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African swine fever virus MGF360-9L promotes viral replication by degrading the host protein HAX1.

Virus Research 2023 August 27
African swine fever virus (ASFV) infection causes African swine fever (ASF), a virulent infectious disease that threatens the safety of livestock worldwide. Studies have shown that MGF360-9L is important for the virulence of ASFV and the host protein HS1-associated protein X-1 (HAX1) plays an important role in viral pathogenesis. This study aimed to clarify the mechanism by which HAX1 mediates ASFV replication through interactions with MGF360-9L. The regions of interaction between MGF360-9L and HAX1 were predicted and validated. HAX1 overexpression and RNA interference studies revealed that HAX1 is a host restriction factor that suppresses ASFV replication. Moreover, HAX1 expression was inhibited in ASFV-infected mature bone marrow-derived macrophages, and infection with the virulent MGF360-9L gene deletion strain (∆MGF360-9L) attenuated the inhibitory effect of the wild-type strain (WT) on HAX1 expression, suggesting a complex regulatory relationship between MGF360-9L and HAX1. Furthermore, the E3 ubiquitin ligase RNF114 interacted with MGF360-9L and HAX1, MGF360-9L degraded HAX1 through the ubiquitin-proteasome pathway, and RNF114 facilitated the degradation of HAX1 by MGF360-9L-linked K48 ubiquitin chains through the ubiquitin-proteasome pathway, thereby facilitating ASFV replication. In conclusion, this study has enriched our understanding of the regulatory networks between ASFV proteins and host proteins and provided a reference for investigation into the pathogenesis and immune escape mechanism of ASFV.

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