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Research group/lab  |  Georges M.G.M. Verjans, MSc PhD

HerpeslabNL

The aim of the Herpesvirus Lab is to elucidate the virus-host interactions involved in the immune control and pathogenesis of herpesvirus infections in humans

About our research group/lab

Research

The HerpeslabNL aims to elucidate the virus and host factors involved in the immune control and pathogenesis of primate herpesviruses in their natural host: herpes simplex virus type 1 (HSV-1), Epstein-Barr virus (EBV), varicella zoster virus (VZV) and its primate counterpart simian varicella virus (SVV) in monkeys.

A hallmark of herpesviruses is their ability to establish a lifelong latent infection of sensory neurons (HSV-1, VZV and SVV) and B-cells (EBV) after primary infection. Reactivation of latent virus, which occasionally leads to recrudescent disease, is controlled by innate and adaptive immunity. Virus-specific immune responses are commonly beneficial (control of latent HSV-1, VZV and SVV in sensory neurons), but can also cause detrimental disease affecting the eye (uveitis and keratitis; HSV-1 and VZV) or brain: encephalitis (HSV-1 and VZV) or potentially Alzheimer’s disease (HSV-1) and multiple sclerosis (EBV). The lab has developed a unique infrastructure to acquire clinical specimens and state-of-the-art methodologies to characterize the virus status (genome, proteome and transcriptome), the virus’ cell tropism and the innate and adaptive cell types, their antigen-specificity and effector functions in (non-) human tissue specimens to identify the key factors that determine the clinical outcome of herpesvirus infections.

The ultimate goal of our research is to develop novel intervention strategies aimed to prevent reactivation and herpesvirus-induced pathogenesis.

Team, alumni, and dissertations

Current team:

   

Photo Seyar Rashidi









Ahmad Seyar Rashidi
Graduate student
Email: a.rashidi@erasmusmc.nl

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Diana N. Tran
Graduate student
Email d.tran@erasmusmc.nl

 

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Shirley E. Braspenning

Graduate student
Email: s.braspenning@erasmusmc.nl
ORCID ID

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Tamana Khemai-Mehraban

Technician
Email: t.mehraban@erasmusmc.nl

Photo Fatiha Zaaraoui Boutahar









Fatiha Zaaraoui-Boutahar
Technician
Email: f.zaaraoui@erasmusmc.nl

 

Photo Michiel van Gent









Michiel van Gent
Post-doctoral fellow
Email: m.vangent@erasmusmc.nl
ORCID ID
Photo Maaike









Maaike Moelker-Hang
Project Manager - Grant Advisor
Email: m.moelker@erasmusmc.nl

 Photo Werner Ouwendijk









Werner J.D. Ouwendijk
Assistant professor
Email: w.ouwendijk@erasmusmc.nl
ORCID ID
Link to thesis W.J.D. Ouwendijk (2013)

Photo Georges Verjans









Georges M.G.M. Verjans
Associate professor (PI)
Email: g.verjans@erasmusmc.nl
ORCID ID



Alumni:

Post-doctoral fellows
 Current position
 
Peter-Paul Unger
 
2019 – 2021
 
Scientist at Thermo Fisher Scientific (Leiden, Netherlands)
 
 
Eveline D. de Geus
 
2014 – 2015
 
Post-doc at Hudson Institute of Medical Research (Melbourne, Australia)
 

 

Graduate students  Current position
Gijs P. van Nierop
2010 – 2018

Post-doc at Erasmus MC (Rotterdam, Netherlands) 
Link to thesis G.P. van Nierop (2018)
 
Erik Schaftenaar
2012 – 2016 

Microbiologist at St. Antonius hospital (Utrecht, Netherlands)
Link to thesis E. Schaftenaar (2016)
 
Monique van Velzen
2008 – 2013

Assistant professor at LUMC (Leiden, Netherlands)
Link to thesis M. van Velzen (2013)
 
Rui Duan
2004 – 2009


Scientist at Kite Pharma (Den Haag, Netherlands)
Link to thesis R. Duan (2009)
 

Jeroen Maertzdorf
1998 – 2002

Max Planck Institute for Infection Biology (Berlin, Germany)
Link to thesis J. Maertzdorf (2002)
 
Lies Remeijer
1997 – 2002

Chief ophthalmologist (Rotterdam, Netherlands)
Link to thesis L. Remeijer (2002)
 

