| | Re: Hiv
In my work "Analysis of HTLV-I, HIV, and HBsAg in 1200 blood donors" presented in Human Retroviruses Congress, Genoa - November 9-11 1992, and published under the Medical Systems Genoa imprint in Pandora Journal, 75-79, Sept-Dec 1993, in which were presented the central mimicry mechanism for the entry of HIV virus in specific target cells. This process is mediated by the trimeric envelope glycoprotein complex, which consists of three gp120 exterior envelope glycoproteins and three gp41 transmembrane envelope glycoproteins, and CD4 receptor on the surface of a new potential host cell. Binding of gp120 to the CD4 receptor induces major conformational changes in the envelope glycoproteins that undergoes a remarkable refolding, exposing cryptic epitopes on gp120 that stabilize the CD4 interactions. These changes allow gp120 to bind the viral coreceptor, either CXCR4 or CCR5. CD4 binding also induces the formation of a gp41 pre-hairpin intermediate, in which three hydrophobic grooves on the surface of a coiled coil formed by the heptad repeat 1 (HR1) region of gp41 are exposed. These hydrophobic grooves are subsequently occupied by helices from the gp41 heptad repeat 2 (HR2) region, during the formation of an energetically stable six-helix bundle that is thought to drive the fusion of the viral and target cell membranes and following this “short living activated infective virus” entry in the host cell. This last phenomenon has been in vitro confirmed mixing receptor sCD4 (soluble CD4) with HIV-1 virus that suffers a phase of transitory activation during which the virus attachment to the cells that express CCR5 will allow entry to occur. This activated state is short-lived and is followed by apparently irreversible structural rearrangements and “loss of infectivity”. Thus, at any given time point after exposure to sCD4, HIV-1 infectivity represents the combined result of an activation process and progression through the activated intermediate state to inactivation.
The knowledges on the CD4 receptor structure has allowed to produce a proteinaceous chimeric receptor that comprising : a) an portion which includes a fragment of CD4 which is capable of specifically recognizing and binding the HIV-infected cell expressing HIV envelope proteins and b) an portion which is capable of signalling at an therapeutic cell to destroy the receptor-bound HIV-infected cell. Isofar, this chimeric receptor have two bound points, both fragment that recognize HIV-infected cells and fragment that bound to T-cytotoxic or B-cells receptor or at Fc receptor subunits which are capable of directing immune cell to recognize and lyse HIV-infected cells.