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Swine Promyelocytic Leukemia Isoform II Inhibits Pseudorabies Virus Infection by Suppressing Viral Gene Transcription in PML-NBs

By Cuilian Yu, Aotian Xu, Yue Lang, Chao Qin, Xiufang Yuan, Wenhai Feng, Mengdong Wang, Chao Gao, Jinwen Chen, Rui Zhang, Jun Tang

Posted 25 Mar 2020
bioRxiv DOI: 10.1101/2020.03.23.004697 (published DOI: 10.1128/JVI.01197-20)

Promyelocytic leukaemia nuclear bodies (PML-NBs) possess an important intrinsic antiviral activity against a-herpesvirus infection. PML is the structural backbone of NBs, comprising different isoforms. However, the contribution of each isoform to a-herpesvirus restriction is not well understood. Here, we report the role of PML-NBs and swine PML (sPML) isoforms in pseudorabies virus (PRV) infection in its natural host swine cells. We found that sPML-NBs exhibit an anti-PRV activity in the context of increasing the expression level of endogenous sPML. Of four sPML isoforms cloned and examined, only isoform sPML-II/IIa, not sPML-I and IVa, expressed in a sPML knockout cells inhibits PRV infection. Both the unique 7b region of sPML-II and sumoylation-dependent normal formation of PML-NBs are required. 7b possesses a transcriptional repression activity and suppresses viral gene transcription during PRV infection with the cysteine residue 589 and 599 being critically involved. We conclude that sPML-NBs inhibit PRV infection by repressing viral gene transcription through the 7b region of sPML-II.

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