Two types of autophagy in pathogenesis and antigen presentation of Herpes Simplex Virus type 1
Final Report Abstract
The research proposal funded by the DFG contained four specific goals, all of them aimed at elucidating the molecular mechanism and function of a novel autophagic pathway that had first been described by the lab of Michel Desjardins. We termed this pathway nuclear envelope-derived autophagy or NEDA. This pathway occurs only in cells that are infected with Herpes Simplex Virus type 1 (HSV1). We found to our surprise that NEDA induction has little in common with the well studied macroautophagy. Rather, it might be linked to the ER stress machinery. Since NEDA occurs at late times of infection when HSV1 can inhibit macroautophagy, we hypothesize that NEDA can act as a backup for macroautophagy. Preliminary results indicate that NEDA might indeed fulfill similar functions like the macroautophagic pathway in antiviral immunity, particularly concerning antigen presentation on MHC class I, and thus the activation of antiviral T cells.
Publications
- (2011). Alternative pathways for MHC class I presentation: a new function for Autophagy. Cellular & Molecular Life Sciences. 68: 1533 – 1541
Chemali M, Radtke K, Desjardins M & English L
- (2013). Inhibition of the Host Translation Shut-off Response by Herpes Simplex Virus 1 triggers Nuclear Envelope-Derived Autophagy. J Virol. 87: 3990-7
Radtke K, English L, Rondeau C, Leib D, Lippé R & Desjardins M
- (2013). Proteomics analysis of Herpes Simplex Virus type 1–infected cells reveals dynamic changes in viral protein expression, ubiquitylation and phosphorylation. Journal of Proteome Research 12: 1820-9
Bell C, Thibault P, Desjardins M & Radtke K
