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Transcriptional Correlates of Disease Outcome in Anticoagulant-Treated Non-Human Primates Infected with Ebolavirus
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نویسنده
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garamszegi s. ,yen j.y. ,honko a.n. ,geisbert j.b. ,rubins k.h. ,geisbert t.w. ,xia y. ,hensley l.e. ,connor j.h.
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منبع
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plos neglected tropical diseases - 2014 - دوره : 8 - شماره : 7
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چکیده
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Ebola virus (ebov) infection in humans and non-human primates (nhps) is highly lethal,and there is limited understanding of the mechanisms associated with pathogenesis and survival. here,we describe a transcriptomic analysis of nhps that survived lethal ebov infection,compared to nhps that did not survive. it has been previously demonstrated that anticoagulant therapeutics increase the survival rate in ebov-infected nhps,and that the characteristic transcriptional profile of immune response changes in anticoagulant-treated nhps. in order to identify transcriptional signatures that correlate with survival following ebov infection,we compared the mrna expression profile in peripheral blood mononuclear cells from ebov-infected nhps that received anticoagulant treatment,to those that did not receive treatment. we identified a small set of 20 genes that are highly confident predictors and can accurately distinguish between surviving and non-surviving animals. in addition,we identified a larger predictive signature of 238 genes that correlated with disease outcome and treatment; this latter signature was associated with a variety of host responses,such as the inflammatory response,t cell death,and inhibition of viral replication. notably,among survival-associated genes were subsets of genes that are transcriptionally regulated by (1) ccaat/enhancer-binding protein alpha,(2) tumor protein 53,and (3) megakaryoblastic leukemia 1 and myocardin-like protein 2. these pathways merit further investigation as potential transcriptional signatures of host immune response to ebov infection.
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آدرس
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bioinformatics program,boston university,boston,ma, United States, department of microbiology,school of medicine,boston university,boston,ma,united states,national emerging infectious diseases laboratories,boston university,boston,ma, United States, u.s. army medical research institute of infectious diseases,fort detrick,frederick,md, United States, department of microbiology and immunology,university of texas medical branch,galveston,tx, United States, national aeronautics and space administration,houston,tx, United States, department of microbiology and immunology,university of texas medical branch,galveston,tx, United States, bioinformatics program,boston university,boston,ma,united states,department of bioengineering,mcgill university,montreal, Canada, integrated research facility at fort detrick,national institute of allergy and infectious diseases,national institutes of health,fort detrick,frederick,md, United States, bioinformatics program,boston university,boston,ma,united states,department of microbiology,school of medicine,boston university,boston,ma,united states,national emerging infectious diseases laboratories,boston university,boston,ma, United States
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Authors
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