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ANKFY1 suppresses PDCoV replication by degrading viral nsp8 protein via p62-dependent selective autophagy
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DOI：10.1016/j.vetmic.2026.110927.png)
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Abstract
En 中文
Porcine deltacoronavirus (PDCoV) is an emerging enteric pathogen that causes severe gastrointestinal disease in neonatal piglets and poses a potential risk of cross-species transmission. Although viral strategies that counteract host immune responses have been widely studied, host factors that restrict PDCoV replication remain poorly characterized. In this study, we identify ANKFY1 as a previously unrecognized host factor that restricts PDCoV replication. PDCoV infection markedly upregulated ANKFY1 expression in LLC-PK1 cells. Using gain-and loss-of-function approaches, we demonstrated that ANKFY1 significantly suppresses PDCoV replication, whereas depletion of ANKFY1 restored both viral RNA synthesis and progeny virus production. Mechanistically, ANKFY1 specifically interacts with the viral nonstructural protein nsp8 and promoted its degradation. We further show that ANKFY1 recruits the E3 ubiquitin ligase Cullin 3 to catalyze K63/K33-linked ubiquitination of nsp8, primarily at lysine 58. The ubiquitinated nsp8 is subsequently recognized by the selective autophagy receptor p62 and delivered to autolysosomes for degradation. Disruption of p62 or autophagy flux abolished ANKFY1-mediated nsp8 degradation and antiviral activity, underscoring the essential role of the ANKFY1-Cullin3-p62 axis. Collectively, our results reveal a novel host defense mechanism in which ANKFY1 mediates selective autophagic degradation of PDCoV nsp8 to restrict viral replication. This study not only advances our understanding of PDCoV-host interactions but also identifies the ANKFY1-Cullin3-p62 pathway as a potential target for developing of broad-spectrum antiviral strategies.
Keywords:
ANKFY1
Nsp8 protein
PDCoV
P62
Cullin3
Selective autophagy
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2.7
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215
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1.7W
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