The HerpeslabNL aims to elucidate the virus and host factors involved in the immune control and pathogenesis of the human neurotropic herpes simplex viruses (HSV) and varicella zoster virus (VZV) in their natural host.

A hallmark of these herpesviruses is their ability to establish a lifelong latent infection after primary infection of neurons in sensory ganglia (HSV) or along the entire neuraxis (VZV). 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 infection in sensory neurons), but can also cause detrimental disease affecting the eye (uveitis and keratitis) or the brain (encephalitis and potentially Alzheimer’s disease). The HerpeslabNL has developed a unique infrastructure to acquire human clinical specimens in combination with 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 present at the site of infection including their antigen-specificity and effector functions. This enables the identification of the key host and virus factors that determine the clinical outcome of alpha-herpesvirus infections and disease.

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

Current team:

Georges M.G.M. Verjans Associate professor (PI) Email: g.verjans@erasmusmc.nl ORCID ID	Werner J.D. Ouwendijk Assistant professor Email: w.ouwendijk@erasmusmc.nl ORCID ID Link to thesis W.J.D. Ouwendijk (2013)
Michiel van Gent Assistant professor Email: m.vangent@erasmusmc.nl ORCID ID	Maaike Moelker-Hang Project Manager - Grant Advisor Email: m.moelker@erasmusmc.nl
José Afonso Guerra-Assunção Post-doc	Fatiha Zaaraoui-Boutahar Technician Email: f.zaaraoui@erasmusmc.nl
Tamana Khemai-Mehraba Technician Email: t.mehraban@erasmusmc.nl	Sem M. van ‘t Geloof  Technician Email: s.vantgeloof@erasmusmc.nl
Ahmad Seyar Rashidi Graduate student Email: a.rashidi@erasmusmc.nl	Diana N. Tran Graduate student Email d.tran@erasmusmc.nl
Mark Power  Graduate student Email: m.power@erasmusmc.nl	Lex Havelaar  Graduate student Email: a.havelaar@erasmusmc.nl
Anaïs M.T.Y. Wiech Graduate student Email: a.wiech@erasmusmc.nl	Teun van der Klugt Graduate student Email: t.klugt@erasmusmc.nl

Alumni

2024

• Marshall EM^*, Rashidi AS^*, van Gent M, Rockx B, Verjans GM. Neurovirulence of Usutu virus in human fetal organotypic brain slice cultures partially resembles Zika and West Nile virus. Sci Rep. 2024;14:20095. doi: 10.1038/s41598-024-71050-w.

• Zheng S, Verjans GM, Evers A, van den Wittenboer E, Tjhie JH, Snoeck R, Wiertz EJ, Andrei G, van Kampen JJ, Lebbink RJ. CRISPR/Cas9-mediated genome editing of the thymidine kinase gene in a clinical HSV-1 isolate identifies F289S as novel acyclovir-resistant mutation. Antiviral Res. 2024;228:105950. doi: 10.1016/j.antiviral.2024.105950.

• Heinz JL, Hinke DM, Maimaitili M, Wang J, Sabli IKD, Thomsen M, Farahani E, Ren F, Hu L, Zillinger T, Grahn A, von Hofsten J, Verjans GM, Paludan SR, Viejo-Borbolla A, Sancho-Shimizu V, Mogensen TH. Varicella zoster virus-induced autophagy in human neuronal and hematopoietic cells exerts antiviral activity. J Med Virol. 2024;96:e29690. doi: 10.1002/jmv.29690.

• Ouwendijk WJ, Roychoudhury P, Cunningham AL, Jerome KR, Koelle DM, Kinchington PR, Mohr I, Wilson AC, Verjans GM^*, Depledge DP^*. Reply to Wang et al., "Ample evidence for the presence of HSV-1 LAT in non-neuronal ganglionic cells of mice and humans". J Virol. 2024;98:e0052024. doi: 10.1128/jvi.00520-24.

• Rashidi AS^*, Tran DN^*, Peelen CR, van Gent M, Ouwendijk WJ, Verjans GM. Herpes simplex virus infection induces necroptosis of neurons and astrocytes in human fetal organotypic brain slice cultures. J Neuroinflammation. 2024;21:38. doi: 10.1186/s12974-024-03027-5.

