Increased Neutralization Sensitivity of CD4-Independent Human Immunodeficiency Virus Variants

doi:10.1128/JVI.75.5.2041-2050.2001

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Journal of Virology, March 2001, p. 2041-2050, Vol. 75, No. 5
0022-538X/01/$04.00+0 DOI: 10.1128/JVI.75.5.2041-2050.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Increased Neutralization Sensitivity of CD4-Independent Human Immunodeficiency Virus Variants

Peter Kolchinsky,¹ Enko Kiprilov,¹ and Joseph Sodroski¹^,²^,^*

Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, and Department of Pathology, Harvard Medical School,¹ and Department of Immunology and Infectious Diseases, Harvard School of Public Health,² Boston, Massachusetts 02115

Received 21 July 2000/Accepted 1 December 2000

Naturally occurring human immunodeficiency virus (HIV-1) variants require the presence of CD4 and specific chemokine receptorsto enter a cell. In the laboratory, HIV-1 variants that are capableof bypassing CD4 and utilizing only the CCR5 chemokine receptorfor virus entry have been generated. Here we report that theseCD4-independent viruses are significantly more sensitive to neutralizationby soluble CD4 and a variety of antibodies. The same amino acidchanges in the HIV-1 gp120 envelope glycoprotein determined CD4independence and neutralization sensitivity. The CD4-independentenvelope glycoproteins exhibited higher affinity for antibodiesagainst CD4-induced gp120 epitopes but not other neutralizingligands. The CD4-independent envelope glycoproteins did not exhibitincreased lability relative to the wild-type envelope glycoproteins.The utilization of two receptors apparently allows HIV-1 to maintaina more neutralization-resistant state prior to engaging CD4 onthe target cell, explaining the rarity of CD4 independence inwild-type HIV-1.

^* Corresponding author. Mailing address: Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, 44 Binney St.,JFB 824, Boston, MA 02115. Phone: (617) 632-3371. Fax: (617) 632-4338.E-mail: joseph_sodroski{at}dfci.harvard.edu.

Journal of Virology, March 2001, p. 2041-2050, Vol. 75, No. 5
0022-538X/01/$04.00+0 DOI: 10.1128/JVI.75.5.2041-2050.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

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