Identification and characterization of the host factors involved in the genome replication of Human papillomaviruses associated with the viral persistence

2015 Fiscal Year Final Research Report

• Project/Area Number: 25860349
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Virology
• Research Institution: National Cancer Center Japan
• Principal Investigator: Nakahara Tomomi 国立研究開発法人国立がん研究センター, 研究所, 研究員 (60601177)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: パピローマウイルス / 持続感染 / ゲノム複製 / DNA損傷修復系 / NFｋB / プロテオソーム

Outline of Final Research Achievements

High-risk Human papillomaviruses (HR-HPVs), an etiological agent of cervical cancer, undergo three phases of the viral genome replication in the viral life cycle which is tightly linked to the differentiation status of stratified squamous epithelium. The aim of this study was to elucidate molecular mechanisms for switching the viral replication in keratinocytes, host for persistent infection of HPVs. We found that E1, a viral DNA helicase, activates NF-κB through ATR pathway and this activation of NF-κB limits E1 dependent-viral replication. Thus, E1 and NF-κB form a negative feedback loop which may function as a molecular switch for the viral genome replication.

Free Research Field

ウイルス学