NIAID Researchers Identify Second Fusion Cofactor for HIV

86/14/96 14:48 iED I ATEL FAX SERVICE->SCIENCE (FREELANCE)/JON COHEN 882
JUN-14-1996 17:29 N IAID 301 402 0120 P.03
2
HIV-1 preferentially infect macrophages in cell culture experiments. These isolates are the
main strains found in patients during the symptom-free stage of HIV disease, which may last for
many years.
Previously, Dr. Berger and his group demonstrated that fusin acts as a cofactor for the
entry of T-cell line-tropic HIV-1 isolates into immune system cells: these strains tend to appear
later in infected people, coincident with the decline of the immune system.
"Together with the recent identification by the Berger group of the receptor for T celltropic strains of HIV-1, the current identification of CC CKR5 as the receptor for macrophagetropic strains of HIV adds considerably to our understanding of the mechanisms whereby HIV
infects its target cells," comments Anthony S. Fauci, M.D., NIAID director. "This information
should prove extremely useful in the delineation of pathogenesis of HIV infection and should
serve as a basis for designing new therapeutic strategies."
In addition to its role in fusion, CC CKR5 is a receptor for certain immune-signalling
molecules - RANTES, MIP-lalpha and MlP-1beta -- that are known to suppress HIV infection
of cells. These three molecules belong to a family of molecules called chemokines involved in
the body's inflammatory response.
"When considered with recent data from other groups, our new findings suggest that
one mechanism by which RANTES, MIP-lalpha and MIP-1 beta suppress lHIV infectivity is by
blocking the process of fusion used by the virus to enter cells," says Dr. Berger.
The researchers note that other groups have suggested that chemokines might be used
therapeutically. "These new data provide a molecular explanation for the suppression of HIV
infectivity by chemokines, and suggest that fusion cofactors may provide a potential target for

rational drug design," says Dr. Murphy.

(more)