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Nuclear Localization and Cleavage of STAT6 Is Induced by Kaposi’s Sarcoma-Associated Herpesvirus for Viral Latency
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نویسنده
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wang c. ,zhu c. ,wei f. ,gao s. ,zhang l. ,li y. ,feng y. ,tong y. ,xu j. ,wang b. ,yuan z. ,robertson e.s. ,cai q.
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منبع
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plos pathogens - 2017 - دوره : 13 - شماره : 1
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چکیده
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Emerging evidence implies that stat6 plays an important role in both the adaptive and innate immune responses to virus infection. kaposi’s sarcoma-associated herpesvirus (kshv) is an oncogenic γ-herpesvirus agent associated with several human malignancies,including kaposi’s sarcoma (ks) and primary effusion lymphomas (pels). previously,we demonstrated that kshv blocks il-4-induced stat6 phosphorylation and retains a basal il-13/stat6 constitutive activation for cell survival and proliferation. however,the mechanism by which kshv regulates stat6 remains largely unknown. here,we found that kshv-encoded lana interacts with stat6 and promotes nuclear localization of stat6 independent of the tyrosine 641-phosphorylation state. moreover,nuclear localization of stat6 is also dramatically increased in ks tissue. the latent antigen lana induces serine protease-mediated cleavage of stat6 in the nucleus,where the cleaved stat6 lacking transactivation domain functions as a dominant-negative regulator to repress transcription of replication and transcription activator (rta) and in turn shut off viral lytic replication. blockade of stat6 by small interference rna dramatically enhances expression of rta,and in turn reduces kshv-infected endothelial cell growth and colony formation. taken together,these results suggest that nuclear localization and cleavage of stat6 is important for modulating the viral latency and pathogenesis of kshv. © 2017 wang et al.
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آدرس
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moe& moh key laboratory of medical molecular virology,school of basic medicine,shanghai medical college,fudan university,shanghai, China, moe& moh key laboratory of medical molecular virology,school of basic medicine,shanghai medical college,fudan university,shanghai, China, shengyushou center of cell biology and immunology,school of life sciences and biotechnology,shanghai jiao tong university,shanghai, China, hospital and institute of obstetrics and gynecology,shanghai medical college,fudan university,shanghai, China, medical laboratory,nanchang hospital of integrative traditional chinese and western medicine,nanchang, China, moe& moh key laboratory of medical molecular virology,school of basic medicine,shanghai medical college,fudan university,shanghai, China, shanghai public health clinical center,fudan university,shanghai, China, division of hematology,shanghai first people’s hospital,shanghai jiao tong university,shanghai, China, moe& moh key laboratory of medical molecular virology,school of basic medicine,shanghai medical college,fudan university,shanghai,china,shanghai public health clinical center,fudan university,shanghai, China, moe& moh key laboratory of medical molecular virology,school of basic medicine,shanghai medical college,fudan university,shanghai, China, moe& moh key laboratory of medical molecular virology,school of basic medicine,shanghai medical college,fudan university,shanghai,china,shanghai public health clinical center,fudan university,shanghai, China, department of microbiology,perelman school of medicine,university of pennsylvania,philadelphia,pa, United States, moe& moh key laboratory of medical molecular virology,school of basic medicine,shanghai medical college,fudan university,shanghai, China
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Authors
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