Project: Mucosal type I IFN desensitization and the risk of HIV acquisition

Acronym	MIDAS (Reference Number: TMA2016CDF-1582)
Duration	01/07/2018 - 30/06/2021
Project Topic	Host interferon (IFN) antiviral response is an important determinant of HIV transmission during sexual exposure. Recent data from animal models suggest that mucosal application of type I IFNs can block viral infection and might represent an HIV prevention strategy. However, in a large prospective cohort analysis of the CAPRISA 004 trial increased mucosal type I IFN expression was associated with increased risk of HIV acquisition. One of the explanations for this disceptency could be the timing and duration of IFN exposure. In the animal model, exogenous IFN exposure was brief, whereas in the humans, endogenous IFN expression can be maintained at high levels for prolonged period of time. This study will attempt to disentangle the mechanisms that govern positive and negative effects of IFN on HIV susceptibility. We will test the hypothesis that chronic type I IFN expression in the female reproductive tract causes dysregulation of IFN responsiveness, therefore increasing the susceptibility of HIV target cells in the mucosa. Specifically, patterns of type I IFN expression will be measured longitudinally at the female reproductive tract. Type I IFN levels will be plotted over time and cumulative IFN score will be calculated. We will identify participants with persistently high and low type I IFN levels. Type I IFN levels will then be correlated to demographic, clinical, behavioural and reproductive variables. Finally we will correlate the high/low IFN status with IFN responsiveness and altered HIV susceptibility of mucosal target cells. This study will contribute toward an understanding of how basic immunological mechanisms are exploited by HIV. Resolving the controversy around IFNs and HIV transmission is critical if IFN therapies are going to be considered for clinical translation. The proposed study will be conducted at the Centre for the AIDS Programme of Research in South Africa (CAPRISA), one of the South Africa’s best known research oganisations. This environment will provide the main applicant (Dr. Aida Sivro), with the necessary support and international research environment to further her development as an independent researcher. Furthermore, through this fellowship the main applicant will supervise students from University of KwaZulu- Natal, transferring her skills and knowledge to a new generation of young researchers from South Africa.
Network	EDCTP2
Call	Career Development Fellowships 2016

Project partner

Number	Name	Role	Country
1	Centre for the Aids Programme of Research in South Africa	Coordinator	South Africa