Current research progress on the viral immune evasion mechanisms of African swine fever virus

African swine fever(ASF),caused by the ASF virus(ASFV),is an acute,severe,and highly contagious infectious disease in domestic pigs and wild boars.Domestic pigs infected with a virulent ASFV strain can have morbidity and mortality rates of up to 100%.The epidemic of ASF has caused serious economic losses to the global pig industry.Currently,there is no safe and efective vaccine or specifc drug for treating ASF.Therefore,ASFV still poses a great threat to pig factories.ASFV is a double-stranded DNA virus with a complex icosahedral multilayer structure.The ASFV genome contains 150-170 open reading frames(ORFs)that encode 150-200 proteins.Some ASFV-encoded proteins are involved in virus invasion,genome replication,DNA repair,and virion formation.Some ASFV proteins execute immunomodulatory functions by regulating the host antiviral innate immune response.Accumulating studies have shown that the immunomodulatory functions of ASFV genes are closely related to the virulence and pathogenicity of ASFV isolates.This review summarizes the research advances on ASFV immune evasion mechanisms in African swine fever patients and provides new insights for developing attenuated live vaccine candidates to prevent and control ASF.

Joint deletion of multifunctional MGF505-7R and H240R genes generates a safe and effective African swine fever virus attenuated live vaccine candidate

African swine fever(ASF)caused by the ASF virus(ASFV)is a highly contagious disease of pigs and wild boars.Currently,there are no safe,effective commercial vaccines available.The genome of ASFV HLJ/18 contains more than 180 genes,including a few virulence-related genes.Identifying these key virulence genes through individual deletion and subsequent pathogenicity testing in pigs is a laborious process.In addition,some ASFV genes are indispensable for viral replication and cannot be deleted.Over the past 30 years,scientists have confirmed that certain ASFV genes particularly those host antiviral innate immune responses,are associated with the virulence of ASFV strains.Although knockout of these genes does not impact viral replication,it does attenuate the virulence of ASFV in pigs.Pigs immunized with these live attenuated vaccine candidates can provide partial or complete protection.Based on these findings,we propose a new concept that ASFV immunomodulatory genes involved in type I interferon(IFN)production,IFN-JAK-STAT signaling,inflammatory responses,cell death(involved in apoptosis,necrosis,and pyroptosis),and autophagy may be related to the pathogenicity of ASFV.An unbiased screening may identify more ASFV immunomodulatory or multifunctional genes,simplifying the confirmation of ASFV virulence-related genes.In line with these theories,we have identified MGF505-7R and H240R as key virulence genes determining the pathogenicity of the ASFV HLJ/18 strain.Deletion of MGF505-7R,H240R alone or both attenuate the virulence of ASFV HLJ/18 in pigs,providing a paradigm for developing attenuated live vaccines from basic research results.