A key anti-viral protein, RSAD2/VIPERIN, restricts the release of Measles virus in infected cells

Cheyne Kurokawa, Ianko D. Iankov, Evanthia Galanis

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

Measles virus (MV), a paramyxovirus, is one of the most contagious human pathogens and is responsible for thousands of deaths annually. Wild-type MV evolved to counter the innate immune system by avoiding both type I interferon (IFN) induction and inhibiting IFN signaling through the JAK/STAT pathway. However, virus replication is significantly inhibited in IFN-pretreated cells. Similarly, MV vaccine derived strains are inhibited by IFN pretreatment, but vaccine strains also induce IFN. Despite the significant progress in understanding the interactions between MV and the IFN pathway, the IFN stimulated genes (ISGs) that inhibit MV replication remain largely unknown. The aim of this study is to identify specific ISGs that mediate restriction of MV. In this study, we report that Radical S-adenosyl methionine domain containing 2 (RSAD2) restricts MV infection at the stage of virus release in infected 293T cells. Furthermore, attenuated MV strains are currently being developed as a novel treatment for solid and hematological malignancies. Therefore, we tested the impact of RSAD2 expression in an oncolytic virotherapy context using a MV permissive ovarian cancer line (SR-B2). As measured in 293T cells, MV release was also impaired in SR-B2 cells transduced to express RSAD2 in vitro. Additionally, oncolytic MV therapeutic efficacy was impaired in SR-B2 cells transduced to express RSAD2 in vivo. Overall, we identify RSAD2 as a novel restriction factor for MV by inhibiting the release of virus. These results provide important information regarding the interaction between MV and the innate immune system, as well as implications for the design of oncolytic MV platforms.

Original languageEnglish (US)
Pages (from-to)145-150
Number of pages6
JournalVirus Research
Volume263
DOIs
StatePublished - Apr 2 2019

Keywords

  • Antiviral
  • Interferon
  • Interferon stimulated genes
  • Measles
  • RSAD2
  • VIPERIN

ASJC Scopus subject areas

  • Virology
  • Infectious Diseases
  • Cancer Research

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