Multiple proteins differing between laboratory stocks of mammalian orthoreoviruses affect both virus sensitivity to interferon and induction of interferon production during infection

Delphine Lanoie; Guy Lemay

doi:10.1016/j.virusres.2018.01.009

Multiple proteins differing between laboratory stocks of mammalian orthoreoviruses affect both virus sensitivity to interferon and induction of interferon production during infection

Virus Res. 2018 Mar 2:247:40-46. doi: 10.1016/j.virusres.2018.01.009. Epub 2018 Jan 31.

Authors

Delphine Lanoie¹, Guy Lemay²

Affiliations

¹ Département de microbiologie, infectiologie et immunologie, Université de Montréal, Montréal, H3C 3J7, Canada.
² Département de microbiologie, infectiologie et immunologie, Université de Montréal, Montréal, H3C 3J7, Canada. Electronic address: guy.lemay@umontreal.ca.

PMID: 29382551
DOI: 10.1016/j.virusres.2018.01.009

Abstract

In the course of previous works, it was observed that the virus laboratory stock (T3D^S) differs in sequence from the virus encoded by the ten plasmids currently in use in many laboratories (T3D^K), and derived from a different original virus stock. Seven proteins are affected by these sequence differences. In the present study, replication of T3D^K was shown to be more sensitive to the antiviral effect of interferon. Infection by the T3D^K virus was also shown to induce the production of higher amount of β and α-interferons compared to T3D^S. Two proteins, the μ2 and λ2 proteins, were found to be responsible for increased sensitivity to interferon while both μ2 and λ1 are responsible for increased interferon secretion. Altogether this supports the idea that multiple reovirus proteins are involved in the control of induction of interferon and virus sensitivity to the interferon-induced response. While interrelated, interferon induction and sensitivity can be separated by defined gene combinations. While both μ2 and λ2 were previously suspected of a role in the control of the interferon response, other proteins are also likely involved, as first shown here for λ1. This also further stresses that due caution should be exerted when comparing different virus isolates with different genetic background.

Keywords: Interferon; Reovirus; Reverse genetics.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Antiviral Agents / pharmacology
Capsid Proteins / chemistry
Capsid Proteins / genetics*
Capsid Proteins / metabolism
Cell Line
Cricetulus
DNA-Binding Proteins / chemistry
DNA-Binding Proteins / genetics*
DNA-Binding Proteins / metabolism
Epithelial Cells / drug effects
Epithelial Cells / immunology
Epithelial Cells / virology
Fibroblasts / drug effects
Fibroblasts / immunology
Fibroblasts / virology
Gene Expression Regulation, Viral
Host-Pathogen Interactions
Interferon-alpha / biosynthesis
Interferon-alpha / pharmacology*
Interferon-beta / biosynthesis
Interferon-beta / pharmacology*
Mice
Models, Molecular
Nucleotidyltransferases / chemistry
Nucleotidyltransferases / genetics*
Nucleotidyltransferases / metabolism
Orthoreovirus, Mammalian / drug effects*
Orthoreovirus, Mammalian / genetics
Orthoreovirus, Mammalian / immunology
Protein Conformation, alpha-Helical
Protein Conformation, beta-Strand
RNA-Binding Proteins / chemistry
RNA-Binding Proteins / genetics*
RNA-Binding Proteins / metabolism
Reassortant Viruses / drug effects*
Reassortant Viruses / genetics
Reassortant Viruses / immunology
Reverse Genetics
Viral Core Proteins / chemistry
Viral Core Proteins / genetics*
Viral Core Proteins / metabolism
Viral Proteins / chemistry
Viral Proteins / genetics*
Viral Proteins / metabolism

Substances

Antiviral Agents
Capsid Proteins
DNA-Binding Proteins
Interferon-alpha
RNA-Binding Proteins
Viral Core Proteins
Viral Proteins
lambda 1 protein, reovirus
mu2 protein, Reovirus
reovirus protein lambda2
Interferon-beta
Nucleotidyltransferases