Cell-line-induced mutation of the rotavirus genome alters expression of an IRF3-interacting protein
Karen Kearney,Dayue Chen,Zenobia F. Taraporewala,Patrice Vende,Yasutaka Hoshino,Maria Alejandra Tortorici,Mario Barro,John T. Patton +7 more
TLDR
It is 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.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.read more
Citations
More filters
Journal ArticleDOI
Rotavirus nonstructural protein 1 subverts innate immune response by inducing degradation of IFN regulatory factor 3.
Mario Barro,John T. Patton +1 more
TL;DR: It is determined that the rotavirus gene 5 product, nonstructural protein 1 (NSP1), interacts with IRF3 in the infected cell and that wild-type NSP1 is an antagonist of the IFN-signaling pathway.
Journal ArticleDOI
Rotavirus NSP1 Inhibits Expression of Type I Interferon by Antagonizing the Function of Interferon Regulatory Factors IRF3, IRF5, and IRF7
Mario Barro,John T. Patton +1 more
TL;DR: It is determined that, in comparison to wild-type rotavirus NSP1 grow to lower titers in some cell lines and that this poor growth phenotype is due to their failure to suppress IFN expression, and evidence is provided that rotaviruses encoding wild- type N SP1 subvert IFN signaling by inducing the degradation of not only IRF3, but also IRF7.
Journal ArticleDOI
IRF3 Inhibition by Rotavirus NSP1 Is Host Cell and Virus Strain Dependent but Independent of NSP1 Proteasomal Degradation
TL;DR: NSP1's ability to degrade IRF3 is host cell dependent and is independent of NSP1 proteasomal degradation, a finding further supported using adenovirus-expressed N SP1 from NCDV bovine rotavirus.
Journal ArticleDOI
A base-specific recognition signal in the 5′ consensus sequence of rotavirus plus-strand RNAs promotes replication of the double-stranded RNA genome segments
TL;DR: It is suggested that rotavirus (+)RNA cyclization, although likely initiated by 5'- 3' nucleotide complementarity, may be stabilized by RdRP-dependent bridging.
Book ChapterDOI
Coupling of rotavirus genome replication and capsid assembly.
TL;DR: Insight into the replication mechanism has been provided from studies on Rotavirus, a member of the Reoviridae whose RdRP can specifically recognize viral plus (+) strand RNAs and catalyze their replication to dsRNAs in vitro.
References
More filters
Journal ArticleDOI
Global Illness and Deaths Caused by Rotavirus Disease in Children
TL;DR: The tremendous incidence of rotavirus disease underscores the urgent need for interventions, such as vaccines, to prevent childhood deaths in developing nations.
Journal ArticleDOI
Rotavirus RNA‐binding protein NSP3 interacts with eIF4GI and evicts the poly(A) binding protein from eIF4F
TL;DR: It is shown that a physical link between the 5′ and the 3′ ends of mRNA is necessary for the efficient translation of viral mRNAs and strongly support the closed loop model for the initiation of translation.
Journal ArticleDOI
Three-dimensional structure of rotavirus.
TL;DR: The three-dimensional structures of double and single-shelled simian rotavirus have been determined to a resolution of 40 A by image processing electron micrographs of unstained, unfixed virus particles embedded in vitreous ice and it is demonstrated that the icosahedral surface lattices in these structures have a triangulation number of 13 in a left-handed configuration.
Journal ArticleDOI
Triggering the interferon response: the role of IRF-3 transcription factor.
John Hiscott,Paula M. Pitha,Pierre Génin,Hannah Nguyen,Christophe Heylbroeck,Yael Mamane,Michèle Algarté,Rongtuan Lin +7 more
TL;DR: Recent investigations provide the framework for a model in which virus-dependent phosphorylation of IRF-3 alters protein conformation to permit nuclear translocation, association with transcriptional partners, and primary activation of IFN and IFN-responsive genes.
Journal ArticleDOI
Rotavirus vaccines: an overview.
TL;DR: The greatest experience with a multivalent vaccine to date has been gained with the quadrivalent preparation containing RRV (VP7 serotype 3) and human-RRV reassortants of VP7 serotypes 1, 2, and 4 specificity.
Related Papers (5)
Rotavirus nonstructural protein 1 subverts innate immune response by inducing degradation of IFN regulatory factor 3.
Mario Barro,John T. Patton +1 more
Safety and Efficacy of an Attenuated Vaccine against Severe Rotavirus Gastroenteritis
Guillermo M. Ruiz-Palacios,Irene Pérez-Schael,F. Raúl Velázquez,Hector Abate,Thomas Breuer,Sue Ann Costa Clemens,Brigitte Cheuvart,Felix Espinoza,Paul Gillard,Bruce L. Innis,Yolanda Cervantes,Alexandre da Costa Linhares,Pio Lopez,Mercedes Macias-Parra,Eduardo Ortega-Barria,Vesta Richardson,Doris Maribel Rivera-Medina,Luis Rivera,Belén Salinas,Noris Pavía-Ruz,Jorge Salmerón,Ricardo Rüttimann,Juan Carlos Tinoco,Pilar Rubio,Ernesto Nuñez,M. Lourdes Guerrero,Juan Pablo Yarzabal,Silvia Damaso,Nadia Tornieporth,Xavier Sáez-Llorens,Rodrigo Vergara,Timo Vesikari,Alain Bouckenooghe,Ralf Clemens,Beatrice De Vos,Miguel O'Ryan +35 more