Cells and viruses
The survival and replication of viruses depends on their ability to control, hijack, and profit from the activity of the host cell. Deciphering the interaction between the virus and the host cell throughout its life cycle is instrumental not only for the identification of novel potential opportunities for antiviral intervention but also for a deeper mechanistic knowledge of the cellular machinery. We are interested in both aspects: exploring the way viruses interact with host cellular components and improving our understanding of the host pathways involved.
The Nef protein of HIV and similar retroviral factors
Nef is a multifunctional regulatory protein expressed by primate lentiviruses, crucial for HIV replication and progression to AIDS. Among its activities, Nef potentiates the infectivity of HIV using a mechanism which still remains unexplained. While this was thought to be an exclusive prerogative of primate lentiviruses, we have discovered that a regulatory protein (glycosylated gag) expressed by gammaretroviruses has a similar activity on the infectivity of the retrovirus particle, providing a compelling example of convergent evolution within two divergent groups of retroviruses. We are exploring the molecular mechanisms triggered by these factors and investigating the presence of yet undetected Nef-like virus infectivity factors in other virus groups.
The innate immunity system provides the first response following the encounter of the host with a pathogen. Several restriction factors capable of counteracting and sensing viral pathogens have been revealed in the last 15 years. A fundamental addition to this list is the SERINC family of proteins, which we have recently discovered to inhibit diverse retroviruses. In humans this family includes five members, of which SERINC5 and SERINC3 were found to inhibit HIV-1. Human SERINC5, in particular, displays a potent activity targeting the infectivity of retroviral particles with a mechanism which yet remains unknown. SERINC5 is a multipass transmembrane protein localized almost exclusively on the plasma membrane and enriched in virus particles. Retroviruses have developed factors such as Nef and glycoGag capable of antagonizing SERINC by promoting its relocalization into the late endosomal compartment and hence preventing its incorporation into virions.