Prevention of vaginal SHIV transmission in rhesus macaques through inhibition of CCR5.
Topical agents, such as microbicides, that can protect against human immunodeficiency virus (HIV) transmission are urgently needed. Using a chimeric simian/human immunodeficiency virus (SHIV SF162), which is tropic for the chemokine receptor CCR5, we report that topical application of high doses of PSC-RANTES, an amino terminus-modified analog of the chemokine RANTES, provided potent protection against vaginal challenge in rhesus macaques. These experimental findings have potentially important implications for understanding vaginal transmission of HIV and the design of strategies for its prevention.
Lederman
Michael M
MM
Department of Medicine, Case Western Reserve University, University Hospitals, 2061 Cornell Road, Cleveland, OH 44106, USA.
Veazey
Ronald S
RS
Offord
Robin
R
Mosier
Donald E
DE
Dufour
Jason
J
Mefford
Megan
M
Piatak
Michael
M
Lifson
Jeffrey D
JD
Salkowitz
Janelle R
JR
Rodriguez
Benigno
B
Blauvelt
Andrew
A
Hartley
Oliver
O
D000282:Administration, Intravaginal; D000818:Animals; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D000891:Anti-Infective Agents, Local / Q000008:administration & dosage / Q000627:therapeutic use*; D000914:Antibodies, Viral / Q000097:blood; D065100:CCR5 Receptor Antagonists; D018946:Chemokine CCL5 / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D005260:Female; D015658:HIV Infections / Q000517:prevention & control* / Q000635:transmission; D015497:HIV-1 / Q000187:drug effects; D008253:Macaca mulatta; D019713:Receptors, CCR5 / Q000378:metabolism; D016097:Simian Acquired Immunodeficiency Syndrome / Q000517:prevention & control* / Q000635:transmission; D015302:Simian Immunodeficiency Virus / Q000187:drug effects / Q000276:immunology; D014621:Vagina / Q000821:virology*
D019380:Anti-HIV Agents; D000891:Anti-Infective Agents, Local; D000914:Antibodies, Viral; D065100:CCR5 Receptor Antagonists; D018946:Chemokine CCL5; C492865:RANTES, N(alpha)-(n-nonanoyl)-desSer(1)-(thioproline(2),cyclohexylglycine(3))-; D019713:Receptors, CCR5