Saturday, 23rd June 2018

Genome Dynamics and Function

          Viral proteins that modify gene expression







Luis Carrasco







Research summary:

Our research group is studying different viral proteins that are harmful for mammalian cells during viral replication. We are also analysing the mechanisms that regulate translation of cellular and viral mRNAs. We have focused our attention on two groups of cytopathogenic viral proteins: proteases and viroporins. In addition, we have devoted part of our research efforts to elucidate the presence of fungal infections as potential cause of several human diseases of unknown ethiology. Viral proteins. Recently, we have revised the different existing viroporins and their mode of action. These proteins are encoded by a variety of viruses and exhibit adverse effects on several cellular functions. The main activity of viroporins during the virus life cycle is to promote the exit of new virus particles from infected cells (Figure 1).

Our group has dedicated particular attention to the study of picornavirus and HIV proteases. We have examined the effect of these proteases on translation of several mRNAs and the correlation with the hydrolysis of different translation factors. Notably, we have found that picornavirus proteases 2A and L are able to confer independence for eIF2 during the translation of viral mRNAs.

Regulation of translation. We have described that some viral mRNAs are translated by a dual mechanism and require different initiation factors according to the context of their translation. Sindbis virus constitutes a good model system for these studies. Translation of the subgenomic mRNA from this virus does not utilize several initiation factors. Recently, we have described the eIF4A independence for the translation of this subgenomic mRNA in the infected cells, but this factor is necessary for translation in cell free systems. At present, we are carrying out different constructs that modify the structure of this subgenomic mRNA to determine with more precision its mechanism of translation.


 Fig01-300 ----

Viroporins promote the budding of new virus particles from cellular membranes.




    • Sánchez-Martínez, S., Madan, V., Carrasco, L. and Nieva, J.L. Membrane-active peptides derived from picornavirus 2B viroporin. Current Protein Pept. Sci. 13, 632-643 (2012).
    • Pisa, D., Alonso, R. and Carrasco, L. (2011) Fungal infection in a patient with multiple sclerosis. J. Clin. Microbiol. Infect. Dis.30, 1173-1180.
    • Castelló, A., Alvarez, E. and Carrasco, L. (2011) The multifaceted poliovirus 2A protease. Regulation of gene expression by picornavirus proteases. J. Biomed. Biotechnol. 2011:369648.
    • Welnowska, E., Sanz, M.A., Redondo, N. and Carrasco, L. (2011) Translation of viral mRNA without active eIF2: the case of picornaviruses. PLos One, 6(7), e22230
    • Alvarez, E., Castelló, A., Carrasco, L. and Izquierdo, J.M. (2011) Alternative splicing, a new target to block cellular gene expression by poliovirus 2A protease. Biochem. Biophys. Res. Commun. 414, 142-147.


Doctoral theses:

Natalia Redondo Sevillano (2012). Requerimiento de factores de iniciación para la traducción de mRNAs de picornavirus. Universidad Autónoma de Madrid. Luís Carrasco y Vanesa Madan y Miguel Ángel Sanz.

Ewelina Welnowska (2012).Independencia de factores de iniciación en la traducción de los mRNAs virales. Universidad Autónoma de Madrid. Luís Carrasco/Alfredo Castelló.