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Related Experiment Video

Updated: May 23, 2025

siRNA Electroporation to Modulate Autophagy in Herpes Simplex Virus Type 1-Infected Monocyte-Derived Dendritic Cells
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LDHA-lactate axis modulates mitophagy inhibiting CSFV replication.

Sen Zeng1,2, Zipeng Luo2, Wenhui Zhu2

  • 1College of Animal Science & Technology, Zhongkai University of Agriculture and Engineering, Guangzhou, China.

Journal of Virology
|April 23, 2025
PubMed
Summary

Classical swine fever virus (CSFV) infection boosts lactate dehydrogenase A (LDHA) and lactate production. Lactate then inhibits mitophagy and suppresses CSFV replication by activating the JAK-STAT pathway.

Keywords:
CSFVJAK-STATLDHAlactatemitophagy

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Area of Science:

  • Cellular Biology
  • Virology
  • Immunology

Background:

  • Lactate dehydrogenase A (LDHA) regulates lactate synthesis, a key glycometabolism byproduct with roles in metabolism and immunity.
  • Classical swine fever virus (CSFV) infection disrupts host glycometabolism, increasing lactate levels.
  • The interplay between CSFV and the LDHA-lactate axis was previously unclear.

Purpose of the Study:

  • To investigate the mutual regulation between CSFV and the LDHA-lactate axis.
  • To elucidate the role of LDHA and lactate in CSFV infection and host cellular processes.
  • To explore potential antiviral strategies targeting cellular metabolism.

Main Methods:

  • In vivo and in vitro experiments to assess LDHA expression and lactate production during CSFV infection.
  • Western blot, laser confocal microscopy, and transmission electron microscopy to analyze mitophagy.
  • Investigation of the JAK1-STAT1-ISG15 signaling pathway.

Main Results:

  • CSFV infection increases LDHA expression, potentially due to attenuated ISGylation.
  • CSFV induces L-lactate production dependent on LDHA.
  • LDHA and exogenous lactate inhibit PINK1-Parkin-mediated mitophagy.
  • Lactate activates the JAK1-STAT1-ISG15 network, suppressing CSFV replication.

Conclusions:

  • The LDHA-lactate axis plays a significant role in regulating mitophagy and the JAK-STAT pathway during CSFV infection.
  • Lactate acts as a signaling molecule that antagonizes CSFV replication.
  • This study reveals novel mechanisms of viral-host interaction and offers insights for antiviral development.