Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2000 Aug;74(15):6769-76.
doi: 10.1128/jvi.74.15.6769-6776.2000.

V2 loop glycosylation of the human immunodeficiency virus type 1 SF162 envelope facilitates interaction of this protein with CD4 and CCR5 receptors and protects the virus from neutralization by anti-V3 loop and anti-CD4 binding site antibodies

A Ly  1 , L Stamatatos
Affiliations

V2 loop glycosylation of the human immunodeficiency virus type 1 SF162 envelope facilitates interaction of this protein with CD4 and CCR5 receptors and protects the virus from neutralization by anti-V3 loop and anti-CD4 binding site antibodies

A Ly et al. J Virol. 2000 Aug.

Abstract

We examined the role of asparagine-linked glycosylation of the V2 loop of the human immunodeficiency virus (HIV) SF162 envelope on viral replication potential and neutralization susceptibility. We report that the asparagines located at the amino- and carboxy-terminal sites (at positions 154 and 195, respectively), as well as within the V2 loop of the SF162 envelope (at position 186), are glycosylated during in vitro replication of this virus in human peripheral blood mononuclear cells. Our studies indicate that glycosylation of the V2 loop, in particular at its base, facilitates the interaction of the HIV envelope with the CD4 and CCR5 receptor molecules present on the surface of target cells and affects viral replication kinetics in a cell type-dependent manner. In cells expressing high numbers of receptor molecules on their surfaces, the SF162-derived V2 loop-deglycosylated mutant viruses replicate as efficiently as the parental SF162 virus, while in cells expressing small numbers of receptor molecules, the mutant viruses replicate with markedly reduced efficiency. In addition to expanding the viral tropism, V2 loop glycosylation at the three sites examined prevents neutralization by anti-CD4 binding site antibodies. In contrast, glycosylation at the amino- and carboxy-terminal sites of the V2 loop but not within the loop itself offers protection against anti-V3 loop antibodies. Thus, the epitopes masked by the sugar molecules present on the three glycosylation sites examined are not identical but overlap.

PubMed Disclaimer

Figures

FIG. 1
FIG. 1
Amino acid sequence of the V2 loop of the SF162 envelope. The amino acid sequence of the second hypervariable region of the SF162 envelope from isoleucine 152 to isoleucine 199 is shown. Underlined are the positions of potential N-linked glycosylation sites. The numbers indicate the location of asparagines (N) at positions 154, 186, and 195 of the SF162 envelope.
FIG. 2
FIG. 2
Electrophoretic mobility of virion-associated gp120 molecules during SDS-PAGE. The preparation of virion-associated gp120 molecules from the parental SF162 and the three glycosylation mutant viruses and SDS-PAGE were performed as described in Materials and Methods. No attempt was made to correct for differences in the gp120 content of the samples.
FIG. 3
FIG. 3
Replication in activated human PBMC (A) and primary human macrophages (B). The replication of the mutant viruses was compared to that of the parental SF162 isolate, as described in Materials and Methods. Values indicate the mean p24 concentration from triplicate wells, and the bars indicate the standard deviation from the mean (in the case of PBMC, the standard deviation has been omitted for clarity). One out of three independent experiments is shown.
FIG. 4
FIG. 4
Relative ratio of gp120 to p24 molecules in parental and mutant virions. The quantitation of gp120 and p24 proteins present in intact virions produced in PBMC was performed with the use of ELISA methodologies as described in Materials and Methods. The mean gp120-to-p24 ratio and the standard deviation from the mean from three independent experiments is shown.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Back N K T, Smit L, De Jong J-J, Keulen W, Schutten M, Goudsmit J, Tersmette M. An N-glycan within the human immunodeficiency virus type 1 gp120 V3 loop affects virus neutralization. Virology. 1994;199:431–438. - PubMed
    1. Bernstein H B, Tucker S P, Hunter E, Schutzbach J S, Compans R W. Human immunodeficiency virus type 1 envelope glycoprotein is modified by O-linked oligosaccharides. J Virol. 1994;68:463–468. - PMC - PubMed
    1. Botarelli P, Houlden B A, Haigwood N L, Servis C, Montagna D, Abrignani S. N-glycosylation of HIV-gp120 may constrain recognition by T lymphocytes. J Immunol. 1991;147:3128–3132. - PubMed
    1. Burns D P, Collignon C, Desrosiers R C. Simian immunodeficiency virus mutants resistant to serum neutralization arise during persistent infection of rhesus monkeys. J Virol. 1993;67:4104–4113. - PMC - PubMed
    1. Cheng-Mayer C, Brown A, Harouse J, Luciw P A, Mayer A J. Selection for neutralization resistance of the simian/human immunodeficiency virus SHIVSF33A variant in vivo by virtue of sequence changes in the extracellular envelope glycoprotein that modify N-linked glycosylation. J Virol. 1999;73:5294–5300. - PMC - PubMed

Publication types

MeSH terms