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Journal of Virology, July 2001, p. 5812-5822, Vol. 75, No. 13
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.13.5812-5822.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Human Immunodeficiency Virus Type 1 (HIV-1)-Induced GRO-alpha Production Stimulates HIV-1 Replication in Macrophages and T Lymphocytes

Brian R. Lane,1,2 Robert M. Strieter,3,dagger Michael J. Coffey,3 and David M. Markovitz1,2,*

Department of Internal Medicine, Divisions of Infectious Diseases1 and Pulmonary and Critical Care Medicine,3 and Program in Cellular and Molecular Biology,2 University of Michigan Medical Center, Ann Arbor, Michigan 48109-0640

Received 14 November 2000/Accepted 21 March 2001

We examined the early effects of infection by CCR5-using (R5 human immunodeficiency virus [HIV]) and CXCR4-using (X4 HIV) strains of HIV type 1 (HIV-1) on chemokine production by primary human monocyte-derived macrophages (MDM). While R5 HIV, but not X4 HIV, replicated in MDM, we found that the production of the C-X-C chemokine growth-regulated oncogene alpha (GRO-alpha ) was markedly stimulated by X4 HIV and, to a much lesser extent, by R5 HIV. HIV-1 gp120 engagement of CXCR4 initiated the stimulation of GRO-alpha production, an effect blocked by antibodies to CXCR4. GRO-alpha then fed back and stimulated HIV-1 replication in both MDM and lymphocytes, and antibodies that neutralize GRO-alpha or CXCR2 (the receptor for GRO-alpha ) markedly reduced viral replication in MDM and peripheral blood mononuclear cells. Therefore, activation of MDM by HIV-1 gp120 engagement of CXCR4 initiates an autocrine-paracrine loop that may be important in disease progression after the emergence of X4 HIV.

* Corresponding author. Mailing address: 5220 MSRB III, 1150 West 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, July 2001, p. 5812-5822, Vol. 75, No. 13
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.13.5812-5822.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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