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Journal of Virology, September 2001, p. 8842-8847, Vol. 75, No. 18
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.18.8842-8847.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Cytopathicity of Human Immunodeficiency Virus Type 1 Primary Isolates Depends on Coreceptor Usage and Not Patient Disease Status

Jason F. Kreisberg,1,2 David Kwa,3,4 Birgit Schramm,1,dagger Verena Trautner,1,Dagger Ruth Connor,5 Hanneke Schuitemaker,3,4 James I. Mullins,6 Angélique B. van't Wout,6 and Mark A. Goldsmith1,7,*

Gladstone Institute of Virology and Immunology1 and Departments of Physiology2 and Medicine,7 University of California, San Francisco, California 94141-9100; Department of Clinical Viro-Immunology, Central Laboratory of The Netherlands Red Cross Blood Transfusion Service,3 and Laboratory for Experimental and Clinical Immunology, University of Amsterdam,4 Amsterdam, The Netherlands; Aaron Diamond AIDS Research Center, Rockefeller University, New York, New York 100165; and Department of Microbiology, University of Washington School of Medicine, Seattle, Washington 98195-77406

Received 28 March 2001/Accepted 8 June 2001

It has been hypothesized that human immunodeficiency virus type 1 (HIV-1) evolves toward increased cytopathicity in conjunction with disease progression in infected patients. A viral property known to evolve in some but not all patients is coreceptor utilization, and it has been shown that a switch in coreceptor utilization is sufficient for the development of increased cytopathicity. To test the hypothesis that the evolution of other viral properties also contributes to accelerating cytopathicity in vivo, we used human lymphoid tissue explants to assay the cytopathicity of a panel of primary HIV-1 isolates derived from various stages of disease characterized by the presence or absence of changes in coreceptor preference. We found no evidence of coreceptor-independent increases in cytopathicity in isolates obtained either before coreceptor preference changes or from patients who progressed to AIDS despite an absence of coreceptor evolution. Instead, the cytopathicity of all HIV-1 isolates was determined solely by their coreceptor utilization. These results argue that HIV-1 does not evolve toward increased cytopathicity independently of changes in coreceptor utilization.

* Corresponding author. Mailing address: Gladstone Institute of Virology and Immunology, P.O. Box 419100, San Francisco, CA 94141-9100. Phone: (415) 695-3775. Fax: (415) 695-1364. E-mail: mgoldsmith{at}gladstone.ucsf.edu.

dagger Present address: Department of Virology, University of the Saarland Medical School, Homburg-Saar, Germany.

Dagger Present address: Institute of Medical Microbiology and Hygiene, University of Regensburg, Regensburg, Germany.

Journal of Virology, September 2001, p. 8842-8847, Vol. 75, No. 18
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.18.8842-8847.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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