Human Immunodeficiency Virus (HIV), the cause of AIDS, infects CD4+ T lymphocytes and cells of the monocyte/macrophage lineage through binding to CD4 molecules on the surface of these cells. The glycoprotein (gp) 120 on the surface of the HIV particle is responsible for the binding (see below).
It is now apparent that accessory molecules on the surface of the CD4+ cells are involved in allowing the penetration of HIV into the cell. CD4 molecules are known to play a central role (frame B), but the chemokine receptors, CXCR4 (fusin) and CCR5 are also involved, possibly by removing gp120 from the HIV particle, thus exposing gp41, which is necessary for the membrane attachment of HIV (frame C) and the transfection of the lymphocyte (frame D).
The C-X-C chemokine SDF-1 (Stromal-Derived Factor-1) and the C-C chemokines RANTES (Regulated upon Activation, Normal T cell Expressed and Secreted), and MIP-1a and -1b (Macrophage Inflammatory Protein-1a and 1b) are effective in blocking HIV infection in vitro.
IIR is particularly interested in searching for mechanisms of regulation of the various components of the chemokine systems in normal and in HIV-infected individuals.
