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Institute of Virology

Philipp Kolb & Team


Research Topics

Fc-gamma receptors and their role in congenital HCMV infection

Human cytomegalovirus (HCMV) is one of the nine known human herpesviruses. It causes a particularly high disease burden in congenitally infected newborns, often leading to severe physical or sensorineural defects. There is no vaccine available and antiviral therapy against HCMV disease is restricted to few antiviral agents fraught with severe side effects including teratogenic damage and emergence of virus resistance. Consequentially, they are not applicable in some clinical settings including pregnancy. Therefore, vulnerable patient groups will greatly benefit from alternative intervention strategies with fewer risks by specifically targeting determinants of congenital infection.

We found that targeting a set of antibody binding glycoproteins encoded by HCMV (vFcγRs gp34 and gp68) is a promising new strategy to achieve this. We previously published how vFcγRs block antibody effector functions such as ADCC by NK cells. We are now working on a new model in which these molecules also enhance transmission of HCMV particles across the syncytiotrophoblast barrier separating mother and foetus. We hypothesize that HCMV achieves this by utilizing its vFcγRs arsenal to exploit the neonatal Fc receptor (FcRn), which is usually tasked with the transport of antibodies across the placental trophoblast via transcytosis.

Selected Publications

  • Chen H, Maul-Pavicic A, Holzer M, Salzer U, Chevalier N,  Voll RE, Hengel H & Kolb P. FcγR responses to soluble immune complexes of varying size: A scalable cell-based reporter system. 2020 - BioRxiv doi:10.1101/2020.11.11.378232
  • Kolb P, Hoffmann K, Sievert A, Reinhard H, Mercé-Maldonado E,  Le-Trilling VTK, Gütle D, Hengel H. Human Cytomegalovirus antagonizes activation of Fcγ receptors II and III by distinct and synergizing modes of IgG manipulation. 2020 - BioRxiv doi:10.1101/2020.10.12.335539
  • Pérez-Portilla A, Moraru M, Blázquez-Moreno A, Kolb P, Bravo García-Morato M, Ranganath T, Esteso G, Gianelli C, Rodríguez-Pena R, Lozano-Rodríguez R, Torres-Canizales JM, Blish CA, Vales-Gomez M, Hengel H, Vilches C, López-Granados E, Reyburn HT. Identification of the first cases of complete CD16A deficiency: Association with persistent EBV infection. 2020 - JACI. doi:10.1016/j.jaci.2019.11.049
  • Kolb P, Sijmons S, McArdle MR, Taher H, Womack J, Hughes C, Ventura A, Jarvis MA, Stahl-Hennig C, Hansen S, Picker LJ, Malouli D, Hengel H, Früh K.. Identification and functional characterization of a novel Fc gamma-binding glycoprotein in rhesus cytomegalovirus. 2019 - J Virol doi:10.1128/JVI.02077-18

 

Funded projects

EQUIP – Medical Scientist Programme 2020/2021

https://www.med.uni-freiburg.de/de/forschung/karrierewege/medical-scientist

 

Participation in research consortia (PI: Hartmut Hengel)

DFG-Forschergruppe 2830 „Advanced Concepts in Cellular Immune Control of Cytomegalovirus“

NIH CMV P01 "Immunologic and Virologic Determinants of Congenital Cytomegalovirus Transmission and Disease in Rhesus Monkeys”, Grant Number: 1P01AI129859-01A1

Infect-ERA: TANKACY (TArgeting Natural Killer cells Against CYtomegalovirus) - concluded

Kompetenznetzwerk Zytomegalie Baden-Württemberg Ulm-Tübingen-Freiburg – concluded

 

 

Lab members & contact

Team Leader: Philipp Kolb (Ph.D.)
Phone: +49 761 203 6611
 

  • Sophia Petkova                MD thesis (since 11/2020)          
  • Ann-Kathrin Kohl             B.Sc thesis (since 09/2020)       
  • Magdalena Huber           M.Sc thesis (2019)                       
  • Haizhang Chen                MD thesis (2018)                           
  • Annika Sievert                  B.Sc thesis (2017)                         

Head

Prof. Dr. med. Hartmut Hengel
hartmut.hengel@uniklinik-freiburg.de

Team Leader:

Philipp Kolb
(Ph.D.)
Phone: +49 761 203 6611