Role of Integrins in HIV/SIV Transmission Across the Cervico-Vaginal Mucosa
Council researchers are studying the earliest stages of vaginal HIV infection in rhesus macaques.
HIV is most commonly acquired by the mucosal route during sexual intercourse. Therefore, blocking this means of transmission will rapidly decrease HIV incidence.
In the days following mucosal exposure, HIV must overcome numerous barriers, which offers a window of opportunity to act before HIV establishes infection. Unfortunately, the critical events that take place after viral exposure are poorly understood.
Council research is exploring the host and viral determinants that facilitate virus replication and systemic infection and the early events after mucosal transmission in the female genital tract of rhesus macaques. In addition, because HSV-2 infection increases the risk of HIV acquisition, this research is exploring how HSV-2 influences these early events by using a model of HSV-2 vaginal infection recently established by the Council.
HIV binds to integrin α4β7, a molecule expressed on the surface of immune cells, which is critical for cell homing to the gut. Once HIV arrives in the gut, it can replicate at a very high rate. Recent findings suggest that the ability of HIV to interact with α4β7 may be one of the viral features that helps HIV survive the mucosal barrier. Because Council research has found that HSV-2 infection can modulate the α4β7 molecule, this project is studying how the modulation of α4β7 influences the early events after HIV mucosal transmission through the use of ex vivo and in vivo models. The ex vivo experiments explore the effect of HSV-2 infection on macaque tissues cultured in the laboratory that complement the in vivo studies in animals.
For the in vivo studies we are using a macaque model of HSV-2 infection in combination with a model of vaginal immunodeficiency virus transmission in macaques (SHIV). This combination constitutes a powerful new tool to study the earliest stages of vaginal HIV infection in a controlled manner, explore the effect of HSV-2, and determine how this influences susceptibility to vaginal HIV infection.
Moreover, to specifically investigate the role of the HIV receptor α4β7 we are testing how blocking or increasing the HIV binding to α4β7 influences susceptibility to mucosal transmission.
The frequency of [alpha]4[beta]7 high memory CD4 T cells correlates with susceptibility to rectal SIV infection (abstract) (HTML)
Martinelli,Elena; Veglia,Filippo; Goode,Diana J.; Guerra-Perez,Natalia; Aravantinou,Meropi; Arthos,James; Piatak Jr.,Michael; Lifson,Jeffrey D.; Blanchard,James; Gettie,Agegnehu; Robbiani,Melissa
Journal of Acquired Immune Deficiency Syndromes 64(4): 325-331
Publication date: 2013
Location: United States
HIV and AIDS
HIV biomedical research
Duration: 3/2012 - 3/2017
Population Council researchers:
Agegnehu Gettie (Aaron Diamond AIDS Research Center)
Andrei Konradi (Elan Pharmaceuticals)
James Arthos (US National Institutes of Health)
James Blanchard (Tulane National Primate Research Center)
Jeffrey Lifson (National Cancer Institute)
Michael Piatak (National Cancer Institute)
US National Institutes of Health