Modeling senecavirus a replication in immortalized porcine alveolar macrophages triggers a robust interferon-mediated immune response that conversely constrains viral replication

Virology. 2023 Jan:578:141-153. doi: 10.1016/j.virol.2022.12.001. Epub 2022 Dec 17.

Abstract

Senecavirus A (SVA) is a newly emerging causative agent of vesicular diseases in swine characterized with wide genetic diversity and rapid evolution. The lack of immunologically active cell culture model impedes the study of SVA-specific innate immunity. Here, an immortalized porcine alveolar macrophages 3D4/21 strongly and productively supported replication of two SVA strains. To elaborate global and dynamic host immune response, we demonstrated that 3D4/21 intrinsically expressed canonical ISGs which were important for pre-empting viral infection. Moreover, 3D4/21 were constitutively abundant in RIG-I-like receptors (RLRs) RIG-I and MDA5 necessary for sensing RNA virus infection, thereby enabling 3D4/21 cells to establish persistent and efficient antiviral status, in particular the most dramatic and sustained expression of type I/II interferons and inflammatory and innate immune genes critical for constraining SVA replication. Our study reveals a pivotal regulatory connection between virus and host that points to the SVA pathogenesis and potential vaccine development.

Keywords: 3D4/21; IFN response; Innate immune response; RNA-seq; Senecavirus A.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • Immunity, Innate
  • Interferon Type I*
  • Macrophages, Alveolar*
  • Swine
  • Virus Replication

Substances

  • Interferon Type I

Supplementary concepts

  • Senecavirus A