IrsiCaixa

Our main area of interest is the study of the interaction between the HIV virus and its target cells. In the process of this interaction, the protein of the cell envelope (its exterior protein) plays a key role, namely that it has a determining influence on the viral cytopathicicity (virulence) of the virus and in the response of antibodies effective against the virus.

In order to study these factors, our research group is conducting research into a strong cellular component closely linked with immunology and virology. Understanding how the HIV virus interacts with its target cells and how these cells respond to attack is crucial so as to determine the key points in the HIV life cycle which could be used as therapeutic targets, both pharmacological (antiretrovirals) and immunological (vaccines).

The HIV envelope protein is responsible for the union of the virus with the cell, and opening the cell membrane, a process known as “fusion”, enabling the entry of the virus and the subsequent infection of the target cell. As well as appearing on the surface of the virus, this protein is visible in the membrane of infected cells, and it is here that its functions are magnified, becoming the main cause of the destruction of CD4 cells and the spread of the viral infection.

Viruses joined to a CD4 cell
Viral synapse between an infected cell (left) and CD4 cell (right) (images courtesy of Maria Teresa Fernández Figueras, Dept of Pathological Anatomy, HUGTIP, Hospital Germans Trias I Pujol, Badalona.)

The appearance of the viral envelope over the surface of the cell enables it to establish strong contacts with surrounding target cells. These contacts, which form a synaptic structure called “viral synapse”, have been analyzed in the last few years in our laboratory using an excellent experimental model for studying HIV-induced cell death.

Our interest in cellular contact has been strengthened as a result of its role in the dissemination of in vivo viral infection via a mechanism known as “cell-to-cell viral transmission”. The study of this mechanism, the factors that control it and their consequences for in vivo viral infection (reservoirs, neutralizing antibodies and cell death) are all covered in the principal areas of investigation of the research group.
In order to address these issues, we need to identify both the different factors that affect the functions of the viral envelope, and the protein in the HIV virus with the most variability.  For this purpose, the group has developed techniques for analyzing RNA envelopes, their expansion over the surface of cells and the viruses themselves, their capacity to interact and fuse with target cells and escape mechanisms in drugs and antibodies.