On virus tropism, reservoirs, pathogenic and protective immune responses; what can we learn from HIV-2?

In the proposed project we will study HIV-2 as a model of a relatively benign and well-controlled HIV infection and aim to provide basic knowledge on the distinct pathogenesis of HIV-1 and HIV-2.

We expect that the results in the future may guide in the design of therapeutic, possibly curative, and prophylactic strategies against both HIV-1 and HIV-2.

The proposal is based on 1) an internationally unique cohort including mono and dually HIV-1 and HIV-2 infected individuals; 2) innovative in vitro infection models; 3) state-of-the-art molecular and bioinformatic tools and 4) strong collaborative network.

Given that HIV-2 is such an understudied virus, above components will assure scientific novelty.We will study virus-host interactions in HIV-1 and HIV-2 infections, divided according to viral control (viremic, low/aviremic and extreme elite controllers).

Specifically we aim to study:Virus tropism, including fine specificity of virus host cell tropism, and lectin use for modulation of infectionVirus reservoirs, including phenotypic characterization of CD4+ T cells holding intact and inducible viral genomes, integration sites and epigenetic regulationProtective immune responses, including intra- and intertype cross-reactive immunity, e.g. antibodies, CD4+ and CD8+ T cellsPathogenic immune responses, including analyses of immune dysregulation and immune-mediated tissue damageViral molecular traits that translate into phenotypic features studied under above points