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Curr Opin HIV AIDS. 2009 Mar;4(2):96-103. doi: 10.1097/COH.0b013e328324bbec.

The biology of CCR5 and CXCR4.

Author information

1
Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN 46202, USA. galkhati@iupui.edu

Abstract

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.

PMID:
19339947
PMCID:
PMC2718543
DOI:
10.1097/COH.0b013e328324bbec
[Indexed for MEDLINE]
Free PMC Article

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