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Journal of Virology, December 2002, p. 12676-12682, Vol. 76, No. 24
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.24.12676-12682.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Association of Mumps Virus V Protein with RACK1 Results in Dissociation of STAT-1 from the Alpha Interferon Receptor Complex

Toru Kubota,{dagger} Noriko Yokosawa, Shin-ichi Yokota, and Nobuhiro Fujii*

Department of Microbiology, School of Medicine, Sapporo Medical University, Sapporo 060-8556, Hokkaido, Japan

Received 2 May 2002/ Accepted 16 September 2002

It has been reported that mumps virus protein V or the C-terminal Cys-rich region of protein V (Vsp) is associated with blocking of the interferon (IFN) signal transduction pathway through a decrease in STAT-1 production. The intracellular target of the V protein was investigated by using a two-hybrid screening system with Vsp as bait. Full-length V protein and Vsp were able to bind to RACK1, and the interaction did not require two WD domains, WD1 and WD2, in RACK1. A significant interaction between V protein and RACK1 was also demonstrated in cells persistently infected with mumps virus (FLMT cells), and the formation of the complex was not affected by treatment with IFN. On the other hand, in uninfected cells, STAT-1 was associated with the long form of the ß subunit of the alpha IFN receptor, and this association was mediated by the function of RACK1 as an adaptor protein. Immunoprecipitation and glutathione S-transferase pull-down experiments revealed that the association of RACK1 or mumps virus V protein with the IFN receptor was undetectable in mumps virus-infected cells. Furthermore, RACK1 interacted with mumps virus V protein with a higher affinity than STAT-1 did. Therefore, it is suggested that mumps virus V protein has the ability to interact strongly with RACK1 and consequently to bring about the disruption of the complex formed from STAT-1, RACK1, and the IFN receptor.


* Corresponding author. Mailing address: Department of Microbiology, School of Medicine, Sapporo Medical University, South 1, West 17, Chou-ku, Sapporo 060-8556, Hokkaido, Japan. Phone: 81-11-611-2111, ext. 2710. Fax: 81-11-612-5861. E-mail: fujii{at}sapmed.ac.jp.

{dagger} Present address: Department of Viral Diseases and Vaccine Control, Murayama Annex, National Institute of Infectious Diseases, Musashi-Murayama, Tokyo 208-0011, Japan.


Journal of Virology, December 2002, p. 12676-12682, Vol. 76, No. 24
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.24.12676-12682.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.




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