Saturday, November 25, 2006

Chemokine levels influence virus infection

drj writes "HIV-1 infects cells by binding to CCR5, a cell surface receptor for the immune-signaling protein (chemokine) CCL3L1 (MIP-1alpha). One allele (version) of the CCR5 gene has a 32-bp deletion (CCR5delta32). People with two copies of CCR5delta32 are relatively resistant to HIV-1 infection and even one copy delays progression to AIDS. A relatively high frequency of the CCR5delta32 allele in people of European origin (10%) might be due to selection by plague or hemorrhagic fever. Now, Gonzalez and colleagues show that variation in the copies of the gene encoding CCL3L1 is also important. People with more copies of the CCL3L1 gene are more resistant to HIV and AIDS. (This correlation may not hold in some populations.) The simple explanation is that CCL3L1 competes with HIV-1 for binding to CCR5. It's surprising that a receptor can be occupied enough to make a difference. CCR5 is already a target for therapy with small molecule inhibitors. Unfortunately, HIV-1 has demonstrated its ability to develop resistance to some small molecule inhibitors of CCR5.
PubMed Gonzalez et al. Science. 2005 307(5714):1434-40. The influence of CCL3L1 gene-containing segmental duplications on HIV-1/AIDS susceptibility.

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