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Journal of Virology, September 2001, p. 8195-8202, Vol. 75, No. 17
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.17.8195-8202.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Interleukin-8 Stimulates Human Immunodeficiency Virus Type 1 Replication and Is a Potential New Target for Antiretroviral Therapy

Brian R. Lane,1,2 Karin Lore,3 Paul J. Bock,1,2 Jan Andersson,4 Michael J. Coffey,5 Robert M. Strieter,5,dagger and David M. Markovitz1,2,*

Divisions of Infectious Diseases1 and Pulmonary and Critical Care Medicine,5 Department of Internal Medicine, and Graduate Program in Cellular and Molecular Biology,2 University of Michigan Medical Center, Ann Arbor, Michigan 48109-0640, and Department of Microbiology, Pathology and Immunology3 and Department of Medicine, Center for Infectious Medicine,4 Karolinska Institutet, Stockholm, Sweden

Received 25 January 2001/Accepted 21 May 2001

Production of the C-X-C chemokines interleukin-8 (IL-8) and growth-regulated oncogene alpha (GRO-alpha ) in macrophages is stimulated by exposure to human immunodeficiency virus type 1 (HIV-1). We have demonstrated previously that GRO-alpha then stimulates HIV-1 replication in both T lymphocytes and macrophages. Here we demonstrate that IL-8 also stimulates HIV-1 replication in macrophages and T lymphocytes. We further show that increased levels of IL-8 are present in the lymphoid tissue of patients with AIDS. In addition, we demonstrate that compounds which inhibit the actions of IL-8 and GRO-alpha via their receptors, CXCR1 and CXCR2, also inhibit HIV-1 replication in both T lymphocytes and macrophages, indicating potential therapeutic uses for these compounds in HIV-1 infection and AIDS.

* Corresponding author. Mailing address: 5220 MSRB III, 1150 W. Medical Center Dr., Ann Arbor, MI 48109-0640. Phone: (734) 647-1786. Fax: (734) 764-0101. E-mail: dmarkov{at}umich.edu.

dagger Present address: Department of Medicine, Division of Pulmonary and Critical Care Medicine, UCLA School of Medicine, Los Angeles, CA 90095-1922.

Journal of Virology, September 2001, p. 8195-8202, Vol. 75, No. 17
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.17.8195-8202.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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