Resistance of human immunodeficiency virus type 1 to the high-mannose binding agents cyanovirin N and concanavalin A

J Virol. 2005 Jun;79(12):7777-84. doi: 10.1128/JVI.79.12.7777-7784.2005.


Due to the biological significance of the carbohydrate component of the human immunodeficiency virus type 1 (HIV-1) glycoproteins in viral pathogenesis, the glycosylation step constitutes an attractive target for anti-HIV therapy. Cyanovirin N (CV-N), which specifically targets the high-mannose (HM) glycans on gp120, has been identified as a potent HIV-1 entry inhibitor. Concanavalin A (ConA) represents another mannose-binding lectin, although it has a lower specificity for HM glycans than that of CV-N. For the present study, we selected CV-N- and ConA-resistant HIV-1 strains in the presence of CV-N and ConA, respectively. Both resistant strains exhibited a variety of mutations eliminating N-linked glycans within gp120. Strains resistant to CV-N or ConA displayed high levels of cross-resistance towards one another. The N-glycan at position 302 was eliminated in both of the lectin-resistant strains. However, the elimination of this glycan alone by site-directed mutagenesis was not sufficient to render HIV-1 resistant to CV-N or ConA, suggesting that HIV-1 needs to mutate several N-glycans to become resistant to these lectins. Both strains also demonstrated clear cross-resistance towards the carbohydrate-dependent monoclonal antibody 2G12. In contrast, the selected strains did not show a reduced susceptibility towards the nonlectin entry inhibitors AMD3100 and enfuvirtide or towards reverse transcriptase or protease inhibitors. Recombination of the mutated gp160 genes of the strains resistant to CV-N or ConA into a wild-type background fully reproduced the (cross-)resistance profiles of the originally selected strains, pointing to the impact of the N-glycan mutations on the phenotypic resistance profiles of both selected strains.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-HIV Agents / pharmacology*
  • Antibodies, Monoclonal / immunology
  • Antibodies, Monoclonal / metabolism
  • Bacterial Proteins / metabolism*
  • Bacterial Proteins / pharmacology*
  • Carrier Proteins / metabolism*
  • Carrier Proteins / pharmacology*
  • Cell Line
  • Concanavalin A / metabolism
  • Concanavalin A / pharmacology*
  • Drug Resistance, Viral*
  • Glycosylation
  • HIV Envelope Protein gp120 / chemistry
  • HIV Envelope Protein gp120 / genetics
  • HIV Envelope Protein gp120 / metabolism
  • HIV Envelope Protein gp160 / chemistry
  • HIV Envelope Protein gp160 / genetics
  • HIV Envelope Protein gp160 / metabolism
  • HIV-1 / drug effects*
  • HIV-1 / genetics
  • Humans
  • Mannose / metabolism*
  • Microbial Sensitivity Tests
  • Models, Molecular
  • Mutation


  • Anti-HIV Agents
  • Antibodies, Monoclonal
  • Bacterial Proteins
  • Carrier Proteins
  • HIV Envelope Protein gp120
  • HIV Envelope Protein gp160
  • Concanavalin A
  • cyanovirin N
  • Mannose