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Interaction of E1 and hSNF5 proteins stimulates replication of human papillomavirus DNA

Nature volume 399, pages 487–491 (1999)Cite this article

Abstract

Mammalian viruses often use components of the host's cellular DNA replication machinery to carry out replication of their genomes, which enables these viruses to be used as tools for characterizing factors that are involved in cellular DNA replication. The human papillomavirus (HPV) E1 protein is essential for replication of the virus DNA1,2,3. Here we identify the cellular factor that participates in viral DNA replication by using a two-hybrid assay4 in the yeast Saccharomyces cerevisiae and E1 protein as bait. Using this assay, we isolated Ini1/hSNF5 (ref. 5), a component of the SWI/SNF complex which facilitates transcription by altering the structure of chromatin6. In vitro binding and immunoprecipitation confirmed that E1 interacts directly with Ini1/hSNF5. Transient DNA-replication assay revealed that HPV DNA replication is stimulated in a dose-dependent manner by addition of Ini1/hSNF5, and that Ini1/hSNF5 antisense RNA blocks the replication of HPV DNA. Amino-acid substitution at residues that are conserved among E1 proteins prevented the E1-Ini1/hSNF5 interaction and reduced DNA replication of HPV in vivo. Our results indicate that Ini1/hSNF5 is required for the efficient replication of papillomavirus DNA and is therefore needed, either alone or in complex with SWI/SNF complex, for mammalian DNA replication as well.

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Figure 1: Interaction between HPV-18 E1 and Ini1/hSNF5 proteins.
Figure 2: Interaction of HPV and BPV E1 proteins with Ini1/hSNF5.
Figure 3: Association of HPV-18 E1 and Ini1/hSNF5 proteins in vivo.
Figure 4: The domain of Ini1/hSNF5 required for binding to full-length HPV-18 E1.
Figure 5: The effects of Ini1/hSNF5 on papillomavirus DNA replication.
Figure 6: Amino-acid substitutions at conserved residues of E1 proteins prevent E1–Ini1/hSNF5 interaction.

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Acknowledgements

This work was supported by the Korea Science and Engineering Foundation through the Research Center for Cell Differentiation at Seoul National University and the Academic Research Fund of the Ministry of Education, Republic of Korea. J.C. holds a basic science promotion research grant from KAIST/Samsung Advanced Institute of Technology.

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  1. Joonho Choe: Correspondence and requests for materials should be addressed to J.C.

Authors and Affiliations

  1. Department of Biological Sciences, Korea Advanced Institute of Science and Technology, 305-701, Taejon, Korea

    Daeyoup Lee, Hekwang Sohn, Joonho Choe & Joonho Choe

  2. Department of Molecular Genetics, Albert Einstein College of Medicine, Bronx, 10461, New York, USA

    Ganjam V. Kalpana

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Correspondence to Joonho Choe.

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Lee, D., Sohn, H., Kalpana, G. et al. Interaction of E1 and hSNF5 proteins stimulates replication of human papillomavirus DNA. Nature 399, 487–491 (1999). https://doi.org/10.1038/20966

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