The lectins griffithsin, cyanovirin-N and scytovirin inhibit HIV-1 binding to the DC-SIGN receptor and transfer to CD4(+) cells

Virology. 2012 Feb 20;423(2):175-86. doi: 10.1016/j.virol.2011.12.001. Epub 2011 Dec 29.

Abstract

It is generally believed that during the sexual transmission of HIV-1, the glycan-specific DC-SIGN receptor binds the virus and mediates its transfer to CD4(+) cells. The lectins griffithsin (GRFT), cyanovirin-N (CV-N) and scytovirin (SVN) inhibit HIV-1 infection by binding to mannose-rich glycans on gp120. We measured the ability of these lectins to inhibit both the HIV-1 binding to DC-SIGN and the DC-SIGN-mediated HIV-1 infection of CD4(+) cells. While GRFT, CV-N and SVN were moderately inhibitory to DC-SIGN binding, they potently inhibited DC-SIGN-transfer of HIV-1. The introduction of the 234 glycosylation site abolished HIV-1 sensitivity to lectin inhibition of binding to DC-SIGN and virus transfer to susceptible cells. However, the addition of the 295 glycosylation site increased the inhibition of transfer. Our data suggest that GRFT, CV-N and SVN can block two important stages of the sexual transmission of HIV-1, DC-SIGN binding and transfer, supporting their further development as microbicides.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Algal Proteins / pharmacology*
  • Bacterial Proteins / pharmacology*
  • CD4-Positive T-Lymphocytes / drug effects
  • CD4-Positive T-Lymphocytes / metabolism
  • CD4-Positive T-Lymphocytes / virology*
  • Carrier Proteins / pharmacology*
  • Cell Adhesion Molecules / antagonists & inhibitors
  • Cell Adhesion Molecules / genetics
  • Cell Adhesion Molecules / metabolism*
  • Cell Line
  • Down-Regulation / drug effects*
  • HIV Envelope Protein gp120 / genetics
  • HIV Envelope Protein gp120 / metabolism
  • HIV Infections / drug therapy
  • HIV Infections / genetics
  • HIV Infections / metabolism*
  • HIV Infections / virology
  • HIV-1 / drug effects
  • HIV-1 / genetics
  • HIV-1 / metabolism*
  • Humans
  • Lectins / pharmacology*
  • Lectins, C-Type / antagonists & inhibitors
  • Lectins, C-Type / genetics
  • Lectins, C-Type / metabolism*
  • Membrane Proteins
  • Plant Lectins
  • Protein Binding / drug effects
  • Receptors, Cell Surface / antagonists & inhibitors
  • Receptors, Cell Surface / genetics
  • Receptors, Cell Surface / metabolism*
  • Receptors, HIV / antagonists & inhibitors
  • Receptors, HIV / genetics
  • Receptors, HIV / metabolism

Substances

  • Algal Proteins
  • Bacterial Proteins
  • Carrier Proteins
  • Cell Adhesion Molecules
  • DC-specific ICAM-3 grabbing nonintegrin
  • HIV Envelope Protein gp120
  • Lectins
  • Lectins, C-Type
  • Membrane Proteins
  • Plant Lectins
  • Receptors, Cell Surface
  • Receptors, HIV
  • scytovirin protein, S varium
  • cyanovirin N
  • griffithsin protein, Griffithsia