Cell-line-induced mutation of the rotavirus genome alters expression of an IRF3-interacting protein

The EMBO Journal
K KearneyJ T Patton

Abstract

Rotavirus, a cause of severe gastroenteritis, contains a segmented double-stranded (ds)RNA genome that replicates using viral mRNAs as templates. The highly conserved 3'-consensus sequence (3'CS), UGUGACC, of the mRNAs promotes dsRNA synthesis and enhances translation. We have found that the 3'CS of the gene (g5) encoding NSP1, an antagonist of interferon signaling, undergoes rapid mutation when rhesus rotavirus (RRV) is serially passaged at high multiplicity of infection (MOI) in cells permitting high titer growth. These mutations increase the promoter activity of the g5 3'-sequence, but decrease its activity as a translation enhancer. The location of the mutations defines the minimal essential promoter for dsRNA synthesis as URN0-5CC. Under passage conditions where cell-to-cell spread of the virus is required to complete infection (low MOI), the 3'CS is retained due to the need for NSP1 to be expressed at levels sufficient to prevent establishment of the antiviral state. These data demonstrate that host cell type and propagation conditions affect the capacity of RRV to produce the virulence gene product NSP1, an important consideration in producing RRV-based vaccines.

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Citations

Mar 3, 2005·Proceedings of the National Academy of Sciences of the United States of America·Mario Barro, John T Patton
Aug 29, 2009·Immunology Letters·Kaijun LiuJintao Li
Oct 23, 2016·Infection, Genetics and Evolution : Journal of Molecular Epidemiology and Evolutionary Genetics in Infectious Diseases·Takeshi Tsugawa, Hiroyuki Tsutsumi
Jan 16, 2007·Advances in Virus Research·John T PattonZenobia F Taraporewala
Jun 13, 2015·Journal of Virology·Matthieu GratiaDidier Poncet
Jan 14, 2021·Virus Research·Yuta Kanai, Takeshi Kobayashi
Jun 3, 2021·Viruses·Somya AggarwalMegan T Baldridge

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