Analyses of inter- and intra-patient variation in the V3 loop of the HIV-1 envelope protein
- Los Alamos National Lab., NM (United States)
- Northwestern Univ., Chicago, IL (United States). Medical School
The third hypervariable domain of the HIV-1 gp120 envelope protein (V3) has been the focus of intensive sequencing efforts. To date, nearly one thousand V3 loop sequences have been stored in the HIV sequence database. Studies have revealed that the V3 loop elicits potent type-specific immune responses, and that it plays a significant role in cell tropism and fusion . The immunogenic tip of the loop can serve as a type-specific neutralizing antibody epitope, as well as a cytotoxic T-cell epitope. A helper T-cell epitope that lies within the amino terminal half of the V3 loop has also been characterized. Despite the richness of the immunologic response to this region, its potential for variation makes it an elusive target for vaccine design. Analyses of sibling sequence sets (sets of viral sequences derived from one person) show that multiple forms of the immunogenic tip of the loop are found within most HIV-1 infected individuals. Viral V3 sequences obtained from epidemiologically unlinked individuals from North America and Europe show extensive variation. However, some amino acid positions distributed throughout the V3 loop are highly conserved, and there is also conservation of the charge class of amino acid able to occupy certain positions relative to the tip of the loop. By contrast, the sequences obtained from many countries throughout the African continent reveal that V3 is a remarkably fluid region with few absolute constraints on the nature of the amino acids that can occupy most positions in the loop. The high degree of heterogeneity in this region is particularly striking in view of its contribution to biologically important viral functions.
- Research Organization:
- Los Alamos National Laboratory (LANL), Los Alamos, NM (United States)
- Sponsoring Organization:
- Department of Health and Human Services, Washington, DC (United States)
- DOE Contract Number:
- W-7405-ENG-36
- OSTI ID:
- 10104898
- Report Number(s):
- LA-UR-91-3716; CONF-9109315-1; ON: DE92003781
- Resource Relation:
- Conference: Vaccines `92,Cold Spring Harbor, NY (United States),19-23 Sep 1991; Other Information: PBD: 17 Sep 1991
- Country of Publication:
- United States
- Language:
- English
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