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

J Med Primatol. 2017 Dec;46(6):327-331. doi: 10.1111/jmp.12316. Epub 2017 Sep 21.

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.

Keywords: G-protein-coupled receptors; SIVmac251; pertussis toxin; rhesus macaques; vaginal transmission.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Female
  • HIV / drug effects
  • HIV / physiology
  • HIV Infections / prevention & control
  • HIV Infections / virology
  • Macaca mulatta*
  • Monkey Diseases / prevention & control*
  • Monkey Diseases / virology
  • Pertussis Toxin / pharmacology*
  • Simian Acquired Immunodeficiency Syndrome / prevention & control*
  • Simian Acquired Immunodeficiency Syndrome / virology
  • Simian Immunodeficiency Virus / drug effects*
  • Simian Immunodeficiency Virus / physiology
  • Vagina / virology*

Substances

  • Pertussis Toxin