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Protection of neutralization epitopes in the V3 loop of oligomeric human immunodeficiency virus type I glycoprotein 120 by N-linked oligosaccharides in the V1 region

Författare

  • Britt Losman
  • Anders Bolmstedt
  • Kristian Schonning
  • Åsa Björndal
  • Charlotta Westin
  • Eva Maria Fenyö
  • Sigvard Olofsson

Summary, in English

The V3 region of the human immunodeficiency virus type 1 envelope protein gp120 constitutes a potential neutralization target, but the oligosaccharide of one conserved N-glycosylation site in this region protects it from neutralizing antibodies. Here, we determined whether N-linked glycans of other gp120 domains were also involved in protection of V3 neutralization epitopes. Two molecular clones of HIV-1, one lacking three N-Iinked glycans of the V1 region (HIV-1(3N/V1)) and another lacking three N-linked glycans of the C2 region (HIV-1(3N/C2)), were created and characterized. gp120 from both mutated viral clones had higher electrophoretic mobilities than gp120 from wild-type virus, confirming loss of N-linked glycans. Wild-type virus and both mutant clones replicated equally well in established T cell lines and all three viruses were able to utilize CXCR4 but not CCR5 as a coreceptor. The induced mutations increased gp120 affinity for CXCR4 but caused no corresponding increase in viral ability to replicate in T cell lines. HIV-1(3N/V1) was neutralized at about 25 times lower concentrations of an antibody to the V3 region than were wild-type virus and HIV-1(3N/C2). Soluble, monomeric gp120 from HIV-1(3N/V1) and wild type virus had identical avidity for the V3 antibody, indicating that the V1 glycans were able to shield V3 only in oligomeric but not monomeric gp120. In conclusion, one or more N-linked glycans of gp120 V1 is engaged in protection of the V3 region from potential neutralizing antibodies, and this effect is dependent on the oligomeric organization of gp120/gp4l.

Publiceringsår

2001

Språk

Engelska

Sidor

1067-1076

Publikation/Tidskrift/Serie

AIDS Research and Human Retroviruses

Volym

17

Issue

11

Dokumenttyp

Artikel i tidskrift

Förlag

Mary Ann Liebert, Inc.

Ämne

  • Microbiology in the medical area

Status

Published

ISBN/ISSN/Övrigt

  • ISSN: 1931-8405