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The biology of CCR5 and CXCR4

Alkhatib, Ghalib

Current Opinion in HIV and AIDS: March 2009 - Volume 4 - Issue 2 - p 96–103
doi: 10.1097/COH.0b013e328324bbec
Entry inhibitors: Edited by Jose A. Esté

Purpose of review We discuss the current knowledge concerning the biology of CXCR4 and CCR5 and their roles in HIV-1 infection.

Recent findings Important research findings reported in the last 2 years have advanced our knowledge in the field of HIV coreceptors and pathogenesis. Novel methods have been used to crystallize two new members of the G-protein coupled receptors. It has been demonstrated that expression and stability of the naturally occurring truncated CCR5 protein is critical for resistance to HIV-1. The first stem cell transplantation of donor cells with the CCR5 mutation provided proof of principle. The Food and Drug Administration approved the first CCR5-based entry inhibitor. New CXCL12 isoforms were discovered, one isoform is a potent X4 inhibitor with weak chemotaxis activity.

Summary The coreceptor discoveries revealed new insights into host and viral factors influencing HIV transmission and disease. The HIV/coreceptor interaction has become a major target for the development of novel antiviral strategies to treat and prevent HIV infection. The first CCR5-based entry inhibitor has been recently approved. New drugs that promote CCR5 and CXCR4 internalization, independent of cellular signaling, might provide clinical benefits with minimum side effects.

Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, Indiana, USA

Correspondence to Ghalib Alkhatib, Department of Microbiology and Immunology, Medical Sciences Building, Room 420, 635 Barnhill Drive, Indianapolis, IN 46202, USA Tel: +1 317 278 3698; fax: +1 317 274 4090; e-mail:

© 2009 Lippincott Williams & Wilkins, Inc.