A screening for DNA damage response molecules that affect HIV-1 infection

• 新堂, 啓祐

  Department of Hematology and Oncology, Graduate School of Medicine, Kyoto University

• 永田, 佳代子

  Department of Hematology and Oncology, Graduate School of Medicine, Kyoto University

• 白川, 康太郎

  Department of Hematology and Oncology, Graduate School of Medicine, Kyoto University

• 小林, 正行

  Department of Hematology and Oncology, Graduate School of Medicine, Kyoto University

• 武田, 俊一

  Department of Hematology and Oncology, Graduate School of Medicine, Kyoto University

• 髙折, 晃史

  Department of Hematology and Oncology, Graduate School of Medicine, Kyoto University

• Shirakawa, Kotaro

  Department of Hematology and Oncology, Graduate School of Medicine, Kyoto University

• Kobayashi, Masayuki

  Department of Hematology and Oncology, Graduate School of Medicine, Kyoto University

• Takeda, Shunichi

  Department of Radiation Genetics, Graduate School of Medicine, Kyoto University

• Takaori-Kondo, Akifumi

  Department of Hematology and Oncology, Graduate School of Medicine, Kyoto University

抄録

Host DNA damage response molecules affect retroviral infection, as DNA intermediates of the viruses play essential roles in the viral life cycles. Although several such molecules have been reported, interactions between HIV-1 and host DNA damage response molecules have not been fully elucidated. To screen DNA damage response molecules that might affect HIV-1 infection, a set of 32 DNA-repair-deficient DT40 isogenic mutant cells were tested for HIV-1 infectivity. Seven out of the 32 clones showed less than 50% infectivity compared to parental DT40 cells, implying that DNA repair molecules deficient in these cells might support HIV-1 infection. Of these, EXO1 −/−, TP53BP1 −/− and WRN −/− cells showed more than twofold accumulation of two long terminal repeat circles and less than 50% integrated proviral DNA in quantitative-PCR analyses, indicating that the integration step is impaired. RAD18 −/− cells showed twofold higher HIV-1 infectivity and increased reverse transcription products at earlier time points, suggesting that RAD18 suppresses reverse transcription. The HIV-1 suppressive effects of RAD18 were confirmed by over-expression and knockdown experiments in human cells. L274P, a DNA-binding-impaired mutant of RAD18, showed impaired HIV-1 suppression and DNA binding, suggesting that binding HIV-1 DNA intermediates is critical for RAD18 to suppress reverse transcription and HIV-1 infection. Our data help understand interactions between host DNA damage response molecules and viral DNA.

収録刊行物

• Biochemical and Biophysical Research Communications

  Biochemical and Biophysical Research Communications 513 (1), 93-98, 2019-05-21

  Elsevier BV

キーワード

• Retrovirus
• Host factors
• Reverse transcription
• RAD18
• Virus-host interactions
• DNA damage response

詳細情報

• CRID: 1050001338228131072
• NII論文ID: 120006606978
• ISSN: 0006291X
• HANDLE: 2433/240925
• 本文言語コード: en
• 資料種別: journal article
• データソース種別:
  • IRDB
  • CiNii Articles