 

Projects

 

Large Scale T Cell Epitope Discovery: Local and Systemic T-cell Response to Herpes Simplex Virus
Project Aims:
To characterize the phenotype, functional characteristics and fine antigen specificity of virus-specific T-cells in HSV-1 infected human corneas and trigeminal ganglia.
Team: Michiel van Gent & Georges M.G.M. Verjans
International collaboration: David M. Koelle (University of Washington, Seattle WA)
Funding: National Institute of Allergy and Infectious Diseases (75N93019C00063-0-9999-1)


Role of VZV latency transcript (VLT) and ORF63 in latency and reactivation

Project Aims: To determine the role of VLT and ORF63 in latency establishment/ maintenance/ reactivation in human neurons ex vivo, in situ and in vitro.
Team: Shirley E. Braspenning, Werner J.D. Ouwendijk & Georges M.G.M. Verjans
International collaboration: Paul (Kip) R. Kinchington (University of Pittsburgh, Pittsburgh, PA)
Funding: National Institute of Allergy and Infectious Diseases (R01-AI151290-01A1)


Cutaneous Pathogen-Specific Tissue Resident Memory T Cells in Human Aging

Project Aims: To determine the role of HSV-1 reactive T-cells in the pathophysiology of Alzheimer’s disease.
Team: Michiel van Gent, Peter-Paul Unger & Georges M.G.M. Verjans
International collaboration: David M. Koelle (University of Washington, Seattle WA)
Funding: National Institute of Aging (R01-AG064800-02S1)


Human organotypic brain slice model: a novel platform to study virus-induced neuropathology

Project Aims: To determine the virus tropism and pathogenesis of neurotropic viruses using the human ex-vivo brain slice culture platform to be developed.
Team: Diana N. Tran & Georges M.G.M. Verjans
International collaboration: not applicable
Funding: Erasmus MC: Human Disease Model Award


Single cell analysis of T-cell receptors and transcriptome in tissue of multiple sclerosis patients

Project Aims: To determine the fine antigen specificity, function and spatial orientation of dominant CD8 T-cells in brain lesions of multiple sclerosis patients.
Team: Peter-Paul Unger & Georges M.G.M. Verjans
International collaboration: Stephen J. Elledge (Harvard Medical School, Boston MA) & Roland Martin (University of Zurich, Zurich, Switzerland)
Funding: Dutch MS Research Foundation (17-995 MS)


Cell death in the central nervous system: mechanisms and impact on disease pathogenesis.

Project Aims: To identify the types of cell death that occur in diseases in the CNS, identify the molecular mechanisms involved, and decipher the impact on pathology.
Team: Ahmad Seyar Rashidi & Georges M.G.M. Verjans
International collaboration: Søren R. Paludan (Aarhus University Aarhus, Denmark)
Funding: Lundbeckfonden (R276-2018-192)


Publications

 

 
2022


Microglia activate early anti-viral responses upon HSV-1 entry into the brain to counteract development of encephalitis-like disease in mice.

Katzilieris-Petras G, Lai X, Rashidi AS, Verjans GM, Reinert LS & Paludan SR. J Virol. 2022 Jan 19: doi: 10.1128/JVI.01311-21.
 

2021

No evidence of aberrant amyloid β and phosphorylated tau expression in herpes simplex virus-infected neurons of the trigeminal ganglia and brain.
Tran DN, Bakx AT, van Dis V, Aronica E, Verdijk RM & Ouwendijk WJ. Brain Pathol. 2021 Dec 16. doi: 10.1111/bpa.13044.


Mutagenesis of the varicella-zoster virus genome demonstrates that VLT and VLT-ORF63 proteins are dispensable for lytic infection.
Braspenning SE, Lebbink RJ, Depledge DP, Schapendonk CME, Anderson LA, Verjans GM, Sadaoka T** & Ouwendijk WJ**. Viruses. 2021 Nov 16. doi: 10.3390/v13112289.


The architecture of the simian varicella virus transcriptome.
Braspenning SE, Verjans GM, Mehraban T, Messaoudi I, Depledge DP** & Ouwendijk WJ**. PLoS Pathog. 2021 Nov 22. doi: 10.1371/journal.ppat.1010084.


