Search for transcription factors involved in latent and persistent human papillomavirus infection.

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K07047
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 49060:Virology-related
• Research Institution: National Institute of Infectious Diseases
• Principal Investigator: Ishii Yoshiyuki 国立感染症研究所, 病原体ゲノム解析研究センター, 主任研究官 (90342899)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: HPV / 持続感染 / HOXC13

Outline of Final Research Achievements

The viral genome of the high-risk human papillomavirus (HPV), the causative agent of cervical cancer, is stably maintained as extrachromosomal episomes that establish persistent infection. We previously identified transcription factor HOXC13 as an important host protein mediating the short-term retention of the HPV16 and HPV18 genomes in normal human immortalized keratinocytes (NIKS). Here, we used CRISPR-Cas9 technology to construct HOXC13 knockout (KO) NIKS cells to determine whether HOXC13 is required for the long-term maintenance of high-risk HPV genomes. HPV16, HPV18, HPV52, and HPV58 whole genomes were transfected into HOXC13 KO cells, and the copy number of viral genomes per cell was monitored over cell passages. Copy numbers of HPV16, HPV52, and HPV58 genomes decreased continuously in HOXC13 KO cells, whereas HPV18 genomes remained stable throughout passages. Thus, HOXC13 is critical for the stable maintenance of the viral genomes of HPV16, HPV52, and HPV58, but not HPV18.

Free Research Field

ウイルス学

Academic Significance and Societal Importance of the Research Achievements

本研究の成果である長期培養におけるHPV16、HPV52、HPV58のウイルスゲノムの維持にHOXC13が寄与する事実は、我々が以前提唱したHPVはHOXC13を発現する上皮幹細胞を標的とし、HOXC13依存的な初期プロモーターの活性化とウイルスゲノムの維持により持続感染を確立するとした仮説を支持している。HPV18は、HPV16、HPV52、HPV58と異なり、腺細胞指向性のようなユニークな特徴を持っている。今回のHOXC13に依存しないHPV18ゲノムの維持は、細胞指向性などHPV18の独自性を理解する上で重要な役割を果たすと考えられる。