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Composition for treating virus infection disease comprising jab1Composition for treating virus infection disease comprising jab1 description/claimsThe Patent Description & Claims data below is from USPTO Patent Application 20080095742, Composition for treating virus infection disease comprising jab1. Brief Patent Description - Full Patent Description - Patent Application Claims
TECHNICAL FIELD [0001]The present invention relates, in general, to a composition for treating a viral infection comprising Jab1. More particularly, the present invention relates to a composition for treating or preventing a viral infection comprising a Jab1(Jun-activation binding protein 1) protein, a nucleic acid having a nucleotide sequence coding for a Jab1 protein or a recombinant virus expressing a Jab1 protein. BACKGROUND ART [0002]Flavivirus and pestivirus belong to the Flaviviridae family which possesses a single-stranded positive sense RNA genome and causes various diseases in vertebrate hosts. West Nile virus (WNV) (Burt et al., Emerg Infect Dis., 8(8):820-826, 2002; Asnis et al., Clin Imfect Dis 30(3): 413-418, 2000) causes diseases including fever, rash, arthralgia and myalgia when infecting susceptible hosts. Apoptosis in wild-type WNV-infected brain cells is induced in a Bax-dependent manner (Parquet et al., FEBS Lett., 500(1-2):17-24. 2001), and the apoptosis is induced by the capsid protein of WNV through the mitochondrial/caspase-9 pathway (Yang et al., Emerg Infect Dis., 8(12):1379-1384, 2002). However, the intracellular pathological mechanism of West Nile virus infection has not been completely understood. [0003]Immunoglobulins and antiviral agents such as interferon alpha-2b and ribavirin were conventionally used for preventing and treating West Nile virus infection (Agrawal and Petersen., J Infect Dis, 188(1):1-4, 2003; Morrey et al., Antiviral Res., 55(1):107-116, 2002; Anderson et al., Emerg Infect Dis., 8(1):107-108, 2002), but they have low therapeutic effects. At present, there is no effective drug for treating or preventing West Nile virus infection. Thus, there is a need for the development of such effective drugs. [0004]On the other hand, Jab1 (Jun-activation binding protein 1) was initially known as a coactivator of AP-1 (Jun/Fos proto-oncogene) protein and has the following, various functions. Jab1 is a component (CSN5) of the COP9 signalosome (CSN) (Wei et al., Annu Rev Cell Dev Biol., 19:261-286, 2003), and Jab1/CSN5 exists in a wide spectrum of organisms, ranging from yeasts to plants and animals. Overexpression of Jab1 causes the translocation of cyclin dependent kinase inhibitor p27/Kip1 from the nucleus to the cytoplasm, accelerates the Ub-26S proteasome-dependent degradation, and participates in the G1-S transition of the cell cycle, mediated by p27/Kip1 (Tomoda et al., Nature, 398(6723):160-165, 1999). In addition, Jab1 involves the nuclear translocation of PGP9.5 that is overexpressed in primary lung cancer cells (Caballero et al., Oncogene, 21(19):3003-3010, 2002). Jab1 interacts with p53, Smad4 and lutropin/choriogonadotropin receptor and stimulates degradation of these proteins (Bech-Otschir et al., EMBO J., 20(6):1630-1639, 2001; Li et al. J Biol Chem., 275(18):13386-13393, 2000; Wan et al., EMBO J., 3(2):171-176, 2002). Taken together, Jab1 translocates proteins from the nucleus to the cytoplasm by interaction with intracellular proteins and thus stimulates protein degradation in a proteasome-dependent manner. [0005]However, there is no report for interaction between Jab1 and viral proteins upon flavivirus infection. [0006]Based on this background, the present inventors identified Jab1 as a protein interacting with the capsid protein of flavivirus, and found that Jab1 inhibits apotosis by accelerating degradation of the capsid protein and that Jab1 is useful for treating or preventing a viral infection thereby leading to the present invention. DISCLOSURE OF THE INVENTION [0007]It is therefore an object of the present invention to provide a composition for treating or preventing a flavivirus or pestivirus infection, which comprises a Jab1 (Jun-activation binding protein 1) protein. [0008]It is another object of the present invention to provide a composition for treating or preventing a flavivirus or pestivirus infection, which comprises a nucleic acid having a nucleotide sequence coding for a Jab1 protein. [0009]It is a further object of the present invention to provide a composition for treating or preventing a flavivirus or pestivirus infection, which comprises a recombinant virus expressing a Jab1 protein. [0010]It is yet another object of the present invention to provide a method of treating or preventing a flavivirus or pestivirus infection, which is based on administering a pharmaceutically effective amount of a Jab1 protein to a subject requiring treatment or prevention of a viral infection. [0011]It is still another object of the present invention to provide a method of treating or preventing a flavivirus or pestivirus infection, which is based on administering a pharmaceutically effective amount of a nucleic acid having a nucleotide sequence coding for a Jab1 protein to a subject requiring treatment or prevention of a viral infection. [0012]It is still another object of the present invention to provide a method of treating or preventing a flavivirus or pestivirus infection, which is based on administering a pharmaceutically effective amount of a recombinant virus expressing a Jab1 protein to a subject requiring treatment or prevention of a viral infection. [0013]It is still another object of the present invention to provide a method of assaying a substance stimulating expression of a Jab1 protein. BRIEF DESCRIPTION OF THE DRAWINGS [0014]The above and other objects, features and other advantages of the present invention will be more clearly understood from the following detailed description taken in conjunction with the accompanying drawings, in which: [0015]FIG. 1 shows the results of immunofluorescence analysis for expression patterns of the capsid (Cp) protein of West Nile virus (WNV) in three tumor cell lines; [0016]FIG. 2 shows the results of immunofluorescence analysis for expression patterns of WNV-Cp in SK-N-SH cells; [0017]FIG. 3 shows the results of an annexin assay, displaying apoptosis induction by WNV-Cp in two tumor cell lines; [0018]FIG. 4 shows the results of FACS analysis, displaying apoptosis induction by WNV-Cp in 293T cells; [0019]FIG. 5 shows the procedure of a yeast two hybrid assay resulting in obtainment of clones expressing proteins interacting with WNV-Cp; [0020]FIG. 6 shows the results of immunofluorescence analysis, revealing that Jab1 translocates WNV-Cp from the nucleolus to the cytoplasm; Continue reading about Composition for treating virus infection disease comprising jab1... 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