Cyanovirin-N inhibits AIDS virus infections in vaginal transmission models.
The cyanobacterial protein cyanovirin-N (CV-N) potently inactivates diverse strains of HIV-1 and other lentiviruses due to irreversible binding of CV-N to the viral envelope glycoprotein gp120. In this study, we show that recombinant CV-N effectively blocks HIV-1(Ba-L) infection of human ectocervical explants. Furthermore, we demonstrate the in vivo efficacy of CV-N gel in a vaginal challenge model by exposing CV-N-treated female macaques (Macaca fascicularis) to a pathogenic chimeric SIV/HIV-1 virus, SHIV89.6P. All of the placebo-treated and untreated control macaques (8 of 8) became infected. In contrast, 15 of 18 CV-N-treated macaques showed no evidence of SHIV infection. Further, CV-N produced no cytotoxic or clinical adverse effects in either the in vitro or in vivo model systems. Together these studies suggest that CV-N is a good candidate for testing in humans as an anti-HIV topical microbicide.
Tsai
Che-Chung
CC
Washington National Primate Research Center, University of Washington, Seattle, Washington 98105, USA. cctsai@bart.rprc.washington.edu
Emau
Peter
P
Jiang
Yonghou
Y
Agy
Michael B
MB
Shattock
Robin J
RJ
Schmidt
Ann
A
Morton
William R
WR
Gustafson
Kirk R
KR
Boyd
Michael R
MR
D000282:Administration, Intravaginal; D000818:Animals; D019380:Anti-HIV Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D001426:Bacterial Proteins; D002352:Carrier Proteins / Q000008:administration & dosage* / Q000627:therapeutic use; D002584:Cervix Uteri / Q000821:virology; D046508:Culture Techniques; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D015497:HIV-1 / Q000187:drug effects / Q000235:genetics / Q000472:pathogenicity; D006801:Humans; D008252:Macaca fascicularis; D016097:Simian Acquired Immunodeficiency Syndrome / Q000188:drug therapy* / Q000821:virology; D015302:Simian Immunodeficiency Virus / Q000187:drug effects / Q000235:genetics / Q000472:pathogenicity; D014621:Vagina / Q000821:virology*
D019380:Anti-HIV Agents; D001426:Bacterial Proteins; D002352:Carrier Proteins; C107733:cyanovirin N