Important note: Information in this article was accurate in May 1999. The state of the art may have changed since the publication date.AIDSWEEKLY Plus; Monday, May 3, 1999
Daniel J. DeNoon, Senior Editor
Recent studies appeared to find a weak spot in HIV's defenses: its ability to infect cells was linked to a bridge between the inner and outer domains of its envelope that is conserved across many viral strains (Rizzuto, C. et al., Science 1998 Jun 19;280(5371):1949-53 and Wyatt, R. et al., Nature 1998 Jun 18;393(6686):705-11.
This region, it was hoped, would serve as the target for anti-HIV drugs or as an antigen for HIV vaccines. But new studies show that hypervariable residues participate in the CCR5-coreceptor-binding interactions mediated by the target region.
"Although the highly conserved V3 residues may represent unique targets for antiviral designs, the involvement of variable residues raises the possibility that antigenic variation in the coreceptor binding domain could further complicate HIV-1 vaccine design," wrote Harvard researchers Wei-Kung Wang and colleagues.
Wang et al. reported their studies in the Proceedings of the National Academy of Sciences ("Hypervariable Region 3 Residues of HIV Type 1 gp120 Involved in CCR5 Coreceptor Utilization: Therapeutic and Prophylactic Implications," Proc Natl Acad Sci U S A 1999 Apr 13;96(8):4558-62.
Using alanine-scanning mutagenesis, Wang et al. searched for V3 residues critical for binding to the CCR5 coreceptor. They found several such residues: not only the previously described conserved residues, but also several that varied among HIV-1 subtypes.
"It is believed that HIV-1 may have evolved to rely on antigenic variation in this functionally important domain of gp120 to evade immune surveillance," Wang et al. wrote. "Our finding that CCR5 coreceptor utilization by HIV-1 involves not only conserved but also variable residues raises the possibility that antigenic variation in the coreceptor-binding domain of gp120 poses another challenge to HIV-1 vaccines targeting the entry steps of the HIV-1 life cycle."
This work was supported by grants from the National Institutes of Health.
The corresponding author for this study is Tun-Hou Lee, Department of Immunology and Infectious Diseases, Harvard School of Public Health, 651 Huntington Avenue, Boston, Massachusetts 02115. Email: <tunhoule@hsph.harvard.edu>.
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