Blocking HIV co-receptors by chemokines

Specific chemokines can block HIV entry and replication because they antagonize the common strategy of lentiviruses to use chemokine receptors for infecting CD4+ cells of the body, especially lymphocytes and cells of the monocytic lineage. This raised intense academical and therapeutical interest. The antiviral potency of these chemokines is indeed remarkable, but depends on the chemokine and the HIV isolate used. This is because HIV appears to use many co-receptors, alternatively or in addition to the CCR5 co-receptor. These include CCR3, CXCR4, STRL33/Bonzo/TYMSTR, and BOB. The CC chemokines RANTES, MIP-1alpha, MIP-1beta, and Eotaxin can suppress the replication of CCR5- and CCR3-dependent viruses, while SDF-1 alpha/beta suppresses that of CXCR4-dependent strains. Although no general rule can be drawn at present, it appears that chronic HIV infection may give rise to viruses which, instead of using preferentially or exclusively CCR5, are capable of using more than one co-receptor. This underlines the need for assaying the tropism of primary isolates, using both fusion assays and protection of activated lymphocyte cultures by one or more antiviral chemokines or chemokine antagonists.