The eIF4AIII RNA helicase is a critical determinant of human cytomegalovirus replication

Virology
Ben ZiehrNathaniel J Moorman

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.

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Citations

Feb 27, 2017·Molecular & Cellular Proteomics : MCP·Kyle C ArendNathaniel J Moorman
Aug 28, 2019·Nature Biotechnology·Angela WahlJ Victor Garcia
Jul 4, 2017·Nature Reviews. Immunology·Craig McCormick, Denys A Khaperskyy
May 27, 2021·Cancer Cell International·Yitong LiuChengkun Wang
Jul 31, 2018·Journal of the American Chemical Society·Chun-Xiang Zhuo, Alois Fürstner

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