Non-Structural Protein V of Canine Distemper Virus Induces Autophagy via PI3K/AKT/mTOR Pathway to Facilitate Viral Replication

Int J Mol Sci. 2024 Dec 25;26(1):84. doi: 10.3390/ijms26010084.

Abstract

Canine distemper (CD) is a highly infectious disease of dogs which is caused by canine distemper virus (CDV). Previous studies have demonstrated that CDV infection can induce autophagy in cells. However, the mechanism underlying CDV-induced autophagy remains not fully understood. The CDV non-structural protein V plays a vital role in viral replication and pathogenicity in the host. In this study, we investigated the relationship between the CDV-V protein and autophagy induction and further explored its impact on the viral replication and the mechanism behind this. Our results showed that the V protein induced autophagy via inhibiting the phosphorylation of PI3K, AKT, and mTOR to promote viral replication. The activation or inhibition of PI3K phosphorylation resulted in enhancing or reducing viral replication, respectively. Further studies revealed that the V protein interacted with PI3K to induce cellular autophagy. The present study demonstrated that the CDV-V protein can induce cellular autophagy by inhibiting the PI3K/AKT signaling pathway to enhance viral replication. The results improve the understanding of the molecular mechanism of CDV infection and offer new perspectives for the development of effective treatment and prevention strategies.

Keywords: CDV-V; PI3K; autophagy; canine distemper virus (CDV).

MeSH terms

  • Animals
  • Autophagy*
  • Chlorocebus aethiops
  • Distemper / metabolism
  • Distemper / virology
  • Distemper Virus, Canine* / pathogenicity
  • Distemper Virus, Canine* / physiology
  • Dogs
  • Phosphatidylinositol 3-Kinases* / metabolism
  • Phosphorylation
  • Proto-Oncogene Proteins c-akt* / metabolism
  • Signal Transduction*
  • TOR Serine-Threonine Kinases* / metabolism
  • Viral Nonstructural Proteins* / metabolism
  • Virus Replication*

Substances

  • Proto-Oncogene Proteins c-akt
  • Phosphatidylinositol 3-Kinases
  • Viral Nonstructural Proteins
  • TOR Serine-Threonine Kinases