2013 International Interscience Conference on Infection & Chemotherapy, 2013, 02, 149-149

Hantaan virus nucleocapsid protein stimulates MDM2-dependent p53 degradation

SunWhan Park, MyungGuk Han, Chan Park, Jungsang Ryou

Abstract

Background
Nucleocapsid (N) protein of Hantaan virus (HTNV), that causes hemorrhagic fever with renal syndrome, is the most abundantly expressed protein in HTNV-infected cells. The influence of N protein to the HTNV-infected cells was not much studied yet. Recently, some evidences were reported that the N protein of HTNV inhibited apoptosis.
Methods & Results
To elucidate the regulation of apoptosis by N protein we studied p53 regulation by HTNV N protein. The amount of p53, increased by cytotoxic drugs (cisplatin, doxorubicin), was reduced when cells were infected with HTNV or over-expressed with HTNV N protein. We showed the p53 gene tran level was not affected by N protein. When cells treated with a proteasome inhibitor (MG132) or a MDM2 antagonist (Nutlin-3), p53 was not reduced in N protein-overexpressed cells. We have finally concluded the HTNV N protein ubiquitinates and degradates p53 MDM2-dependently. Interestingly a non-pathogenic hantavirus, Prospect Hill virus, did not reduced p53 level unlike pathogenic hantaviruses.
Conclusion(s)
For the first time, herein, we report down-regulation of p53 through a post-tranional mechanism by the HTNV N protein. MDM2-dependent ubiquitination of p53 was involved in the decrease of the protein. A molecular mechanism of hemorrhagic fever with renal syndrome by HTNV is proposed with this noble function of the HTNV N protein.

Keywords: Hantaan virus, p53, Apoptosis, Ubiquitination, MDM2

• 본 연구는 질병관리본부 연구개발과제(과제번호 2011-N53001-00) 연구비를 지원받아 수행되었습니다.
• This research was supported by a fund(code 2011-N53001-00) by Research of Korea Centers for Disease Control and Prevention.