AIDS: envelope research update.

AIDS: Envelope research update

Two published reports dealing with the structure and function of the AIDS virus, a retrovirus known as HIV, are providing some hope -- and some cautions -- about the possibility of stemming the virus' infectivity.

Researchers at Stanford University Medical Center report in the April 8 CELL that they have inhibited HIV infection in cultured cells by making a minor rearrangement of the HIV envelope protein. The envelope protein, called gp160, is normally cleaved into two pieces during virual replication inside white blood cells. Only after the protein is cleaved into gp120 and gp41 components is the AIDS virus able to bind to and inflect other white blood cells. Under the direction of Joseph M. McCune, the stanford researchers made a specific mutation in the gp160 protein. In doing so, they prevented enzymatic splitting of the protein into its component pieces, rendering the virus biologically inactive.

The research supports the notion that a drug capable of blocking enzymaic splitting of gp160 inside a cell might inhibit HIV's infectivity. Along similar lines, the researchers note, custom-designed antibodies directed against gp41 or gp 120 after enzymatic splitting might also prove effective, since those pieces appear critical to infectivity. Previous research on other retroviruses had suggested such approaches to blocking infectivity might work, but the work had not been done on HIV.

Other research, however, appearing in the April 9 LANCET, strikes a cautionary note for scientists who are developing such antibodies or are developing vaccines that would stimulate the production of such antibodies. Researchers at Vanderbilt University School of Medicine report they have partially characterized two components in HIV-positive blood serum -- one of them apparently an HIV-induced antibody -- that together enhance rather than deter infection by the HIV virus. The researchers reported preliminary evidence of one such factor last year.

In the latest research, the scientists describe the presence of a suspected immunoglobulin that they believe is an antibody to some part of the HIV virus, and a second factor they say is likely to be complement--a biological compound that often interacts with antibodies to destroy cells. Together, they hypothesize, these two factors might work to enhance HIV infection.

It is still not clear which part of the AIDS virus might stimulate the production of such an infection-enhancing antibody, the say, adding that vaccine developers will have to be careful to choose parts of the AIDS virus that will stimulate production of protective antibodies exclusively.

They conclude that if part of the AIDS virus "can be correlated with the induction of antibodies that together with complement enhance HIV-1 infection, then candidate vaccines should obviously be devoid of such antigenic stimuli. Those vaccines already being tested should be evaluated for their ability to stimulate infection-enhancing antibody formation."