Attempts to use the CD4 molecule as an AIDS therapy havebeen foiled by the fact that something in the serum of infectedpeople blocks CD4's ability to find and bind to the virus. ButTexas scientists have successfully altered the molecule tocircumvent this obstacle to a CD4-based AIDS therapy.
As described in the July issue of the Proceedings of theNational Academy of Sciences, researchers at the University ofTexas Southwestern Medical Center in Dallas have linked CD4to a big protein called ovalbumen, the sheer bulk of whichprevents antibodies from blocking the viral target.
Previous reports have disputed whether serum from infectedindividuals does in fact interfere with CD4, a molecule thatrecognizes the gp120 surface protein of the virus. But thediscrepancies can be explained, the researchers report. Twotypes of antibodies from HIV-positive people exist, and onlyone type seems to stick to and block access to gp120.
The Texas researchers synthesized portions of the CD4molecule from peptides, hitched each to ovalbumen and pickedthe one most potent in binding gp120. This CD4-ovalbumencombination was able to bind recombinant gp120 protein intest tubes despite the presence of HIV-positive serum.
The interfering antibodies in the HIV-positive serum probablybind at a site near the CD4 site on gp120. Ovalbumen hangingoff the modified CD4 covers this antibody site, protectingaccess for CD4, the researchers postulate.
Because ovalbumen is antigenic, the researchers have nowlinked CD4 with human serum albumen, said Victor Ghetie, aresearcher with the university's Cancer Immunobiology Center.This human protein will stay in the body for several days,Ghetie said.
The researchers are interested in finding corporate sponsorsto help develop the linked CD4 as an AIDS treatment. "There'sno future for CD4 itself," Ghetie told BioWorld.070891CD4
-- Roberta Friedman, Ph.D. Special to BioWorld
(c) 1997 American Health Consultants. All rights reserved.