Encephalomyocarditis virus non-structural protein 2C degrades NDP52 autophagy protein to promote its own survival

Encephalomyocarditis virus (EMCV) is an important zoonotic pathogen that causes encephalitis and myocarditis, primarily in pigs and in some mammals. Nuclear dot protein (NDP) 52 is an important autophagy adaptor protein that is known to target microbial pathogens, including viruses into autophagosomes to facilitate the selective autophagy process. Here, we wanted to investigate how an important zoonotic virus such as EMCV interacts with NDP52. We found that NDP52 negatively regulates the entry and replication phases of EMCV and interacts with EMCV VP1/VP2 proteins to mediate its autophagic degradation. EMCV counteracts this by exerting autophagy induction through its encoded 2C protein. The autophagy machinery then hijacks NDP52 and transports it to lysosomes for subsequent degradation via late endosomal molecules Rab7 and Rab9. Our study describes a novel mechanism by which EMCV escapes the host's antiviral response to promote its survival by hijacking the autophagy pathway using the non-structural protein 2C of EMCV.