Effect of strain variations on lassa virus Z protein-mediated human RIG-I inhibition

Research output: Contribution to journalArticlepeer-review

Abstract

Mammarenaviruses include several known human pathogens, such as the prototypic lymphocytic choriomeningitis virus (LCMV) that can cause neurological diseases and Lassa virus (LASV) that causes endemic hemorrhagic fever infection. LASV-infected patients show diverse clinical manifestations ranging from asymptomatic infection to hemorrhage, multi-organ failures and death, the mechanisms of which have not been well characterized. We have previously shown that the matrix protein Z of pathogenic arenaviruses, including LASV and LCMV, can strongly inhibit the ability of the innate immune protein RIG-I to suppress type I interferon (IFN-I) expression, which serves as a mechanism of viral immune evasion and virulence. Here, we show that Z proteins of diverse LASV isolates derived from rodents and humans have a high degree of sequence variations at their N- and C-terminal regions and produce variable degrees of inhibition of human RIG-I (hRIG-I) function in an established IFN-β promoter-driven luciferase (LUC) reporter assay. Additionally, we show that Z proteins of four known LCMV strains can also inhibit hRIG-I at variable degrees of efficiency. Collectively, our results confirm that Z proteins of pathogenic LASV and LCMV can inhibit hRIG-I and suggest that strain variations of the Z proteins can influence their efficiency to suppress host innate immunity that might contribute to viral virulence and disease heterogeneity.

Original languageEnglish (US)
Article number907
JournalViruses
Volume12
Issue number9
DOIs
StatePublished - Sep 2020

Bibliographical note

Funding Information:
Funding: This research was funded by National Institute of Health (NIH), grant number R01 AI131586 to H.L. and Y.L. M.B. was supported in part by a NIH pre-doctoral T32 fellowship DA007097.

Keywords

  • Arenavirus
  • Immune evasion
  • Innate immunity
  • LCMV
  • Lassa virus
  • RIG-I
  • Sequence variations
  • Z protein

PubMed: MeSH publication types

  • Journal Article
  • Research Support, N.I.H., Extramural

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