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A novel KRAB-Zinc finger protein interacts with latency-associated nuclear antigen of Kaposi’s sarcoma-associated herpesvirus and activates transcription via terminal repeat sequences

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Abstract

Kaposi’s sarcoma-associated herpesvirus (KSHV) establishes latent infection in various cells in vitro as well as KSHV-associated tumor cells in vivo. The latency-associated nuclear antigen (LANA) of KSHV is one of a small number of genes expressed in the latent phase of KSHV infection. This antigen is crucial for establishment of the latent infection, such as replication of KSHV genomic DNA and maintenance of infection via direct interaction with terminal repeats (TRs) in the viral genome. Using a yeast two-hybrid screening method, we isolated a novel LANA-interacting protein (designated as KZLP; KRAB Zinc finger LANA interacting Protein) from a human peripheral leukocyte cDNA library. KZLP encodes a KRAB domain and 12 Kruppel-type zinc fingers. Reverse transcription polymerase chain reaction showed that KZLP was expressed ubiquitously in various cell lines including those infected with KSHV. A luciferase assay showed that KZLP could activate the KSHV open reading frame K1 promoter containing TRs in 293T cells, and that such activation required multiple TR sequences. In contrast, LANA repressed the activity of the K1 promoter through TRs, and again this repression required multiple TR units. Moreover, LANA almost completely abrogated the KZLP-mediated transcriptional activation. Our results suggest that KZLP and LANA regulate gene expression through TRs in the KSHV viral genome, including the K1 gene in latent KSHV-infected cells.

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Acknowledgments

We thank Sayoko Takizawa, and Chika Yamamoto for the excellent technical assistance. This work was supported in part by a Grant-in-Aid for Scientific Research of Japan and Grant for Promotion of Niigata University Research Projects.

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Authors and Affiliations

  1. Division of Virology, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi-Dori, Niigata, 951-8510, Japan

    Akiko Watanabe, Masaya Higuchi, Toshiaki Ohsawa, Masahiko Takahashi, Masayasu Oie & Masahiro Fujii

  2. Department of Infectious Diseases and Tropical Medicine, Research Institute, International Medical Center of Japan, 1-21-1 Toyama, Shinjuku-ku, Tokyo, 162-8655, Japan

    Masaya Fukushi

Authors
  1. Akiko Watanabe
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  2. Masaya Higuchi
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  3. Masaya Fukushi
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  4. Toshiaki Ohsawa
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  5. Masahiko Takahashi
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  6. Masayasu Oie
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  7. Masahiro Fujii
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Correspondence to Masahiro Fujii.

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Watanabe, A., Higuchi, M., Fukushi, M. et al. A novel KRAB-Zinc finger protein interacts with latency-associated nuclear antigen of Kaposi’s sarcoma-associated herpesvirus and activates transcription via terminal repeat sequences. Virus Genes 34, 127–136 (2007). https://doi.org/10.1007/s11262-006-0048-x

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  • DOI: https://doi.org/10.1007/s11262-006-0048-x

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