原创力文档a two-phase innate host response to alphavirus infection identified by mrnp-tagging in vivo两阶段的宿主应对甲病毒感染被mrnp-tagging体内.pdfVIP
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a two-phase innate host response to alphavirus infection identified by mrnp-tagging in vivo两阶段的宿主应对甲病毒感染被mrnp-tagging体内
A Two-Phase Innate Host Response
to Alphavirus Infection Identified
by mRNP-Tagging In Vivo
Jennifer L. Konopka1,2¤a*, Luiz O. Penalva3¤b, Joseph M. Thompson1,2¤c, Laura J. White1,2, Clayton W. Beard1,2¤d,
Jack D. Keene3, Robert E. Johnston1,2*
1 Department of Microbiology and Immunology University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America, 2 Carolina Vaccine Institute,
University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America, 3 Department of Molecular Genetics and Microbiology, Center for RNA
Biology, Duke University Medical Center, Durham, North Carolina, United States of America
A concept fundamental to viral pathogenesis is that infection induces specific changes within the host cell, within
specific tissues, or within the entire animal. These changes are reflected in a cascade of altered transcription patterns
evident during infection. However, elucidation of this cascade in vivo has been limited by a general inability to
distinguish changes occurring in the minority of infected cells from those in surrounding uninfected cells. To
circumvent this inherent limitation of traditional gene expression profiling methods, an innovative mRNP-tagging
technique was implemented to isolate host mRNA specifically from infected cells in vitro as well as in vivo following
Venezuelan equine encephalitis virus (VEE) infection. This technique facilitated a direct characterization of the host
defense response specifically within the first cells infected with VEE, while simultaneous total RNA analysis assessed
the collective response of both the infected and uninfected cells. The result was a unique, multifaceted profile of the
early response to VEE infection in primary dendritic cells, as well as in the draining lymph node, the initially targeted
tissue in
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