NIAID Researchers Identify Second Fusion Cofactor for HIV

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The new papers on chemokines and fusion cofactors raise intriguing questions about
the wide variation in the natural history of HIV disease in different individuals, the investigators
note. For instance, does an abundance of RANTES, MIP-lalpha or MIP-Ibeta, or a relative
lack of functional CC CKR5 and related molecules, explain why some individuals have not
become infected with HIV, despite repeated exposure to the virus? A number of NIAIDsupported groups are working to answer this and other important questions.
The identification of two fusion cofactors suggests an immediate practical application:
the production of a small animal model for study of HIV-1 infection. Such a model would be a
potentially valuable tool for developing anti-HIV drugs and vaccines.
"Transgenic animals expressing human CD4 have been developed, but they support
HIV-1 replication poorly," explains Dr. Berger. "Transgenic animals expressing fusin and CC
CKR5 in addition to CD4 may be more useful."
Dr. Berger is chief of the molecular structure section of NIAID's Laboratory of Viral
Diseases (LVD); Dr. Murphy is a senior investigator in NIAID's Laboratory of Host Defenses
(LHD). Their co-authors include, from the LVD, Ghalib Alkhatib, Ph.D., Yu Feng, Ph.D.,
Christopher C. Broder, Ph.D., and Paul Kennedy; and Christophe Combadiere, Ph.D., of the
LHD.
MIAID is a component of the National lnstitutes of Health (NIH). NIAID conducts and
supports research to prevent, diagnose and treat illnesses such as AIDS and other sexually
transmitted diseases, tuberculosis, asthma and allergies. NIH is an agency of the U.S. Public
Health Service, U.S. Department of Health and Human Services.
Reference:

Alkhatib G, Combadiere C, Broder CC, Feng Y, Kennedy PM, Murphy PM, Berger EA.
CC CKR: a RANTES, MIP-lalpha, MIP-1 beta receptor as fusion cofactor for macrophagetropic HIV-1. Science (June 28, 1996).

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