The role of autophagy during coxsackievirus infection of neural progenitor and stem cells

• Published in: Autophagy Vol. 8; no. 6; pp. 938 - 953
• Main Authors: Tabor-Godwin, Jenna M., Tsueng, Ginger, Sayen, M. Richard, Gottlieb, Roberta A., Feuer, Ralph
• Format: Journal Article
• Language: English
• Published: United States Taylor & Francis 01.06.2012; Landes Bioscience
• Subjects: Adenine - analogs & derivatives; Adenine - pharmacology; Adenosine - analogs & derivatives; Adenosine - pharmacology; Animals; autophagy; Autophagy - drug effects; Basic Research Paper; Binding; Biology; Bioscience; Calcium; Cancer; Cell; Cell Differentiation - drug effects; central nervous system; coxsackievirus; Coxsackievirus Infections - pathology; Cycle; encephalitis; enterovirus; Enterovirus B, Human - drug effects; Enterovirus B, Human - physiology; Fibroblast Growth Factors - pharmacology; Green Fluorescent Proteins - metabolism; HeLa Cells; Humans; Landes; meningitis; Mice; Mice, Inbred C57BL; Microtubule-Associated Proteins - metabolism; neural stem cells; Neural Stem Cells - drug effects; Neural Stem Cells - metabolism; Neural Stem Cells - pathology; Neural Stem Cells - virology; neurotropic virus; Organogenesis; Proteins; Proto-Oncogene Proteins c-bcl-2 - metabolism; Signal Transduction - drug effects; Sirolimus - pharmacology; Transduction, Genetic; Viral Load - drug effects; Viral Proteins - metabolism; Virus Replication - drug effects
• ISSN: 1554-8627; 1554-8635
• DOI: 10.4161/auto.19781

Coxsackievirus B3 (CVB3) has previously been shown to utilize autophagy in an advantageous manner during the course of infection of the host cell. However, few studies have determined whether stem cells induce autophagy in a similar fashion, and whether virus-induced autophagy occurs following infection of stem cells. Therefore, we compared the induction of autophagy following CVB3 infection of neural progenitor and stem cells (NPSCs), which we have recently shown to be highly susceptible to CVB3 infection, to HL-1 cells, a transformed cardiomyocyte cell line. As previously demonstrated for other susceptible host cells, HL-1 cells showed an increase in the activity of autophagic signaling following infection with a CVB3 expressing dsRed protein (dsRed-CVB3). Furthermore, viral titers in HL-1 cells increased in the presence of an inducer of autophagy (CCPA), while viral titers decreased in the presence of an inhibitor of autophagy (3-MA). In contrast, no change in autophagic signaling was seen in NPSCs following infection with dsRed-CVB3. Also, basal levels of autophagy in NPSCs were found to be highly elevated in comparison to HL-1 cells. Autophagy could be induced in NPSCs in the presence of rapamycin without altering levels of dsRed-CVB3 replication. In differentiated NPSC precursors, autophagy was activated during the differentiation process, and a decrease in autophagic signaling was observed within all three CNS lineages following dsRed-CVB3 infection. Hence, we conclude that the role of autophagy in modulating CVB3 replication appears cell type-specific, and stem cells may uniquely regulate autophagy in response to infection.