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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 CCR5{Delta}32 Allele

Lachlan Gray,1,2 Melissa J. Churchill,1 Niamh Keane,3,4 Jasminka Sterjovski,1,5 Anne M. Ellett,1 Damian F. J. Purcell,2 Pantelis Poumbourios,1 Chenda Kol,6 Bin Wang,6 Nitin K. Saksena,6 Steven L. Wesselingh,1,5 Patricia Price,3,4 Martyn French,3,4 Dana Gabuzda,7,8 and Paul R. Gorry1,2,5*

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 CCR5{Delta}32 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 CCR5{Delta}32 homozygotes suggests the conserved CCR5 binding domain of Env is highly stable and provides new mechanistic insights important for HIV-1 transmission and persistence.

* Corresponding author. Mailing address: Macfarlane Burnet Institute for Medical Research and Public Health, GPO Box 2284, Melbourne 3001, Victoria, Australia. Phone: 61-3-9282-2129. Fax: 61-3-9282-2100. E-mail: gorry{at}burnet.edu.au.

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.



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