Generation of hiPSC-derived low threshold mechanoreceptors containing axonal termini resembling bulbous sensory nerve endings and expressing Piezo1 and Piezo2.
Zhu S, Stanslowsky N, Fernández-Trillo J, Mamo TM, Yu P, Kalmbach N, Ritter B, Eggenschwiler R, Ouwendijk WJ, Mzinza D, Tan L, Leffler A, Spohn M, Brown RJP, Kropp KA, Kaever V, Ha TC, Narayanan P, Grundhoff A, Förster R, Schambach A, Verjans GM, Schmidt M, Kispert A, Cantz T, Gomis A, Wegner F & Viejo-Borbolla A. Stem Cell Res. 2021 Oct 21. doi: 10.1016/j.scr.2021.102535.


Local immune control of latent herpes simplex virus type 1 in ganglia of mice and man.
St Leger AJ, Koelle DM, Kinchington PR & Verjans GM. Front Immunol. 2021 Sep 15. doi: 10.3389/fimmu.2021.723809


Cluster of symptomatic graft-to-host transmission of herpes simplex virus type 1 in an endothelial keratoplasty setting.
Guerra-Assunção JA*, van Kampen JJ*, Roy S, Remeijer L, Breuer J & Verjans GM. Ophthalmol Science. 2021 Aug 11. DOI: 10.1016/j.xops.2021.100051


Comparable infection level and tropism of measles virus and canine distemper virus in organotypic brain slice cultures obtained from natural host species.
Laksono BM*, Tran DN*, Kondova I, van Engelen HGH, Michels S, Nambulli S, de Vries RD, Duprex WP, Verjans GM & de Swart RL. Viruses. 2021 Aug 10. doi: 10.3390/v13081582.


High levels of neutrophil extracellular traps persist in the lower respiratory tract of critically ill patients with coronavirus disease.
Ouwendijk WJ, Raadsen MP, van Kampen JJ, Verdijk RM, von der Thusen JH, Guo L, Hoek RA, van den Akker JP, Endeman H, Langerak T, Molenkamp R, Gommers D, Koopmans MP, van Gorp EC, Verjans GM & Haagmans BL. J Infect Dis. 2021 May 20. doi: 10.1093/infdis/jiab050.

Varicella-zoster virus VLT-ORF63 fusion transcript induces broad viral gene expression during reactivation from neuronal latency.
Ouwendijk WJ*, Depledge DP*, Rajbhandari L, Lenac Rovis T, Jonjic S, Breuer J, Venkatesan A, Verjans GM & Sadaoka T. Nat Commun. 2020 Dec 10. doi: 10.1038/s41467-020-20031-4.


An organoid-derived bronchioalveolar model for SARS-CoV-2 infection of human alveolar type II-like cells.
Lamers MM, van der Vaart J, Knoops K, Riesebosch S, Breugem TI, Mykytyn AZ, Beumer J, Schipper D, Bezstarosti K, Koopman CD, Groen N, Ravelli RBG, Duimel HQ, Demmers JA, Verjans GM, Koopmans MP, Muraro MJ, Peters PJ, Clevers H & Haagmans BL. EMBO J. 2021 Mar 1. doi: 10.15252/embj.2020105912.

2020

Decoding the architecture of the varicella-zoster virus transcriptome.
Braspenning SE, Sadaoka T, Breuer J, Verjans GM, Ouwendijk WJ** & Depledge DP**. mBio. 2020 Oct 6. doi: 10.1128/mBio.01568-20.


Alveolar barrier disruption in varicella pneumonia is associated with neutrophil extracellular trap formation.
Ouwendijk WJ, van den Ham HJ, Delany MW, van Kampen JJ, van Nierop GP, Mehraban T, Zaaraoui-Boutahar F, van IJcken WF, van den Brand JM, de Vries RD, Andeweg AC & Verjans GM. JCI Insight. 2020 Nov 5. doi: 10.1172/jci.insight.138900.


Brain immune cells undergo cGAS/STING-dependent apoptosis during herpes simplex virus type 1 infection to limit type I IFN production.
Reinert LS, Rashidi AS*, Tran DN*, Katzilieris-Petras G, Hvidt AK, Gohr M, Fruhwürth S, Bodda C, Thomsen MK, Vendelbo MH, Khan AR, Hansen B, Bergström P, Agholme L, Mogensen TH, Christensen MH, Nyengaard JR, Sen GC, Zetterberg H, Verjans GM & Paludan SR. J Clin Invest. 2021 Jan 4. doi: 10.1172/JCI136824.

