug Evaluation and Research, Bethesda, Maryland;Affymetrix, Santa Clara, California; and Affymetrix, Santa Clara, California; and Affymetrix, Santa Clara, California; andLaboratory of Immunobiochemistry, DBPAP, Office of Vaccine Research and Review, Center for Biologics Evaluation & Research, U.S. Food and Drug Administration, Rockville, Maryland; Laboratory of Immunobiochemistry, DBPAP, Office of Vaccine Research and Review, Center for Biologics Evaluation & Research, U.S. Food and Drug Administration, Rockville, Maryland; Laboratory of Immunobiochemistry, DBPAP, Office of Vaccine Research and Review, Center for Biologics Evaluation & Research, U.S. Food and Drug Administration, Rockville, Maryland;;Laboratory of Molecular Virology, Division of Emerging and Transfusion Transmitted Diseases, Office of Blood Research & Review, and Laboratory of Molecular Virology, Division of Emerging and Transfusion Transmitted Diseases, Office of Blood Research & Review, and Laboratory of Molecular Virology, Division of Emerging and Transfusion Transmitted Diseases, Office of Blood Research & Review, and

关键词: cytokine receptors;    cytokines;    Tat;    AIDS;   

DOI  :  10.1189/jlb.0704424

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

We report a novel mechanism, involving up-regulation of the interleukin (IL)-7 cytokine receptor, by which human immunodeficiency virus (HIV) enhances its own production in monocyte-derived macrophages (MDM) in vitro. HIV-1 infection or treatment of MDM cultures with exogenous HIV-1 Tat(86) protein up-regulates the IL-7 receptor (IL-7R) α-chain at the levels of steady-state RNA, protein, and functional IL-7R on the cell surface (as measured by ligand-induced receptor signaling). This IL-7R up-regulation is associated with increased amounts of HIV-1 virions in the supernatants of infected MDM cultures treated with exogenous IL-7 cytokine. The overall effect of IL-7 stimulation on HIV replication in MDM culture supernatants is typically in the range of one log and greater. The results are consistent with a model in which HIV infection produces the Tat protein, which in turn up-regulates IL-7R in a paracrine manner. This results in increased IL-7R signaling in response to the IL-7 cytokine, which ultimately promotes early events in HIV replication, including binding/entry and possibly other steps prior to reverse transcription. The results suggest that the effects of IL-7 on HIV replication in MDM should be considered when analyzing and designing clinical trials involving treatment of patients with IL-7 or Tat vaccines.

【 授权许可】

Unknown