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An autophagy-independent role for LC3 in equine arteritis virus replication

Iryna Monastyrska1, Mustafa Ulasli, Peter J M Rottier

  • 1Virology Division, Department of Infectious Diseases & Immunology, Utrecht University, Utrecht, The Netherlands.

Autophagy
|November 28, 2012
PubMed

Insights

Equine arteritis virus (EAV) uses modified cell membranes for replication. Researchers found microtubule-associated protein 1 light chain 3 (LC3) is crucial for EAV replication, independent of autophagy.

Area of Science:

  • Virology
  • Molecular Biology
  • Cell Biology

Background:

  • Equine arteritis virus (EAV), an enveloped positive-strand RNA virus, replicates within modified intracellular membranes forming double-membrane vesicles (DMVs).
  • The precise mechanisms and host factors involved in EAV-induced membrane modification and viral replication are not fully understood.

Purpose of the Study:

  • To investigate the role of autophagy-related proteins, specifically microtubule-associated protein 1 light chain 3 (LC3), in the replication of Equine arteritis virus (EAV).
  • To elucidate the function of EAV-induced double-membrane vesicles (DMVs) and their association with host cell machinery.

Main Methods:

  • Immuno-electron microscopy was used to visualize DMVs and associated proteins in EAV-infected cells.
  • Experiments were conducted in wild-type and autophagy-deficient cells (lacking ATG7) to assess the impact of autophagy on EAV replication.
  • LC3 depletion and re-expression studies were performed to determine its specific role in viral replication.

Main Results:

  • EAV-induced DMVs were found to contain double-stranded RNA and were decorated with LC3, even in autophagy-deficient cells.
  • Autophagy-related protein 7 (ATG7) deficiency did not impair EAV replication, suggesting autophagy is not essential.
  • Depletion of LC3 significantly reduced EAV replication, which could be rescued by expressing a nonlipidated form of LC3, indicating an autophagy-independent function.

Conclusions:

  • Microtubule-associated protein 1 light chain 3 (LC3) plays a critical, autophagy-independent role in Equine arteritis virus (EAV) replication.
  • EAV appears to hijack ER-derived membranes, specifically EDEMosomes (positive for EDEM1), for efficient replication, similar to other viruses.
  • These findings reveal a novel mechanism of viral replication involving host membrane manipulation and specific protein interactions.
Keywords:
LC3arterivirusautophagydouble-membrane vesiclesnidoviruses

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