Preliminary studies on the use of pertussis toxin for the modulation of intravaginal SIV transmission in rhesus macaques

• Type of Material: Article
• Authors: Kristina Ortiz, Emory University; Rebecca S Sampathkumar, University of Nebraska Medical Center; Siddappa Byrareddy, Emory University; Aftab Ansari, Emory University
• Language: English
• Date: 2017-12-01
• Publisher: Wiley: 12 months
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
• Final Published Version (URL): http://dx.doi.org/10.1111/jmp.12316
• Title of Journal or Parent Work: Journal of Medical Primatology
• ISSN: 0047-2565
• Volume: 46
• Issue: 6
• Start Page: 327
• End Page: 331
• Grant/Funding Information: The studies were supported by NIH R01 AI 98628 to AAA, and NIH R01 AI113883 to SNB and the base grant to the Yerkes National Primate Research Center of Emory University NIH-ORIP-OD-51OD-11132 supported this study.
• Keywords: vaginal transmission; IMMUNODEFICIENCY VIRUS; G-protein-coupled receptors; Life Sciences & Biomedicine; SEX WORKERS; INFECTION; pertussis toxin; Science & Technology; PROTECTION; Zoology; HIV; SIVmac251; rhesus macaques; Veterinary Sciences
• Research Categories: Biology, Zoology; Health Sciences, Immunology

Abstract

Background: Pertussis toxin (PTX) blocks GPCR signaling resulting in the inhibition of chemotaxis/cell adhesion. It was reasoned that inhibition of cell trafficking may be an approach to prevent HIV/SIV transmission. Methods: In this study, PTX in HEC gel was applied to the vaginal wall of monkeys that were then challenged intravaginally with SIVmac251. Results: Results of these studies showed that 2 of 4 animals were resistant to infection. Furthermore, infection was correlated with a marked increase in the plasma and cervicovaginal lavage levels of select chemokines and cytokines. Conclusions: Results from this preliminary feasibility study dictate that further studies that include a larger number of animals are required to optimize this protocol and establish the efficacy of this approach. In addition, such future studies will provide important information on the role of specific chemokines that play a role in lymphocyte trafficking within the genital tract and serve as additional therapeutic targets.