  2023

• Heinz JL, Swagemakers SM, von Hofsten J, Helleberg M, Thomsen MM, De Keukeleere K, de Boer JH, Ilginis T, Verjans GM, van Hagen PM, van der Spek PJ, Mogensen TH. Whole exome sequencing of patients with varicella-zoster virus and herpes simplex virus induced acute retinal necrosis reveals rare disease- associated genetic variants. Front Mol Neurosci. 2023;16:1253040. doi: 10.3389/fnmol.2023.1253040.

• Hullegie-Peelen DM, Tejeda Mora H, Hesselink DA, Bindels EM, van den Bosch TP, Clahsen-van Groningen MC, Dieterich M, Heidt S, Minnee RC, Verjans GM, Hoogduijn MJ, Baan CC. Virus-specific TRM cells of both donor and recipient origin reside in human kidney transplants. JCI Insight. 2023;8:e172681. doi: 10.1172/jci.insight.172681.

• Ren F, Narita R, Rashidi AS, Fruhwürth S, Gao Z, Bak RO, Thomsen MK, Verjans GM, Reinert LS^*, Paludan SR^*. ER stress induces caspase-2-tBID-GSDME-dependent cell death in neurons lytically infected with herpes simplex virus type 2. EMBO J. 2023;42:e113118. doi: 10.15252/embj.2022113118.

• Malahe SR^*, van Kampen JJ^*, Manintveld OC, Hoek RA, den Hoed CM, Baan CC, Kho MM, Verjans GM. Current Perspectives on the Management of Herpesvirus Infections in Solid Organ Transplant Recipients. Viruses. 2023;15:1595. doi: 10.3390/v15071595.

• Ouwendijk WJ, Roychoudhury P, Cunningham AL, Jerome KR, Koelle DM, Kinchington PR, Mohr I, Wilson AC, Verjans GM^*, Depledge DP^*. Reanalysis of single-cell RNA sequencing data does not support herpes simplex virus 1 latency in non-neuronal ganglionic cells in mice. J Virol. 2024;98:e0185823. doi: 10.1128/jvi.01858-23.

• ·van Gent M, Ouwendijk WJ, Campbell VL, Laing KJ, Verjans GM^*, Koelle DM^*. Varicella-zoster virus proteome-wide T-cell screening demonstrates low prevalence of virus-specific CD8 T-cells in latently infected human trigeminal ganglia. J Neuroinflammation. 2023;20:141. doi: 10.1186/s12974-023-02820-y.

• Hoornweg TE, Godeke GJ, Hoogerwerf MN, van Kasteren PB, de Vries A, Sprong H, Verjans GM, van Riel D, Reimerink JH, Rockx B^*, Reusken CB^*. Rescue and in vitro characterization of a divergent TBEV-Eu strain from the Netherlands. Sci Rep. 2023;13:2872. doi: 10.1038/s41598-023-29075-0.

  2022

• Laing KJ, Ouwendijk WJ, Campbell VL, McClurkan CL, Mortazavi S, Elder Waters M, Krist MP, Tu R, Nguyen N, Basu K, Miao C, Schmid DS, Johnston C, Verjans GM, Koelle DM. Selective retention of virus-specific tissue-resident T cells in healed skin after recovery from herpes zoster. Nat Commun. 2022;13:6957. doi: 10.1038/s41467-022-34698-4.

• Unger PA, Oja AE, Khemai-Mehraban T, Ouwendijk WJ, Hombrink P, Verjans GM. T-cells in human trigeminal ganglia express canonical tissue-resident memory T-cell markers. J Neuroinflammation. 2022;19:249. doi: 10.1186/s12974-022-02611-x.

• Mulder EE, Damman J, Verver D, van der Veldt AA, Tas S, Khemai-Mehraban T, Heezen KC, Wouters RA, Verhoef C, Verjans GM, Langerak AW, Grünhagen DJ, Mooyaart AL. Histopathological and immunological spectrum in response evaluation of talimogene laherparepvec treatment and correlation with durable response in patients with cutaneous melanoma. Melanoma Res. 2022;32:249-259. doi: 10.1097/CMR.0000000000000824.

