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J Virol. 2008 Jan;82(1):346-57. Epub 2007 Oct 24.

Adaptation of the human immunodeficiency virus type 1 envelope glycoproteins to new world monkey receptors.

Author information

1
Dana-Farber Cancer Institute, 44 Binney Street, JFB 824, Boston, MA 02115, USA.

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

PMID:
17959679
PMCID:
PMC2224371
DOI:
10.1128/JVI.01299-07
[Indexed for MEDLINE]
Free PMC Article
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