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Genetic and functional analysis of R5X4 human immunodeficiency virus type 1 envelope glycoproteins derived from two individuals homozygous for the CCR5delta32 allele.

Gray L, Churchill MJ, Keane N, Sterjovski J, Ellett AM, Purcell DF, Poumbourios P, Kol C, Wang B, Saksena NK, Wesselingh SL, Price P, French M, Gabuzda D, Gorry PR

Macfarlane Burnet Institute for Medical Research and Public Health, GPO Box 2284, Melbourne 3001, Victoria, Australia.

We characterized human immunodeficiency virus type 1 (HIV-1) envelope glycoproteins (Env) isolated from two HIV-1-infected CCR5delta32 homozygotes. Envs from both subjects used CCR5 and CXCR4 for entry into transfected cells. Most R5X4 Envs were lymphocyte-tropic and used CXCR4 exclusively for entry into peripheral blood mononuclear cells (PBMC), but a subset was dually lymphocyte- and macrophage-tropic and used either CCR5 or CXCR4 for entry into PBMC and monocyte-derived macrophages. The persistence of CCR5-using HIV-1 in two CCR5delta32 homozygotes suggests the conserved CCR5 binding domain of Env is highly stable and provides new mechanistic insights important for HIV-1 transmission and persistence.

Published 15 March 2006 in J Virol, 80(7): 3684-91.
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