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.
Department of Medicine, Case Western Reserve University, University Hospitals, 2061 Cornell Road, Cleveland, OH 44106, USA.
Michael M
MM
Lederman
Ronald S
RS
Veazey
Robin
R
Offord
Donald E
DE
Mosier
Jason
J
Dufour
Megan
M
Mefford
Michael
M
Piatak
Jeffrey D
JD
Lifson
Janelle R
JR
Salkowitz
Benigno
B
Rodriguez
Andrew
A
Blauvelt
Oliver
O
Hartley
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