Laboratory of Virus-Cell Interaction
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.
Despite decades of intense research, many features of HIV and other retroviruses remain obscure. Virus replication is regulated by the complex and not always well understood activity of multifunctional viral proteins to gain optimal advantage of the host machinery. On the other hand, as a result of its co-evolution with viral parasites, the host cell has developed mechanisms to interfere with the viral replication. We are exploring both aspects of this host-parasite relationship.
Retroviral factors which promote virus replication
Nef-like infectivity 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.
A novel activity of Nef-like proteins. The ability to mount a neutralizing immune response is key to control viral infections. In addition to their activity on virus infectivity, we have identified the ability of Nef and glycosylated Gag to increase retrovirus resistance to neutralizing antibodies targeting the membrane proximal external r