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

Authors

Beatriz Pacheco, Harvard Medical School
Stephane Basmaciogullari, Harvard Medical School
Jason A. LaBonte, Harvard Medical School
Shi-Hua Xiang, University of Nebraska-LincolnFollow
Joseph Sodroski, Harvard Medical SchoolFollow

Date of this Version

1-2008

Comments

JOURNAL OF VIROLOGY, Jan. 2008, p. 346–357 Vol. 82, No. 1 Copyright © 2008, American Society for Microbiology. All Rights Reserved. Used by Permission

Abstract

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-thanoptimal CD4 molecules and provide HIV-1 variants that can overcome some of the early blocks in New World monkey cells.