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


RESULTS
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.


CONCLUSIONS
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.
Alkhatib
Ghalib
G
Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN 46202, USA. galkhati@iupui.edu