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Journal of Virology, January 2008, p. 346-357, Vol. 82, No. 1
0022-538X/08/$08.00+0     doi:10.1128/JVI.01299-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Adaptation of the Human Immunodeficiency Virus Type 1 Envelope Glycoproteins to New World Monkey Receptors

Beatriz Pacheco,¹ Stephane Basmaciogullari,^1, Jason A. LaBonte,¹ Shi-Hua Xiang,¹ and Joseph Sodroski^1,2*

Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, and Department of Pathology, Division of AIDS, Harvard Medical School, Boston, Massachusetts 02115,¹ Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, Massachusetts 02115²

Received 16 June 2007/ Accepted 11 October 2007

Human immunodeficiency virus type 1 (HIV-1) infection encounters an early block in the cells of New World monkeys because the CD4 receptor does not efficiently support HIV-1 entry. We adapted HIV-1(NL4-3) and HIV-1(KB9), two HIV-1 variants with different envelope glycoproteins, to replicate efficiently in cells expressing the CD4 and CXCR4 proteins of the common marmoset, a New World monkey. The HIV-1(NL4-3) adaptation involves three gp120 changes that result in a specific increase in affinity for the marmoset CD4 glycoprotein. The already high affinity of the HIV-1(KB9) envelope glycoproteins for marmoset CD4 did not significantly change as a result of the adaptation. Instead, changes in the gp120 variable loops and gp41 ectodomain resulted in improved replication in cells expressing the marmoset receptors. HIV-1(KB9) became relatively sensitive to neutralization by soluble CD4 and antibodies as a result of the adaptation. These results demonstrate the distinct mechanistic pathways by which the HIV-1 envelope glycoproteins can adapt to less-than-optimal CD4 molecules and provide HIV-1 variants that can overcome some of the early blocks in New World monkey cells.

Published ahead of print on 24 October 2007.

Present address: Institut Cochin, Département des Maladies Infectieuses, INSERM U567, CNRS UMR 8104 and Université Paris V, 75014 Paris, France.