%A Nishi,Mayuko %A Miyakawa,Kei %A Matsunaga,Satoko %A Khatun,Hajera %A Yamaoka,Yutaro %A Watashi,Koichi %A Sugiyama,Masaya %A Kimura,Hirokazu %A Wakita,Takaji %A Ryo,Akihide %D 2020 %J Frontiers in Cell and Developmental Biology %C %F %G English %K virus-host interaction,Phosphorylation,prolyl isomerization,Lysosome,HBV - hepatitis B virus %Q %R 10.3389/fcell.2020.00026 %W %L %M %P %7 %8 2020-January-31 %9 Original Research %# %! Pin1 regulates HBc stability %* %< %T Prolyl Isomerase Pin1 Regulates the Stability of Hepatitis B Virus Core Protein %U https://www.frontiersin.org/articles/10.3389/fcell.2020.00026 %V 8 %0 JOURNAL ARTICLE %@ 2296-634X %X The dynamic interplay between virus and host proteins is critical for establishing efficient viral replication and virus-induced pathogenesis. Phosphorylation-dependent prolyl isomerization by Pin1 provides a unique mechanism of molecular switching to control both protein function and stability. We demonstrate here that Pin1 binds and stabilizes hepatitis B virus core protein (HBc) in a phosphorylation-dependent manner, and promotes the efficient viral propagation. Phos-tag gel electrophoresis with various site-directed mutants of HBc revealed that Thr160 and Ser162 residues within the C terminal arginine-rich domain are phosphorylated concomitantly. GST pull-down assay and co-immunoprecipitation analysis demonstrated that Pin1 associated with phosphorylated HBc at the Thr160-Pro and Ser162-Pro motifs. Chemical or genetic inhibition of Pin1 significantly accelerated the rapid degradation of HBc via a lysosome-dependent pathway. Furthermore, we found that the pyruvate dehydrogenase phosphatase catalytic subunit 2 (PDP2) could dephosphorylate HBc at the Pin1-binding sites, thereby suppressing Pin1-mediated HBc stabilization. Our findings reveal an important regulatory mechanism of HBc stability catalyzed by Pin1 and may facilitate the development of new antiviral therapeutics targeting Pin1 function.