Evaluation of inflammatory and regulatory mechanisms in exposed newborns not infected by HIV-1

Abstract

Newborns exposed to HIV-1 but not infected (NB-ENI) show higher morbidity and mortality from infectious diseases. This prognosis is possibly related to immunoactivation caused by chronic maternal infection even in association with antiretroviral therapy (ART). In this project we will investigate the immunological mechanisms involved in the immunocompromise of RN-ENI. In order to explore possible alterations in the intrinsic response of different cell types, a single-cell RNA sequencing (scRNAseq) analysis will be performed in mononuclear cells from umbilical cord blood of newborns from mothers infected with HIV-1. The participation of the pathways of interest in the immunoactivation of RN-ENI will be confirmed by in vitro experiments. At the same time, our research group showed the participation of signaling mediated by ATP and adenosine nucleotides in the inflammatory immunopathogenesis of COVID-19 . However, the contribution of this pathway in the immunological imbalance of RN-ENI has not yet been explored. Thus, we will also evaluate the metabolism and purinergic signaling in samples of these NBs exposed to HIV-1. The findings of this study will contribute to the elucidation of inflammation/regulation mechanisms in the newborn of mothers affected by viral infections proposed by the Thematic Project, in addition to indicating potential targets for the development of therapeutic strategies. (AU)