title: The eIF4AIII RNA helicase is a critical determinant of human cytomegalovirus replication.
abstract: Human cytomegalovirus (HCMV) was recently shown to encode a large number of spliced mRNAs. While the nuclear export of unspliced viral transcripts has been extensively studied, the role of host mRNA export factors in HCMV mRNA trafficking remains poorly defined. We found that the eIF4AIII RNA helicase, a component of the exon junction complex, was necessary for efficient virus replication. Depletion of eIF4AIII limited viral DNA accumulation, export of viral mRNAs from the nucleus, and the production of progeny virus. However eIF4AIII was dispensable for the association of viral transcripts with ribosomes. We found that pateamine A, a natural compound that inhibits both eIF4AI/II and eIF4AIII, has potent antiviral activity and inhibits HCMV replication throughout the virus lytic cycle. Our results demonstrate that eIF4AIII is required for efficient HCMV replication, and suggest that eIF4A family helicases may be a new class of targets for the development of host-directed antiviral therapeutics.
authors.affiliation: Department of Microbiology & Immunology, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
authors.forename: Ben
authors.initials: B
authors.lastname: Ziehr
authors.affiliation: Department of Microbiology & Immunology, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
authors.forename: Erik
authors.initials: E
authors.lastname: Lenarcic
authors.affiliation: Department of Microbiology & Immunology, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
authors.forename: Chad
authors.initials: C
authors.lastname: Cecil
authors.affiliation: Department of Microbiology & Immunology, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. Electronic address: nmoorman@med.unc.edu.
authors.forename: Nathaniel J
authors.initials: NJ
authors.lastname: Moorman
mesh_terms: D021581:Active Transport, Cell Nucleus; D002467:Cell Nucleus / Q000821:virology; D003587:Cytomegalovirus / Q000235:genetics / Q000502:physiology*; D003586:Cytomegalovirus Infections / Q000201:enzymology* / Q000235:genetics / Q000821:virology; D039601:Eukaryotic Initiation Factor-4A / Q000235:genetics / Q000378:metabolism*; D054884:Host-Pathogen Interactions; D006801:Humans; D012367:RNA, Viral / Q000235:genetics / Q000378:metabolism; D014779:Virus Replication
chemical_list: D012367:RNA, Viral; D039601:Eukaryotic Initiation Factor-4A
keywords: Gene expression; Human cytomegalovirus; Human herpesvirus; Protein synthesis; eIF4AIII; mRNA export