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Journal of Virology, April 2006, p. 3684-3691, Vol. 80, No. 7
0022-538X/06/$08.00+0     doi:10.1128/JVI.80.7.3684-3691.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Genetic and Functional Analysis of R5X4 Human Immunodeficiency Virus Type 1 Envelope Glycoproteins Derived from Two Individuals Homozygous for the CCR532 Allele

The Macfarlane Burnet Institute for Medical Research and Public Health, Melbourne, Victoria, Australia,¹ Department of Microbiology and Immunology, University of Melbourne, Melbourne, Victoria, Australia,² Department of Clinical Immunology and Biochemical Genetics, Royal Perth Hospital, Perth, Western Australia, Australia,³ School of Surgery and Pathology, University of Western Australia, Perth, Western Australia, Australia,⁴ Department of Medicine, Monash University, Melbourne, Victoria, Australia,⁵ Westmead Millennium Institute, Westmead, New South Wales, Australia,⁶ Dana-Farber Cancer Institute, Boston, Massachussets,⁷ Department of Neurology, Harvard Medical School, Boston, Massachussets⁸

Received 18 December 2005/ Accepted 12 January 2006

We characterized human immunodeficiency virus type 1 (HIV-1) envelope glycoproteins (Env) isolated from two HIV-1-infected CCR532 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 CCR532 homozygotes suggests the conserved CCR5 binding domain of Env is highly stable and provides new mechanistic insights important for HIV-1 transmission and persistence.

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