The lectins griffithsin, cyanovirin-N and scytovirin inhibit HIV-1 binding to the DC-SIGN receptor and transfer to CD4(+) cells.
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.
National Institute for Communicable Diseases, Johannesburg, South Africa.
Kabamba B
KB
Alexandre
Elin S
ES
Gray
Hazel
H
Mufhandu
James B
JB
McMahon
Ereck
E
Chakauya
Barry R
BR
O'Keefe
Rachel
R
Chikwamba
Lynn
L
Morris
D020418:Algal Proteins / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000494:pharmacology*; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000378:metabolism / Q000821:virology*; D002352:Carrier Proteins / Q000494:pharmacology*; D015815:Cell Adhesion Molecules / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D015536:Down-Regulation / Q000187:drug effects*; D015699:HIV Envelope Protein gp120 / Q000235:genetics / Q000378:metabolism; D015658:HIV Infections / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism* / Q000821:virology; D015497:HIV-1 / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D037102:Lectins / Q000494:pharmacology*; D037181:Lectins, C-Type / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D008565:Membrane Proteins; D037121:Plant Lectins; D011485:Protein Binding / Q000187:drug effects; D011956:Receptors, Cell Surface / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D015728:Receptors, HIV / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
D020418:Algal Proteins; D001426:Bacterial Proteins; D002352:Carrier Proteins; D015815:Cell Adhesion Molecules; D015699:HIV Envelope Protein gp120; D037102:Lectins; D037181:Lectins, C-Type; D008565:Membrane Proteins; D037121:Plant Lectins; D011956:Receptors, Cell Surface; D015728:Receptors, HIV; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin; C474342:scytovirin protein, S varium; C107733:cyanovirin N; C499654:griffithsin protein, Griffithsia