WASHINGTON -- What separates the long-term survivors withHIV from those who succumb to AIDS? Lack of a single aminoacid change and a lot of CD8 cells, Jay Levy, professor ofmedicine at the Cancer Research Institute of the University ofCalifornia, San Francisco, told an audience Monday at theannual meeting of the American Federation for ClinicalResearch here.

The virus goes through three stages of response to the patient'santibodies. In the first stage, antibodies neutralize the virus.Then the virus becomes resistant to antibodies. Finally, theantibodies actually enhance viral replication.

Each change is marked by the change of a single amino acid inthe epitope on the so-called V3 loop of the virus. Using site-directed mutagenesis. Levy's colleague, research virologistSrisakul Kliks, re-created the change in the virus fromantibody-susceptible to antibody-resistant.

The mechanism for enhancement is simple, Kliks explained. Thesecond change in the variable amino acid enables the virus tocomplex with the antibody, which alters its shape so that it canenter through the back door, as it were -- the so-called Fcreceptor.

In one patient, who was healthy when first examined in 1986and who developed AIDS-related complex (ARC) in 1989, thevirus became resistant to antibodies in 1988. In 1989, Levyfound in in vitro experiments that viral replication wasenhanced 300 percent by serum antibodies.

Oddly enough, however, blood serum from U.S. patients thatneutralized two U.S. strains of HIV enhanced a strain that hadbeen obtained from a patient in Africa.

"The message is that the overall conformation determines thevirus' ability to enter and kill the cell," said Levy.

Following suggestive observations in patients, Levy's colleagueChris Walker found that CD8 cells would suppress viralreplication in vitro, but that when the CD8 cells were removed,replication would resume. Levy's group has now isolated areplication-suppressing factor from CD8 cells, which has not yetbeen identified.

Just prior to onset of illness, the number of CD8 cells drops,followed "some time later" by decline in CD4 cells, said Levy. Asfor long-term survivors, "They have non-virulent virus strains,absence of enhancing antibodies and strong CD8 response."

"We hope to (be able to use the CD8 factor) to arrest replicationof the virus that gives rise to the virulent and pathogenicstrains," Levy said.

-- David C. Holzman Washington Editor

(c) 1997 American Health Consultants. All rights reserved.