Chemokine receptors have proved to be important in maintaining seronegative status among individuals who have a high risk for contracting the HIV virus. Cultures of lymphocytes and macrophages have shown that those who are relatively resistant to HIV infection secrete high levels of co-receptors CCL3, CCL4, and CCL5 when they are inoculated with this virus. It has been discovered that HIV resistant people are homozygous for an allelic, nonfunctional version of the CCR5 co-receptor, D32. In the Caucasian population, the prevalence of this frameshift mutation (coupled with a protein truncation) in the homozygous form is fairly high at about 1%. The heterozygous allelic form of this mutation may provide some modest protection against the sexual transmission of the HIV virus, and could even slow the progression of existing infections. In addition to this, variation in the promoter region of the CCR5 gene has been identified in both Caucasians and African Americans. Differences in promoter regions have also been associated with different rates of progression of the disease. This evidence shows that CCR5 is the major macrophage and T-lymphocyte co-receptor used by HIV to establish initial infection. Interestingly, this also offers hope that primary HIV infection can be blocked by anti-CCR5 receptors.
Janeway, Charles. Janeway's Immunology - 7th Edition / Kenneth Murphy, Paul Travers, Mark Walport. Garland Science. 2008.
These findings hold the key to a cure for HIV infection, in the form of world-wide eradication. And yet we keep looking for a vaccine. Hello? HIV is a retrovirus -- it explodes DNA and copies itself. I don't think an effective vaccine will ever be found. Certainly not a therapeutic one.
ReplyDeleteI think the allele frequency is closer to 11% than 1% in the Caucasian population.
ReplyDeleteThis same region in the CCR-5 gene has been found associated with Sarcoidoisis which is a disease of unknown cause which leads to an immune response(granuloma formation. I wonder if the anti-CCr5 receptors would help with this diease also, even though they are quite different....
ReplyDeleteHi Lori,
ReplyDeleteDo you have a reference for that? It is very interesting.
Hi Dr. Cohen,
ReplyDeleteThe reference is C-C-Chemokine Receptor 5 Gene variants in relation to lung disease in Sarcoidosis, Spagnolo, Paolo -- Respiratory and Critical Care Medicine Vol 172(2005)
Thanks, Lori!
ReplyDelete