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Positive and negative regulation of adenovirus infection by CAR-like soluble protein, CLSP

Gene Therapy volume 14, pages 1199–1207 (2007)Cite this article

Abstract

Coxsackievirus and adenovirus receptor (CAR) is a member of the immunoglobulin (Ig) superfamily and a component of epithelial tight junction. CAR also functions as a primary receptor for coxsackievirus B and adenovirus (Ad) infection. In this study, we report the identification of a novel protein, CAR-like soluble protein (CLSP), which is closely related to CAR. Mouse CLSP (mCLSP) was composed of 390 amino acids, including three Ig domains, and showed strong homology to the IgV domain of CAR. Interestingly, mCLSP lacks a transmembrane domain, indicating that this is a soluble protein. mCLSP mRNA was detected primarily in the brain and ovary. When mCLSP cDNA was introduced into SK HEP-1 cells, which were known to be CAR positive and easily infected with Ad vector, the infection with Ad vector was severely inhibited. On the other hand, mCLSP promoted the infection with Ad vector in CAR-negative NIH3T3 cells. Furthermore, recombinant CLSP directly bound to Ad and inhibited the Ad vector-mediated transduction in SK HEP-1 cells. Computational analysis for a genome database showed that the CLSP gene is rodent-specific, and that human and bovine lack this gene. These results suggest that CLSP may play a role in the antiviral defense of the host in rodent animals.

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Acknowledgements

We thank Takashi Fukushima for expert assistance with tissue culture and immunoblotting. This work was supported by Grants-in-Aid for Exploratory Research from the Ministry of Education, Culture, Sports, and Technology of Japan and by grants for Health and Labour Sciences Research from the Ministry of Health, Labour and Welfare of Japan.

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Authors and Affiliations

  1. Laboratory of Gene Transfer and Regulation, National Institute of Biomedical Innovation, Osaka, Japan

    K Kawabata, K Tashiro, F Sakurai & H Mizuguchi

  2. Graduate School of Pharmaceutical Sciences, Osaka University, Osaka, Japan

    K Tashiro, K Yamanishi & H Mizuguchi

  3. Laboratory of Genetic Resources, National Institute of Biomedical Innovation, Osaka, Japan

    N Osada & J Kusuda

  4. Pharmaceutics and Medical Devices Agency, Tokyo, Japan

    T Hayakawa

  5. National Institute of Biomedical Innovation, Osaka, Japan

    K Yamanishi

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  1. K Kawabata
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Correspondence to H Mizuguchi.

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Kawabata, K., Tashiro, K., Sakurai, F. et al. Positive and negative regulation of adenovirus infection by CAR-like soluble protein, CLSP. Gene Ther 14, 1199–1207 (2007). https://doi.org/10.1038/sj.gt.3302975

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