No evidence of varicella-zoster virus infection in temporal artery biopsies of anterior ischemic optic neuropathy patients with and without giant cell arteritis.
Verdijk RM, Ouwendijk WJ, Kuijpers RW & Verjans GM. J Infect Dis. 2021 Jan 4. doi: 10.1093/infdis/jiaa566.


Analysis of virus and host proteomes during productive HSV-1 and VZV infection in human epithelial cells.
Ouwendijk WJ, Dekker LJ, van den Ham HJ, Lenac Rovis T, Haefner ES, Jonjic S, Haas J, Luider TM & Verjans GM. Front Microbiol. 2020 May 29. doi: 10.3389/fmicb.2020.01179.


Ileocolic intussusception as the presenting symptom of primary enteric varicella-zoster virus infection in a 7-month-old infant.
Windster JD, Ouwendijk WJ, Sloots CEJ, Verjans GM & Verdijk RM. J Infect Dis. 2020 Jun 29. doi: 10.1093/infdis/jiaa148.


Large, stable, contemporary interspecies recombination events in circulating human herpes simplex viruses.
Casto AM, Roychoudhury P, Xie H, Selke S, Perchetti GA, Wofford H, Huang ML, Verjans GM, Gottlieb GS, Wald A, Jerome KR, Koelle DM, Johnston C & Greninger AL. J Infect Dis. 2020 Mar 28. doi: 10.1093/infdis/jiz199.

2018

Immunobiology of varicella-zoster virus infection.
Laing KJ, Ouwendijk WJ, Koelle DM & Verjans GM. J Infect Dis. 2018 Sep 22. doi: 10.1093/infdis/jiy403.


Simian varicella virus infects enteric neurons and α4β7 integrin-expressing gut-tropic T-cells in nonhuman primates.
Ouwendijk WJ, van Veen S, Mehraban T, Mahalingam R & Verjans GM. Viruses. 2018 Mar 28. doi: 10.3390/v10040156.


A spliced latency-associated VZV transcript maps antisense to the viral transactivator gene 61.
Depledge DP*, Ouwendijk WJ*, Sadaoka T*, Braspenning SE, Mori Y, Cohrs RJ, Verjans GM** & Breuer J**. Nat Commun. 2018 Mar 21. doi: 10.1038/s41467-018-03569-2.


Immunopathology of virus-induced anterior uveitis.
De Groot-Mijnes JDF, Chan ASY, Chee SP & Verjans GM. Ocul Immunol Inflamm. 2018 Mar 15. doi: 10.1080/09273948.2018.1439069.


Molecular aspects of varicella-zoster virus latency.
Depledge DP, Sadaoka T & Ouwendijk WJ. Viruses. 2018 Jun 28. doi: 10.3390/v10070349.


Attenuation of simian varicella virus infection by enhanced green fluorescent protein in rhesus macaques.
Mahalingam R, Kaufer BB, Ouwendijk WJ, Verjans GM, Coleman C, Hunter M, Das A, Palmer BE, Clambey E, Nagel MA, Traina-Dorge V. J Virol. 2018 Mar 14. doi: 10.1128/JVI.02253-17

2017

Elevated EBNA-1 IgG in MS is associated with genetic ms risk variants.
Kreft KL, Van Nierop GP, Scherbeijn SMJ, Janssen M, Verjans GM & Hintzen RQ. Neurol Neuroimmunol Neuroinflamm. 2017 Oct 12. doi: 10.1212/NXI.0000000000000406.


Antibody-based immunotherapy of aciclovir resistant ocular herpes simplex virus infections.
Bauer D, Keller J, Alt M, Schubert A, Aufderhorst UW, Palapys V, Kasper M, Heilingloh CS, Dittmer U, Laffer B, Eis-Hübinger AM, Verjans GM, Heiligenhaus A, Roggendorf M & Krawczyk A. Virology. 2017 Oct 3. doi: 10.1016/j.virol.2017.09.021.


Simian varicella virus inhibits the interferon gamma signalling pathway.
Ouwendijk WJ, van Veen S, Mahalingam R & Verjans GM. J Gen Virol. 2017 Oct 10. doi: 10.1099/jgv.0.000925.


Phenotypic and functional characterization of T cells in white matter lesions of multiple sclerosis patients.
van Nierop GP, van Luijn MM, Michels SS, Melief MJ, Janssen M, Langerak AW, Ouwendijk WJ, Hintzen RQ & Verjans GM. Acta Neuropathol. 2017 Jun 17. doi: 10.1007/s00401-017-1744-4.


