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Identification Of Interaction Domains In The Pseudorabies Virus Ribonucleotide Reductase Large And Small Subunits

文献类型： 外文期刊

作者： Lyu, C; Li, WD; Peng, JM; Cai, XH

作者机构：

关键词： Pul39; Pul40; Rnr; Alphaherpesvirus; Dntps

期刊名称： VETERINARY MICROBIOLOGY

ISSN： 0378-1135

年卷期： 2020 年 246 卷

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收录情况： JCR（2021版）

摘要： Alphaherpesviral ribonucleotide reductase (RNR) is composed of large (pUL39, RR1) and small (pUL40, RR2) subunits. This enzyme can catalyze conversion of ribonucleotide to deoxynucleotide diphosphates that are further phosphorylated into deoxynucleotide triphosphate (dNTPs). The dNTPs are substrates for de novo viral DNA synthesis in infected host cells. The enzymatic activity of RNR depends on association between RR1 and RR2. However, the molecular basis underlying alphaherpesviral RNR complex formation is still largely unknown. In the current study, we investigated the pseudorabies virus (PRV) RNR interaction domains in pUL39 and pUL40. The interaction of pUL39 and pUL40 was identified by co-immunoprecipitation (co-IP) and colocalization analyses. Furthermore, the interaction amino acid (aa) domains in pUL39 and pUL40 were mapped using a series of truncated proteins. Consequently, the 90-210 aa in pUL39 was identified to be responsible for the interaction with pUL40. In turn, the 66-152, 218-258 and 280-303 aa in pUL40 could interact with pUL39, respectively. Deletion of 90-210 aa in pUL39 completely abrogated the interaction with pUL40. Deletion of 66-152, 218-258 and 280-303 aa in pUL40 remarkably weakened the interaction with pUL39, whereas a weak interaction could still be observed. Amino acid sequence alignments showed that the interaction domains identified in PRV pUL39/pUL40 were relatively non-conserved among the selected RNR subunits in alphaherpesviruses HSV1, HSV2, HHV3(VZV), BHV1, EHV1 and DEV. However, they were relatively conserved among PRV, HSV1 and HSV2. Collectively, our findings provided some molecular targets for inhibition of pUL39-pUL40 interaction to antagonize viral replication in PRV infected hosts.

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