Saturday, 16th December 2017

Virología y microbiología

         African swine fever virus





María L. Salas Falgueras




Research summary:

The African swine fever virus (ASFV) protease that processes the viral polyproteins is required for a late maturational step in virus core assembly and production of infectious progeny virus. On the other hand, studies on ASFV morphogenesis have shown a correlation between proteolytic processing of polyproteins and correct virus assembly, suggesting that the activity of the protease might be modulated during the infection. Indeed, recent studies demonstrated that the protease activity is controlled by two disulfide bridges formed between cysteines C14 and C24 and between C45 and C50. To investigate the mechanism of this redox regulation, we have studied the interaction of the wild type protease and punctual mutants of the involved cysteines to serine with the substrate polyprotein pp62. Our results show, in pull down experiments, the binding of the wild type but not the mutated protease to polyprotein pp62, indicating that the intramolecular disulfide bonds are necessary for the interaction of the protease with its substrate.

          nnnnn     Fig1 300px
  Cells infected with the recombinant virus inducible in the PK. A. Viral factory. B. Viral particles at the plasmatic membrane for exit from the cell..

The function of ASFV genes in virus replication is being studied by the generation of virus recombinants where de gene under study is placed under the control of an IPTG inducible promoter. We have constructed a virus recombinant inducible in gene R298L coding for a viral protein kinase (PK), showing that the PK is not expressed under repression conditions in the absence of IPTG. Under these conditions, infectious intracellular and extracellular virus is produced and the viral particles are morphologically indistinguishable from those produced in an infection with the parental virus. These results indicate that the viral PK is dispensable for the replication of the virus in cells in culture.


Selected Publications:

  • Salas, M. L. and Andrés, G. (2013) African swine fever virus morphogenesis, Virus Res.173, 29-41.
  • Rodríguez, J. M. and Salas, M. L. (2013) African swine fever virus transcription. Virus Res. 173, 15-28.
  • Redrejo-Rodríguez, M., Rodríguez, J. M., Suárez, C., Salas, J. and Salas, M. L. (2013) Involvement of the reparative DNA polymerase pol X of African swine fever virus in the maintenance of viral genome stability. J. Virol. 87, 9780-9787.
  • Redrejo-Rodríguez, M. and Salas, M. L. (2014) Repair of base damage and genome maintenance in the Nucleo-Cytoplasmic Large DNA Viruses. Virus Res. 179, 12-25.
  • Lacasta, A., Ballester, M., Moteagudo, P. L., Rodríguez, J. M., Salas, M. L., Accensi, F., Pina-Pedrero, S., Bensaid, A., Argilaguet, J., López-Soria, S., Hutet, E., Lepotier, M. F. and Rodríguez, F. (2014) Expression library immunization can confer protection against lethal challenge with African swine fever virus. J. Virol. 88, 13322-13332.