Peptidyl-prolyl cis/trans isomerase Pin1 interacts with hepatitis B virus core particle, but not with HBc protein, to promote HBV replication

Frontiers in Cellular and Infection Microbiology

Cellular and Infection Microbiology

Jaesung Jung¹  Muhammad Azhar Sajjad¹  Jiseon Ha¹  Jumi Kim¹  Chanho Song¹  Sun Park¹  Kyongmin Kim¹  Hyeonjoong Kwon¹  Ho-Joon Shin¹ 

[1] Department of Microbiology, Ajou University School of Medicine, Suwon, Republic of Korea;Department of Biomedical Science, Graduate School of Ajou University, Suwon, Republic of Korea;

关键词: hepatitis B virus;    HBV replication;    core particle;    PPIase Pin1;    Pin1-core particle interaction;   

DOI  :  10.3389/fcimb.2023.1195063

 received in 2023-03-28, accepted in 2023-06-01,  发布年份 2023

来源: Frontiers

【 摘 要 】

Here, we demonstrate that the peptidyl-prolyl cis/trans isomerase Pin1 interacts noncovalently with the hepatitis B virus (HBV) core particle through phosphorylated serine/threonine-proline (pS/TP) motifs in the carboxyl-terminal domain (CTD) but not with particle-defective, dimer-positive mutants of HBc. This suggests that neither dimers nor monomers of HBc are Pin1-binding partners. The 162TP, 164SP, and 172SP motifs within the HBc CTD are important for the Pin1/core particle interaction. Although Pin1 dissociated from core particle upon heat treatment, it was detected as an opened-up core particle, demonstrating that Pin1 binds both to the outside and the inside of the core particle. Although the amino-terminal domain S/TP motifs of HBc are not involved in the interaction, 49SP contributes to core particle stability, and 128TP might be involved in core particle assembly, as shown by the decreased core particle level of S49A mutant through repeated freeze and thaw and low-level assembly of the T128A mutant, respectively. Overexpression of Pin1 increased core particle stability through their interactions, HBV DNA synthesis, and virion secretion without concomitant increases in HBV RNA levels, indicating that Pin1 may be involved in core particle assembly and maturation, thereby promoting the later stages of the HBV life cycle. By contrast, parvulin inhibitors and PIN1 knockdown reduced HBV replication. Since more Pin1 proteins bound to immature core particles than to mature core particles, the interaction appears to depend on the stage of virus replication. Taken together, the data suggest that physical association between Pin1 and phosphorylated core particles may induce structural alterations through isomerization by Pin1, induce dephosphorylation by unidentified host phosphatases, and promote completion of virus life cycle.

【 授权许可】

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Copyright © 2023 Kwon, Kim, Song, Sajjad, Ha, Jung, Park, Shin and Kim