Geisel School of Medicine
The cellular autophagy response induced by herpes simplex virus 1 (HSV-1) is countered by the viral γ34.5 protein. γ34.5 modulates autophagy by binding to the host autophagy protein Beclin-1 and through this binding inhibits the formation of autophagosomes in fibroblasts and neurons. In contrast, in this study dendritic cells (DCs) infected with HSV-1 showed an accumulation of autophagosomes and of the long-lived protein p62. No such accumulations were observed in DCs infected with a γ34.5-null virus or a virus lacking the Beclin-binding domain (BBD) of γ34.5. To explore this further, we established stably transduced DC lines to show that γ34.5 expression alone induced autophagosome accumulation yet prevented p62 degradation. In contrast, DCs expressing a BBD-deleted mutant of γ34.5 were unable to modulate autophagy. DCs expressing γ34.5 were less capable of stimulating T-cell activation and proliferation in response to intracellular antigens, demonstrating an immunological consequence of inhibiting autophagy. Taken together, these data show that in DCs, γ34.5 antagonizes the maturation of autophagosomes and T cell activation in a BBD-dependent manner, illustrating a unique interface between HSV and autophagy in antigen-presenting cells.
Gobeil PA, Leib DA. Herpes simplex virus γ34.5 interferes with autophagosome maturation and antigen presentation in dendritic cells. mBio. 2012 Oct 16;3(5):e00267-12. doi: 10.1128/mBio.00267-12. PMID: 23073763; PMCID: PMC3470650.
Dartmouth Digital Commons Citation
Gobeil, Philipe A. M. and Leib, David A., "Herpes Simplex Virus 34.5 Interferes with Autophagosome Maturation and Antigen Presentation in Dendritic Cells" (2012). Dartmouth Scholarship. 1561.