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Study of autophagy regulation and innate immunity in African Swine Fever Virus infection

AUTOR/es: Raquel Muñoz Moreno

DIRECTOR/es: Covadonga Alonso Martí


PALABRAS CLAVE: inmunidad innata, autofagia, ASFV, patogenia, Bcl2, Beclin1, agresoma

We have investigated the role of autophagy and the innate immune response of the host cell in African swine fever virus (AFSV) infection. These two processes have been recently linked together in the early defense mechanism of the cell against external pathogens, including viruses. Upon viral entry, ASFV inhibits autophagy persistently throughout the infectious cycle to facilitate replication and to avoid virus clearance. Further analysis revealed that ASFV-mediated autophagy inhibition depends on the specific interaction of ASFV Bcl2 homolog and apoptotic inhibitor A179L with the autophagy-related cell protein Beclin1. The ASFV-mediated autophagy inhibition is a tightly regulated process, since altering key autophagy factors impairs infectivity, the formation of the ASFV viral factories and the replication of the virus overall. Analysis of viral factory formation and distribution revealed that viral factories resemble aggresomes, but they are not consistent with aggresome formation mechanisms. In fact, inhibition of canonical BAG3 and HDAC6-mediated aggresome formation pathways did not alter the formation of ASFV viral factories. Finally, our studies established a link between autophagy, ASFV infection and innate immunity by the expression of the interferon-induced transmembrane (IFITM) protein family, which possesses antiviral properties against several viruses. These studies will allow better and more efficient antiviral intervention strategies against the disease.

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