Varicella zoster virus glycoprotein C increases chemokine-mediated leukocyte migration.
González-Motos V, Jürgens C, Ritter B, Kropp KA, Durán V, Larsen O, Binz A, Ouwendijk WJ, Lenac Rovis T, Jonjic S, Verjans GM, Sodeik B, Krey T, Bauerfeind R, Schulz TF, Kaufer BB, Kalinke U, Proudfoot AE, Rosenkilde MM & Viejo-Borbolla A. PLoS Pathog. 2017 May 25. doi: 10.1371/journal.ppat.1006346.


Satellite glial cells in human trigeminal ganglia have a broad expression of functional Toll-like receptors.
Mitterreiter JG, Ouwendijk WJ, van Velzen M, van Nierop GP, Osterhaus AD & Verjans GM. Eur J Immunol. 2017 Jun 1. doi: 10.1002/eji.201746989.


European consensus-based (S2k) Guideline on the Management of Herpes Zoster - guided by the European Dermatology Forum (EDF) in cooperation with the European Academy of Dermatology and Venereology (EADV), part 1: diagnosis.

Werner RN, Nikkels AF, Marinović B, Schäfer M, Czarnecka-Operacz M, Agius AM, Bata-Csörgő Z, Breuer J, Girolomoni G, Gross GE, Langan S, Lapid-Gortzak R, Lesser TH, Pleyer U, Sellner J, Verjans GM, Wutzler P, Dressler C, Erdmann R, Rosumeck S & Nast A. J Eur Acad Dermatol Venereol. 2017 Nov 2. doi: 10.1111/jdv.13995.


European consensus-based (S2k) Guideline on the Management of Herpes Zoster - guided by the European Dermatology Forum (EDF) in cooperation with the European Academy of Dermatology and Venereology (EADV), Part 2: Treatment.
Werner RN, Nikkels AF, Marinović B, Schäfer M, Czarnecka-Operacz M, Agius AM, Bata-Csörgő Z, Breuer J, Girolomoni G, Gross GE, Langan S, Lapid-Gortzak R, Lesser TH, Pleyer U, Sellner J, Verjans GM, Wutzler P, Dressler C, Erdmann R, Rosumeck S & Nast A. J Eur Acad Dermatol Venereol. 2017 Nov 2. doi: 10.1111/jdv.13957.

 

Collaborations

Collaborations within Erasmus MC

Collaborations outside of Erasmus MC

News

2022

Juli 2022

Minisymposium "Herpesviruses: molecular interactions between virus and host" 

Date: 24 october 2022
Location: Science Tower, Rotterdam and online
Time: 13:00 - 17:15 

Program Minisymposium Herpesviruses: molecular interactions between virus and host

REGISTER HERE 

 

Photo Graduation Mike EtermanMay 2022:
After performing an 8-month internship in the HerpesLab, Mike Eterman obtained his MSc degree in Biomedical Sciences at the Leiden University Medical Center. Dr. Werner Ouwendijk attended the graduation ceremony and awarded Mike his degree (image; Mike: left, Werner: right).


March 2022:
HerpesLab researcher Dr. Michiel van Gent is awarded a two-year Marie Curie Postdoctoral Fellowship (link).

 

 

Join us

Interested in joining us?



GENERAL POSITIONS:
We are always seeking talented and passionate scientists to join our team, from students to postdocs to staff scientists. If you are interested in joining us, please send an email to HerpeslabNL@erasmusmc.nl and include your CV and contact information for 2-3 references.



TARGETED POSITIONS:

Senior post-doctoral researcher
Human virus-specific tissue-resident T cells

Job description
A 2-year senior post-doctoral researcher position is available in our laboratory to study the role of virus-specific tissue-resident T cells (TRM) involved in the control vs. pathogenesis of herpes simplex virus type 1 (HSV-1) infections in humans. The project will involve detailed analysis of the phenotype, fine antigen specificity and spatial orientation of human HSV-1 reactive CD4 and CD8 TRM cells in trigeminal ganglia (immune control) and corneas (immunopathogenesis) of latently HSV-1-infected individuals.

For more information about this position, please contact Dr. Georges M. Verjans by email: g.verjans@erasmusmc.nl.