Control of herpes simplex virus type 1 specific replication and transmission mechanisms in human dendritic cells
Final Report Abstract
In summary, in our view project was a very successful leading to new and unexpected data, including the fact that autophagic degradation of lamins is essential for the nuclear egress of HSV-1 and that mDC hamper this process, by upregulating KIF1B and KIF2A molecules, and thereby inhibiting the generation of mature infectious viral particles. In addition, we found that HSV-1 derived L-particles modulate the phenotype and stimulatory function of mDCS. Furthermore, targeting IL-6 R expression by HSV-1 on mDCs has been identified as a new viral immune escape mechanism. Finally, we provide data showing that HSV-2 interferes with DC migration and therefore the induction of potent antiviral immune responses. Work regarding mechanisms related to CD83 degradation and the functional ligand studies are still ongoing.
Publications
- (2020). Herpes simplex virus type-1 propagation and single-step growth curves. Bio-Protocol 9(23):e3441
Grosche L, Döhner K, Düthorn A, Hickford-Martinez A, Steinkasserer A, Sodeik B
(See online at https://doi.org/10.21769/bioprotoc.3441) - (2019). Autophagic degradation of lamins facilitates the nuclear egress of Herpes Simplex Virus type-1. Journal Cell Biology, 218(2):508-523
Turan A, Grosche L, Krawczyk A, Mühl-Zürbes P, Draßner C, Düthorn A, Kummer M, Hasenberg M, Voortmann S, Jastrow H, Dörrie J, Schaft N, Kraner M, Döhner K, Sodeik B, Steinkasserer A, Heilingloh CS
(See online at https://doi.org/10.1083/jcb.201801151) - (2020). Herpes simplex virus type-2 paralyzes dendritic cell function. Viruses 2020,12, 112
Grosche L, Mühl-Zürbes P, Ciblis B, Krawczyk A, Kuhnt C, Kamm L, Steinkasserer A, Heilingloh CS
(See online at https://doi.org/10.3390/v12010112) - (2020). HSV-1 modulates IL-6 receptor expression by human dendritic cells. Front Immunol.; 11:721
Birzer A, Krawczyk A, Draßner C, Kuhnt C, Mühl-Zürbes P, Heilingloh CS, Steinkasserer A, Popella L
(See online at https://doi.org/10.3389/fimmu.2020.01970) - (2020). Mass spectrometric characterization of HSV-1 L-particles from human dendritic cells and BHK21 cells and analyses of their functional role. Front. Microbiol. 2020 Sep 29; 11:1997
Birzer A, Kraner ME, Heilingloh CS, Mühl-Zürbes P, Hofmann J, Steinkasserer A, Popella L
(See online at https://doi.org/10.3389/fmicb.2020.01997) - (2020). The CD83 molecule – an important immune checkpoint. Front Immunol.
Grosche L, Knippertz I, Koenig K, Royzman D, Wild AB, Zinser E, Sticht H, Muller YA, Steinkasserer A, Lechmann M
(See online at https://doi.org/10.3389/fimmu.2020.00721)