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MCMV-mediated Inhibition of the Pro-apoptotic Bak Protein Is Required for Optimal in Vivo Replication
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نویسنده
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fleming p. ,kvansakul m. ,voigt v. ,kile b.t. ,kluck r.m. ,huang d.c.s. ,degli-esposti m.a. ,andoniou c.e.
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منبع
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plos pathogens - 2013 - دوره : 9 - شماره : 2
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چکیده
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Successful replication and transmission of large dna viruses such as the cytomegaloviruses (cmv) family of viruses depends on the ability to interfere with multiple aspects of the host immune response. apoptosis functions as a host innate defence mechanism against viral infection,and the capacity to interfere with this process is essential for the replication of many viruses. the bcl-2 family of proteins are the principle regulators of apoptosis,with two pro-apoptotic members,bax and bak,essential for apoptosis to proceed. the m38.5 protein encoded by murine cmv (mcmv) has been identified as bax-specific inhibitor of apoptosis. recently,m41.1,a protein product encoded by the m41 open reading frame (orf) of mcmv,has been shown to inhibit bak activity in vitro. here we show that m41.1 is critical for optimal mcmv replication in vivo. growth of a m41.1 mutant was attenuated in multiple organs,a defect that was not apparent in bak-/- mice. thus,m41.1 promotes mcmv replication by inhibiting bak-dependent apoptosis during in vivo infection. the results show that bax and bak mediate non-redundant functions during mcmv infection and that the virus produces distinct inhibitors for each protein to counter the activity of these proteins. © 2013 fleming et al.
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آدرس
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immunology and virology program,centre for ophthalmology and visual science,the university of western australia,nedlands,wa,australia,centre for experimental immunology,lions eye institute,nedlands,wa, Australia, department of biochemistry,la trobe university,melbourne,vic, Australia, immunology and virology program,centre for ophthalmology and visual science,the university of western australia,nedlands,wa,australia,centre for experimental immunology,lions eye institute,nedlands,wa, Australia, the walter and eliza hall institute of medical research,parkville,vic,australia,department of medical biology,university of melbourne,melbourne,vic, Australia, the walter and eliza hall institute of medical research,parkville,vic,australia,department of medical biology,university of melbourne,melbourne,vic, Australia, the walter and eliza hall institute of medical research,parkville,vic,australia,department of medical biology,university of melbourne,melbourne,vic, Australia, immunology and virology program,centre for ophthalmology and visual science,the university of western australia,nedlands,wa,australia,centre for experimental immunology,lions eye institute,nedlands,wa, Australia, immunology and virology program,centre for ophthalmology and visual science,the university of western australia,nedlands,wa,australia,centre for experimental immunology,lions eye institute,nedlands,wa, Australia
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Authors
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