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T Cell Inactivation by Poxviral B22 Family Proteins Increases Viral Virulence
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نویسنده
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alzhanova d. ,hammarlund e. ,reed j. ,meermeier e. ,rawlings s. ,ray c.a. ,edwards d.m. ,bimber b. ,legasse a. ,planer s. ,sprague j. ,axthelm m.k. ,pickup d.j. ,lewinsohn d.m. ,gold m.c. ,wong s.w. ,sacha j.b. ,slifka m.k. ,früh k.
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منبع
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plos pathogens - 2014 - دوره : 10 - شماره : 5
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چکیده
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Infections with monkeypox,cowpox and weaponized variola virus remain a threat to the increasingly unvaccinated human population,but little is known about their mechanisms of virulence and immune evasion. we now demonstrate that b22 proteins,encoded by the largest genes of these viruses,render human t cells unresponsive to stimulation of the t cell receptor by mhc-dependent antigen presentation or by mhc-independent stimulation. in contrast,stimuli that bypass tcr-signaling are not inhibited. in a non-human primate model of monkeypox,virus lacking the b22r homologue (mpxvδ197) caused only mild disease with lower viremia and cutaneous pox lesions compared to wild type mpxv which caused high viremia,morbidity and mortality. since mpxvδ197-infected animals displayed accelerated t cell responses and less t cell dysregulation than mpxv us2003,we conclude that b22 family proteins cause viral virulence by suppressing t cell control of viral dissemination.
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آدرس
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vaccine and gene therapy institute,oregon national primate research center,portland,or, United States, division of neuroscience,oregon national primate research center,portland,or, United States, vaccine and gene therapy institute,oregon national primate research center,portland,or, United States, department of pulmonary and critical care medicine,oregon health and science university,portland,or,united states,portland veterans administration medical center,portland,or, United States, vaccine and gene therapy institute,oregon national primate research center,portland,or, United States, department of molecular genetics and microbiology,duke university medical center,durham,nc, United States, vaccine and gene therapy institute,oregon national primate research center,portland,or, United States, division of pathobiology and immunology,oregon national primate research center,portland,or, United States, division of pathobiology and immunology,oregon national primate research center,portland,or, United States, division of pathobiology and immunology,oregon national primate research center,portland,or, United States, vaccine and gene therapy institute,oregon national primate research center,portland,or, United States, vaccine and gene therapy institute,oregon national primate research center,portland,or,united states,division of pathobiology and immunology,oregon national primate research center,portland,or, United States, department of molecular genetics and microbiology,duke university medical center,durham,nc, United States, department of pulmonary and critical care medicine,oregon health and science university,portland,or,united states,portland veterans administration medical center,portland,or, United States, department of pulmonary and critical care medicine,oregon health and science university,portland,or,united states,portland veterans administration medical center,portland,or, United States, vaccine and gene therapy institute,oregon national primate research center,portland,or,united states,division of pathobiology and immunology,oregon national primate research center,portland,or, United States, vaccine and gene therapy institute,oregon national primate research center,portland,or,united states,division of pathobiology and immunology,oregon national primate research center,portland,or, United States, division of neuroscience,oregon national primate research center,portland,or, United States, vaccine and gene therapy institute,oregon national primate research center,portland,or,united states,division of pathobiology and immunology,oregon national primate research center,portland,or, United States
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Authors
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