• Katzilieris-Petras G, Lai X, Rashidi AS, Verjans GM, Reinert LS^*, Paludan SR^*. Microglia Activate Early Antiviral Responses upon Herpes Simplex Virus 1 Entry into the Brain to Counteract Development of Encephalitis-Like Disease in Mice. J Virol. 2022;96:e0131121. doi: 10.1128/JVI.01311-21.

• Tran DN, Bakx AT, van Dis V, Aronica E, Verdijk RM, Ouwendijk WJ. No evidence of aberrant amyloid β and phosphorylated tau expression in herpes simplex virus-infected neurons of the trigeminal ganglia and brain. Brain Pathol. 2022;32:e13044. doi: 10.1111/bpa.13044.

  2021

• Braspenning SE, Lebbink RJ, Depledge DP, Schapendonk CM, Anderson LA, Verjans GM, Sadaoka T^*, Ouwendijk WJ^*. Mutagenesis of the Varicella-Zoster Virus Genome Demonstrates That VLT and VLT-ORF63 Proteins Are Dispensable for Lytic Infection. Viruses. 2021;13:2289. doi: 10.3390/v13112289.

• Braspenning SE, Verjans GM, Mehraban T, Messaoudi I, Depledge DP^*, Ouwendijk WJ^*. The architecture of the simian varicella virus transcriptome. PLoS Pathog. 2021;17:e1010084. doi: 10.1371/journal.ppat.1010084.

• 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 RJ, 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. Generation of hiPSC-derived low threshold mechanoreceptors containing axonal termini resembling bulbous sensory nerve endings and expressing Piezo1 and Piezo2. Stem Cell Res. 2021;56:102535. doi: 10.1016/j.scr.2021.102535.

• St Leger AJ, Koelle DM, Kinchington PR, Verjans GM. Local Immune Control of Latent Herpes Simplex Virus Type 1 in Ganglia of Mice and Man. Front Immunol. 2021;12:723809. doi: 10.3389/fimmu.2021.723809.

• Laksono BM^*, Tran DN^*, Kondova I, van Engelen HGH, Michels S, Nambulli S, de Vries RD, Duprex WP, Verjans GM, de Swart RL. Comparable Infection Level and Tropism of Measles Virus and Canine Distemper Virus in Organotypic Brain Slice Cultures Obtained from Natural Host Species. Viruses. 2021;13:1582. doi: 10.3390/v13081582.

• Guerra-Assunção JA^*, van Kampen JJ^*, Roy S, Remeijer L, Breuer J, Verjans GM. Cluster of Symptomatic Graft-to-Host Transmission of Herpes Simplex Virus Type 1 in an Endothelial Keratoplasty Setting. Ophthalmol Sci. 2021;1:100051. doi: 10.1016/j.xops.2021.100051.

• Petry M, Palus M, Leitzen E, Mitterreiter JG, Huang B, Kröger A, Verjans GM, Baumgärtner W, Rimmelzwaan GF, Růžek D, Osterhaus AD, Prajeeth CK. Immunity to TBEV Related Flaviviruses with Reduced Pathogenicity Protects Mice from Disease but Not from TBEV Entry into the CNS. Vaccines (Basel). 2021;9:196. doi: 10.3390/vaccines9030196.

• 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. High Levels of Neutrophil Extracellular Traps Persist in the Lower Respiratory Tract of Critically Ill Patients With Coronavirus Disease 2019. J Infect Dis. 2021;223:1512-1521. doi: 10.1093/infdis/jiab050.

• 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 JAA, Verjans GM, Koopmans MP, Muraro MJ, Peters PJ, Clevers H^**, Haagmans BL^**. An organoid-derived bronchioalveolar model for SARS-CoV-2 infection of human alveolar type II-like cells. EMBO J. 2021;40:e105912. doi: 10.15252/embj.2020105912.

• 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. Brain immune cells undergo cGAS/STING-dependent apoptosis during herpes simplex virus type 1 infection to limit type I IFN production. J Clin Invest. 2021;131:e136824. doi: 10.1172/JCI136824.

