Dense Granule Protein-7 (GRA-7) of Toxoplasma gondii inhibits viral replication in vitro and in vivo

J Microbiol. 2017 Nov;55(11):909-917. doi: 10.1007/s12275-017-7392-5. Epub 2017 Oct 27.

Abstract

Dense granule protein-7 (GRA-7) is an excretory protein of Toxoplasma gondii. It is a potential serodiagnostic marker and vaccine candidate for toxoplasmosis. Previous reports demonstrated that GRA-7 induces innate immune responses in macrophages by interacting with TRAF6 via the MyD88-dependent pathway. In the present study, we evaluated the antiviral activity and induction of an antiviral state by GRA-7 both in vitro and in vivo. It was observed that GRA-7 markedly reduced the replication of vesicular stomatitis virus (VSV-GFP), influenza A virus (PR8-GFP), coxsackievirus (H3-GFP), herpes simplex virus (HSV-GFP), and adenovirus-GFP in epithelial (HEK293T/HeLa) and immune (RAW264.7) cells. These antiviral activities of GRA-7 were attributed to the induction of type I interferon (IFN) signaling, resulting in the secretion of IFNs and pro-inflammatory cytokines. Additionally, in BALB/c mice, intranasal administration of GRA-7 prevented lethal infection by influenza A virus (H1N1) and exhibited prophylactic effects against respiratory syncytial virus (RSV-GFP). Collectively, these results suggested that GRA-7 exhibits immunostimulatory and broad spectrum antiviral activities via type I IFN signaling. Thus, GRA-7 can be potentially used as a vaccine adjuvant or as a candidate drug with prophylactic potential against viruses.

Keywords: GRA-7; Toxoplasma gondii; antiviral activity.

MeSH terms

  • Animals
  • Antiviral Agents / administration & dosage
  • Antiviral Agents / pharmacology
  • Cytokines
  • Enterovirus / drug effects
  • Female
  • HEK293 Cells
  • HeLa Cells
  • Humans
  • Influenza A Virus, H1N1 Subtype / drug effects
  • Influenza A virus / drug effects
  • Influenza, Human / drug therapy
  • Influenza, Human / virology
  • Interferon Type I / immunology
  • Mice
  • Mice, Inbred BALB C
  • Orthomyxoviridae Infections / drug therapy
  • Orthomyxoviridae Infections / prevention & control
  • Orthomyxoviridae Infections / virology
  • Protozoan Proteins / isolation & purification
  • Protozoan Proteins / pharmacology*
  • Respiratory Syncytial Virus Infections / prevention & control
  • Respiratory Syncytial Virus Infections / virology
  • Simplexvirus / drug effects
  • Toxoplasma / chemistry*
  • Vesiculovirus / drug effects
  • Virus Diseases / prevention & control
  • Virus Diseases / virology
  • Virus Replication / drug effects*
  • Viruses / drug effects*

Substances

  • Antiviral Agents
  • Cytokines
  • Interferon Type I
  • Protozoan Proteins