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Picornavirus infection enhances aspartate by the SLC38A8 transporter to promote viral replication

Huisheng Liu1, Zixiang Zhu1, Qiao Xue1

  • 1State Key Laboratory of Veterinary Etiological Biology; College of Veterinary Medicine, Lanzhou University, WOAH/National reference laboratory for foot-and-mouth disease; Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, China.

Plos Pathogens
|February 3, 2023
PubMed

Insights

Foot-and-mouth disease virus (FMDV) infection alters cellular metabolism, significantly increasing aspartate levels via the SLC38A8 transporter. This metabolic shift is crucial for viral replication in cells and mice, offering new targets for prevention.

Area of Science:

  • Virology
  • Metabolomics
  • Molecular Biology

Background:

  • Foot-and-mouth disease, caused by FMDV, is a significant animal disease.
  • Metabolic alterations during FMDV infection are not well understood.

Purpose of the Study:

  • To investigate the metabolic changes induced by FMDV infection.
  • To elucidate the role of specific metabolites and transporters in viral replication.

Main Methods:

  • Metabolomic analysis of infected cells, serum, and tonsils.
  • Investigation of amino acid transporters and signaling pathways.
  • Viral replication assays in cell cultures and mice.

Main Results:

  • FMDV infection significantly altered 284 metabolites, primarily amino acids and nucleotides.
  • Aspartate levels were elevated in FMDV-infected cells and animals, mediated by SLC38A8.
  • Other viruses (EV71, SVV) also utilize SLC38A8 to increase aspartate.
  • Aspartate and SLC38A8 are essential for FMDV, EV71, and SVV replication.
  • FMDV activates the PI3K/AKT/mTOR pathway, leading to SLC38A8 expression and enhanced viral replication.

Conclusions:

  • FMDV infection induces significant metabolic reprogramming, characterized by increased aspartate.
  • The aspartate-SLC38A8 axis is a critical host factor exploited by FMDV and other viruses for replication.
  • Targeting aspartate metabolism presents a novel strategy for controlling FMDV and related viral infections.

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