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Cell-cell fusion induced by reovirus FAST proteins enhances replication and pathogenicity of non-enveloped dsRNA

Yuta Kanai1, Takahiro Kawagishi1, Yusuke Sakai2

  • 1Department of Virology, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan.

Plos Pathogens
|April 26, 2019
PubMed

Insights

Fusion-associated small transmembrane (FAST) protein enhances non-enveloped virus replication and pathogenicity. FAST protein deficiency impairs viral spread and virulence but confers protection against homologous virus challenge.

Area of Science:

  • Virology
  • Cell Biology
  • Immunology

Background:

  • Non-enveloped viruses typically lack fusogenic proteins.
  • Fusion-associated small transmembrane (FAST) protein induces cell-cell fusion in reoviruses.
  • The role of FAST protein in viral replication and pathogenesis remains unclear.

Purpose of the Study:

  • To investigate the function of FAST protein in reovirus replication and pathogenicity.
  • To determine if FAST protein is essential for viral replication.
  • To evaluate the potential of FAST protein-deficient viruses as vaccine candidates.

Main Methods:

  • Generation of replication-competent, FAST protein-deficient pteropine orthoreovirus.
  • In vitro assays to assess viral replication and cell-cell fusion.
  • In vivo studies using a mouse model to evaluate viral replication, pathogenicity, and protective immunity.

Main Results:

  • FAST protein is not essential for viral replication but enhances early-phase replication.
  • Recombinant FAST protein enhances replication of FAST-deficient and other non-fusogenic viruses in a fusion-dependent manner.
  • FAST protein deficiency severely impairs viral replication and pathogenicity in mice.
  • FAST-deficient virus confers protection against lethal homologous virus challenge.

Conclusions:

  • FAST protein plays a crucial role in reovirus pathogenicity and viral spread.
  • A cell-cell fusion-dependent replication system exists in non-enveloped viruses.
  • FAST protein-deficient reoviruses are promising candidates for live-attenuated vaccines.

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