title: Axin expression delays herpes simplex virus-induced autophagy and enhances viral replication in L929 cells.
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.
authors: Laboratory of Cell Biology, Department of Microbiology and Bank for Pathogenic Virus, College of Medicine, Korea University, Seoul, 136-705, Korea.
authors: Eun-Jin
authors: EJ
authors: Choi
authors: Sun-Ho
authors: SH
authors: Kee
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives / Q000494:pharmacology; D051017:Apoptosis Regulatory Proteins / Q000235:genetics; D001343:Autophagy / Q000187:drug effects; D060466:Axin Protein / Q000235:genetics / Q000378:metabolism*; D000071186:Beclin-1; D002460:Cell Line; D015870:Gene Expression; D055785:Gene Knockdown Techniques; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics; D018139:Simplexvirus / Q000187:drug effects / Q000502:physiology*; D020123:Sirolimus / Q000494:pharmacology; D014779:Virus Replication / Q000187:drug effects
chemical_list: D051017:Apoptosis Regulatory Proteins; D060466:Axin Protein; C491997:BECN1 protein, human; D000071186:Beclin-1; D008565:Membrane Proteins; C025946:3-methyladenine; D000225:Adenine; D020123:Sirolimus
keywords: autophagy; axin; herpes simplex virus