A Neuron-Specific Role for Autophagy in Antiviral Defense against Herpes Simplex Virus

SummaryType I interferons (IFNs) are considered to be the universal mechanism by which viral infections are controlled. However, many IFN-stimulated genes (ISGs) rely on antiviral pathways that are toxic to host cells, which may be detrimental in nonrenewable cell types, such as neurons. We show that dorsal root ganglionic (DRG) neurons produced little type I IFNs in response to infection with a neurotropic virus, herpes simplex type 1 (HSV-1). Further, type I IFN treatment failed to completely block HSV-1 replication or to induce IFN-primed cell death in neurons. We found that DRG neurons required autophagy to limit HSV-1 replication both in vivo and in vitro. In contrast, mucosal epithelial cells and other mitotic cells responded robustly to type I IFNs and did not require autophagy to control viral replication. These findings reveal a fundamental difference in the innate antiviral strategies employed by neurons and mitotic cells to control HSV-1 infection.

Graphical AbstractFigure optionsDownload full-size imageDownload high-quality image (227 K)Download as PowerPoint slideHighlights► Neurons produce less type I interferons (IFNs) than mitotic cells ► IFN-induced responses to herpes simplex virus type 1 (HSV-1) are reduced in neurons ► Type I IFN primes primary mitotic cells, but not neurons, for cell death ► Neurons, but not epithelial cells, require autophagy to control HSV-1 in vivo