title: Deep sequencing identifies noncanonical editing of Ebola and Marburg virus RNAs in infected cells.
abstract: Deep sequencing of RNAs produced by Zaire ebolavirus (EBOV) or the Angola strain of Marburgvirus (MARV-Ang) identified novel viral and cellular mechanisms that diversify the coding and noncoding sequences of viral mRNAs and genomic RNAs. We identified previously undescribed sites within the EBOV and MARV-Ang mRNAs where apparent cotranscriptional editing has resulted in the addition of non-template-encoded residues within the EBOV glycoprotein (GP) mRNA, the MARV-Ang nucleoprotein (NP) mRNA, and the MARV-Ang polymerase (L) mRNA, such that novel viral translation products could be produced. Further, we found that the well-characterized EBOV GP mRNA editing site is modified at a high frequency during viral genome RNA replication. Additionally, editing hot spots representing sites of apparent adenosine deaminase activity were found in the MARV-Ang NP 3'-untranslated region. These studies identify novel filovirus-host interactions and reveal production of a greater diversity of filoviral gene products than was previously appreciated.
  
  
  OBJECTIVE
  This study identifies novel mechanisms that alter the protein coding capacities of Ebola and Marburg virus mRNAs. Therefore, filovirus gene expression is more complex and diverse than previously recognized. These observations suggest new directions in understanding the regulation of filovirus gene expression.
authors.forename: Reed S
authors.initials: RS
authors.lastname: Shabman
authors.affiliation: Institute for Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
authors.forename: Omar J
authors.initials: OJ
authors.lastname: Jabado
authors.affiliation: Department of Microbiology and Immunology, Galveston National Laboratory, University of Texas Medical Branch, Galveston, Texas, USA.
authors.forename: Chad E
authors.initials: CE
authors.lastname: Mire
authors.affiliation: Virology Group, J. Craig Venter Institute, Rockville, Maryland, USA.
authors.forename: Timothy B
authors.initials: TB
authors.lastname: Stockwell
authors.affiliation: Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
authors.forename: Megan
authors.initials: M
authors.lastname: Edwards
authors.affiliation: Institute for Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
authors.forename: Milind
authors.initials: M
authors.lastname: Mahajan
authors.affiliation: Department of Microbiology and Immunology, Galveston National Laboratory, University of Texas Medical Branch, Galveston, Texas, USA.
authors.forename: Thomas W
authors.initials: TW
authors.lastname: Geisbert
authors.affiliation: Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, New York, USA chris.basler@mssm.edu.
authors.forename: Christopher F
authors.initials: CF
authors.lastname: Basler
mesh_terms: D000818:Animals; D002460:Cell Line; D002522:Chlorocebus aethiops; D029043:Ebolavirus / Q000235:genetics* / Q000502:physiology; D059014:High-Throughput Nucleotide Sequencing; D054884:Host-Pathogen Interactions; D006801:Humans; D029024:Marburgvirus / Q000235:genetics* / Q000502:physiology; D008969:Molecular Sequence Data; D017393:RNA Editing; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D012367:RNA, Viral / Q000235:genetics / Q000378:metabolism; D017422:Sequence Analysis, DNA; D014779:Virus Replication
chemical_list: D012333:RNA, Messenger; D012367:RNA, Viral