NIH News Release
National Institute of Allergy and
Infectious Diseases

Wednesday, June 17, 1998
2:00 PM Eastern Time

June Wyman
(301) 402-1663

Crystal Structure of Key HIV Protein Reveals New Treatment Targets

In a finding that unlocks new doors to devising drugs and vaccines against HIV, scientists have crystallized the core of gp120, the surface protein molecule that the virus uses to attach itself to immune system cells.

The new model of the gp120 core's crystal structure reveals specific targets for anti-HIV vaccines and drugs, and highlights the surprising array of defenses that the virus uses to evade attack.

"Studying the gp120 crystal's structure can tell us a lot more about how the virus locks on to immune system cells," says Anthony S. Fauci, M.D., director of the National Institute of Allergy and Infectious Diseases (NIAID). "We now have specific target sites on which to focus in developing new drugs and vaccines."

The research, funded in part by NIAID, comes from a team led by Joseph G. Sodroski, M.D., of the Dana-Farber Cancer Institute, Harvard Medical School, Boston, Mass., and Wayne Hendrickson, Ph.D., of Columbia University College of Physicians and Surgeons, New York, N.Y. Their work appears in the June 18, 1998, issue of Nature and the June 19, 1998, issue of Science.

The scientists confirmed several previously known features but also found some surprises in the crystal structure of the protein. "We discovered that a large part of the gp120 surface is protected against attack by a dense array of carbohydrates and by an amazing capacity to change shape," says Dr. Sodroski.

Among their findings were:

The new information on gp120 structure suggests that some current approaches to AIDS vaccines may not work. For example, vaccines based on simple gp120 subunits may not get past gp120's ability to hide its critical binding regions until the last minute. At the same time, the crystal structure reveals vulnerable parts of gp120's architecture that researchers could hone in on to devise new drugs and better vaccine candidates.

"HIV is a viral Houdini," says Dr. Sodroski. "It carries a multiply protected infection machinery that frustrates host defenses. Understanding this machinery should help us target medical interventions to the weak spots in the armor."

The research was funded by NIAID; the National Institute of General Medical Sciences; the Howard Hughes Medical Institute; the American Foundation for AIDS Research; the Aaron Diamond Foundation; the G. Harold and Leila Y. Mathers Foundation; the Friends 10; William McCarty-Cooper; and Douglas and Judi Krupp.

NIAID supports biomedical research to prevent, diagnose and treat illnesses such as AIDS, tuberculosis, malaria, asthma and allergies. NIH is an agency of the U.S. Department of Health and Human Services.

Press releases, fact sheets and other NIAID-related materials are available via the NIAID Web site at


PD Kwong, et al. Structure of an HIV gp120 envelope glycoprotein in complex with the CD4 receptor and a neutralizing human antibody. Nature 393:705-11 (1998).

R Wyatt, et al. The antigenic structure of the human immunodeficiency virus gp120 envelope glycoprotein. Nature 393:648-59 (1998).

C Rizzuto, et al. A conserved HIV gp120 glycoprotein structure involved in chemokine receptor binding. Science 280:1949-53 (1998).