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Pathogenesis & Transmission

HIV Mother to child transmission

This study will address the obstacles identified in the PROMISE-PEP/ANRS 12174 trial to reduce further postnatal HIV-1 transmission. Understanding the determinants of HIV viral production in breast milk is one objective, improving a sustained drug adherence for infant prophylaxis another one. We also propose to assess the risks of such infant prophylaxis intervention PROMISE M&S; PROMISE EPI.

Neurovirology

Molecular and Cellular Mechanisms of Nervous System Infections. We are interested in the molecular and cellular mechanisms of viral infections of the central nervous system (CNS). In particular, we study the effects of chronic infections (human immunodeficiency virus and acute viruses (emerging arboviruses, such as Zika and Usutu viruses) on different types of neural cells (neurons, neuroprecursors, astrocytes, microglia, pericytes). We also study the mechanisms of entry into the CNS of these viruses by focusing on the blood-brain barrier and axonal transport using ex vivo and in vivo approaches coupled with molecular and cellular biology techniques, biochemistry and imaging (confocal microscopy, electron microscopy, etc…). The aim of these projects is to identify the trafficking and signaling pathways involved during these infections as well as the cellular response (anti-viral, apoptotic, pyroptotic…) and the long-term effect on neuronal homeostasis.

 

Endogenous Retroviruses & human auto-inflammatory diseases

Ancient viral infections have left their marks in mamalian genoma through out the evolution. Indeed endogenous retroviruses encompass about 8% of human genome. Their relationship with human auto-inflammatory diseases is a long-lasting history and several pathogenic mechanisms have been suggested. We recently developed a new concept to explain the induction of auto-inflammation. It relies on the production of RNA:Dna duplexes by endogenous reverse transcriptases. In the next years, we will decipher the molecular mechanisms underlying the induction of auto-inflammation and evaluate the use of reverse transcriptase inhibitors in such diseases. The focus will be done on a frequent skin disease, namely the psoriasis.

Nicolas Nagot

Scientific supervisor

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