Axin expression delays herpes simplex virus-induced autophagy and enhances viral replication in L929 cells

Authors

  • Eun-Jin Choi,

    1. Laboratory of Cell Biology, Department of Microbiology and Bank for Pathogenic Virus, College of Medicine, Korea University, Seoul, Korea
    Search for more papers by this author
  • Sun-Ho Kee

    Corresponding author
    1. Laboratory of Cell Biology, Department of Microbiology and Bank for Pathogenic Virus, College of Medicine, Korea University, Seoul, Korea
    • Correspondence

      Sun-Ho Kee, Laboratory of Cell Biology, Department of Microbiology and Bank for Pathogenic Virus, College of Medicine, Korea University, Seoul, 136-705, Korea.

      Tel: +82 2 920 6165; fax: +82 2 923 3645; email: keesh@korea.ac.kr

    Search for more papers by this author

ABSTRACT

Axin, a negative regulator of the Wnt signaling pathway, plays a critical role in various cellular events including cell proliferation and cell death. Axin-regulated cell death affects multiple processes, including viral replication. For example, axin expression suppresses herpes simplex virus (HSV)-induced necrotic cell death and enhances viral replication. Based on these observations, this study investigated the involvement of autophagy in regulation of HSV replication and found axin expression inhibits autophagy-mediated suppression of viral replication in L929 cells. HSV infection induced autophagy in a time- and viral dose-dependent manner in control L929 cells (L-EV), whereas virus-induced autophagy was delayed in axin-expressing L929 cells (L-axin). Subsequent analysis showed that induction of autophagy by rapamycin reduced HSV replication, and that inhibiting autophagy by 3-methyladenine (3MA) and beclin-1 knockdown facilitated viral replication in L-EV cells. In addition, preventing autophagy with 3MA suppressed virus-induced cytotoxicity in L-EV cells. In contrast, HSV replication in L-axin cells was resistant to changes in autophagy. These results suggest that axin expression may render L929 cells resistant to HSV-infection induced autophagy, leading to enhanced viral replication.

Ancillary