Control of herpes simplex virus type 1 specific replication and transmission mechanisms in human dendritic cells

• Applicant: Professor Dr. Alexander Steinkasserer
• Subject Area: Immunology
• Term: from 2018 to 2022
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 398064017

• Final Report Year: 2022

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
  
• (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
  
• (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
  
• (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
  
• (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
  
• (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