• Verdijk RM, Ouwendijk WJ, Kuijpers RW, Verjans GM. No Evidence of Varicella-Zoster Virus Infection in Temporal Artery Biopsies of Anterior Ischemic Optic Neuropathy Patients With and Without Giant Cell Arteritis. J Infect Dis. 2021;223:109-112. doi: 10.1093/infdis/jiaa566.

  2020

• Ouwendijk WJ^*, Depledge DP^*, Rajbhandari L, Lenac Rovis T, Jonjic S, Breuer J, Venkatesan A, Verjans GM, Sadaoka T. Varicella-zoster virus VLT-ORF63 fusion transcript induces broad viral gene expression during reactivation from neuronal latency. Nat Commun. 2020;11:6324. doi: 10.1038/s41467-020-20031-4.

• Braspenning SE, Sadaoka T, Breuer J, Verjans GM, Ouwendijk WJ^*, Depledge DP^*. Decoding the Architecture of the Varicella-Zoster Virus Transcriptome. mBio. 2020;11:e01568-20. doi: 10.1128/mBio.01568-20.

• 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. Alveolar barrier disruption in varicella pneumonia is associated with neutrophil extracellular trap formation. JCI Insight. 2020;5:e138900. doi: 10.1172/jci.insight.138900.

• Koetzier SC, van Langelaar J, Blok KM, van den Bosch TP, Wierenga-Wolf AF, Melief MJ, Pol K, Siepman TA, Verjans GM, Smolders J, Lubberts E, de Vries HE, van Luijn MM. Brain-homing CD4 T cells display glucocorticoid-resistant features in MS. Neurol Neuroimmunol Neuroinflamm. 2020;7:e894. doi: 10.1212/NXI.0000000000000894.

• Ouwendijk WJ, Dekker LJ, van den Ham HJ, Lenac Rovis T, Haefner ES, Jonjic S, Haas J, Luider TM, Verjans GM. Analysis of Virus and Host Proteomes During Productive HSV-1 and VZV Infection in Human Epithelial Cells. Front Microbiol. 2020;11:1179. doi: 10.3389/fmicb.2020.01179.

• Windster JD, Ouwendijk WJ, Sloots CEJ, Verjans GM, Verdijk RM. Ileocolic Intussusception as the Presenting Symptom of Primary Enteric Varicella-Zoster Virus Infection in a 7-Month-Old Infant. J Infect Dis. 2020;222:305-308. doi: 10.1093/infdis/jiaa148.

• 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. Large, Stable, Contemporary Interspecies Recombination Events in Circulating Human Herpes Simplex Viruses. J Infect Dis. 2020;221:1271-1279. doi: 10.1093/infdis/jiz199.

Collaborations within Erasmus MC

• Dept. Neurology
• Dept. Pathology
• Dept. Internal Medicine
• Dept. Neuroscience

Collaborations outside of Erasmus MC

• Rotterdam Eye Hospital (Rotterdam, The Netherlands)
• Netherlands Brain Bank (Amsterdam, The Netherlands)
• Stefanie Fruhwürth (University of Gothenburg, Sweden)
• David M. Koelle (University of Washington, Seattle, WA, USA)
• Daniel P. Depledge (Hannover Medical School, Hannover, Germany)
• Tomohiko Sadaoka (Kobe University Graduate School of Medicine, Kobe, Japan)
• Paul (Kip) R. Kinchington (University of Pittsburgh, Pittsburgh, PA, USA)
• Søren R. Paludan (Aarhus University Aarhus, Denmark)
• Stephen J. Elledge (Harvard Medical School, Boston, MA, USA)                    
  
   

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.

PhD POSITIONS

None at the moment

STUDENT INTERNSHIPS:

1. Evasion of T cell and NK cell immunity by varicella-zoster virus 
   (n=1 internship; already filled in until summer 2025)
2. Deciphering the role of herpes virus simplex reactive T‐cells in human corneas and sensory ganglia (n=1 internship; available September 2024)
3. Intrinsic immune control of neurotropic virus infections 
   (n=2 internships; available September 2024)
4. Trans-axonal transport of varicella-zoster virus
   (n=1 internship; already filled in until summer 2025) 
5. Chromatin Control of Varicella-Zoster Virus Latency and Reactivation
   (n=1 internship; already filled in until summer 2025)