期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 107, 期 31, 页码 13800-13805出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1006498107
关键词
HIV; 2G12; gp120; glycosylation; vaccine
资金
- International AIDS Vaccine Initiative
- Oxford Glycobiology Endowment
- National Institute of Allergy and Infectious Diseases [AI33292]
- Ragon Institute
The envelope spike of HIV is one of the most highly N-glycosylated structures found in nature. However, despite extensive research revealing essential functional roles in infection and immune evasion, the chemical structures of the glycans on the native viral envelope glycoprotein gp120-as opposed to recombinantly generated gp120-have not been described. Here, we report on the identity of the N-linked glycans from primary isolates of HIV-1 (clades A, B, and C) and from the simian immunodeficiency virus. MS analysis reveals a remarkably simple and highly conserved virus-specific glycan profile almost entirely devoid of medial Golgi-mediated processing. In stark contrast to recombinant gp120, which shows extensive exposure to cellular glycosylation enzymes (>70% complex type glycans), the native envelope shows barely detectable processing beyond the biosynthetic intermediate Man(5)GlcNAc(2) (<2% complex type glycans). This oligomannose (Man(5-9)GlcNAc(2)) profile is conserved across primary isolates and geographically divergent clades but is not reflected in the current generation of gp120 antigens used for vaccine trials. In the context of vaccine design, we also note that Man alpha 1 -> 2Man-terminating glycans (Man(6-9)GlcNAc(2)) of the type recognized by the broadly neutralizing anti-HIV antibody 2G12 are 3-fold more abundant on the native envelope than on the recombinant monomer and are also found on isolates not neutralized by 2G12. The Man alpha 1 -> 2Man residues of gp120 therefore provide a vaccine target that is physically larger and antigenically more conserved than the 2G12 epitope itself. This study revises and extends our understanding of the glycan shield of HIV with implications for AIDS vaccine design.
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