Dr. D. A. J. (Debby) van Riel

Debby van Riel - Associate professor

Viral infections remain one of the greatest global health challenges, responsible for an immense burden of diseases worldwide. Viral infections can trigger disorders across multiple organ systems during the acute phase, but recent discoveries have revealed these infections can also result in lasting consequences.

Our mission is to uncover how viral infections drive disease progression—both during the acute phase and in the lingering post-acute period. For this we study a broad spectrum of (emerging) viruses, including respiratory viruses such as influenza A viruses, coronaviruses, and enterovirus D68, but also enteroviruses and monkeypox virus with research concentrated on four critical areas:

1. Cell tropism & viral factors – identifying which cells viruses target and the associated viral determinants
2. Systemic dissemination & inflammation – understanding how viruses spread beyond their primary replication site and trigger systemic immune responses
3. Neuropathogenesis: Routes of neuroinvasion – mapping the pathways viruses use to reach the central nervous system (CNS)
4. Neuropathogenesis: Neurotropism & neurovirulence – defining how viruses adapt to and damage neural tissues

Our findings have reshaped the understanding of respiratory viruses. We have demonstrated that many of them extend far beyond the respiratory tract, impacting the central nervous system and cardiovascular system. Notably, we have shown that nearly all influenza A viruses and SARS-CoV-2 can enter the CNS, where they provoke localized inflammatory responses that may persist long after the initial infection.

By integrating in vivo and advanced stem cell-derived in vitro models, we dissect virus–host interactions from the molecular scale to the whole-organism level. This comprehensive approach allows us to reveal mechanisms that underpin both immediate and long-term disease outcomes.

You can follow Debby on:
1. LinkedIn
2. BlueSky

Recent key publication on the neuropathogenesis of viruses:

1. Attachment and replication of clade 2.3.4.4b influenza A (H5N1) viruses in human respiratory epithelium: an in-vitro study. Lisa Bauer, Lonneke Leijten, Matteo Iervolino, Varun Chopra, Laura van Dijk, Mark Power, Willemijn Rijnink, Mark Pronk, Monique Spronken, Mathis Funk, Rory D de Vries, Mathilde Richard, Thijs Kuiken, Debby van Riel. Lancet Microbe in press.
2. The neuropathogenesis of highly pathogenic avian influenza H5Nx viruses in mammalian species including humans.
   Bauer L, Benavides FFW, Veldhuis Kroeze EJB, de Wit E, van Riel D. Trends Neurosci. 2023 Sep 6:S0166-2236(23)00190-X. doi: 10.1016/j.tins.2023.08.002
3. Evolution of highly pathogenic H5N1 influenza A virus in the central nervous system of ferrets.
   Siegers JY, Ferreri L, Eggink D, Veldhuis Kroeze EJB, Te Velthuis AJW, van de Bildt M, Leijten L, van Run P, de Meulder D, Bestebroer T, Richard M, Kuiken T, Lowen AC, Herfst S, van Riel D. PLoS Pathog. 2023 Mar 10;19(3):e1011214. doi: 10.1371/journal.ppat.1011214
4. In vitro and in vivo differences in neurovirulence between D614G, Delta And Omicron BA.1 SARS-CoV-2 variants.
   Bauer L, Rissmann M, Benavides FFW, Leijten L, van Run P, Begeman L, Veldhuis Kroeze EJB, Lendemeijer B, Smeenk H, de Vrij FMS, Kushner SA, Koopmans MPG, Rockx B, van Riel D. Acta Neuropathol Commun. 2022 Sep 5;10(1):124. doi: 10.1186/s40478-022-01426-4.

5. A High-Fat Diet Increases Influenza A Virus-Associated Cardiovascular Damage.
   Siegers JY, Novakovic B, Hulme KD, Marshall RJ, Bloxham CJ, Thomas WG, Reichelt ME, Leijten L, van Run P, Knox K, Sokolowski KA, Tse BWC, Chew KY, Christ AN, Howe G, Bruxner TJC, Karolyi M, Pawelka E, Koch RM, Bellmann-Weiler R, Burkert F, Weiss G, Samanta RJ, Openshaw PJM, Bielefeldt-Ohmann H, van Riel D, Short KR.J Infect Dis. 2020 Aug 4;222(5):820-831. doi: 10.1093/infdis/jiaa159.PMID: 32246148

6. 1918 H1N1 Influenza Virus Replicates and Induces Proinflammatory Cytokine Responses in Extrarespiratory Tissues of Ferrets.
   de Wit E, Siegers JY, Cronin JM, Weatherman S, van den Brand JM, Leijten LM, van Run P, Begeman L, van den Ham HJ, Andeweg AC, Bushmaker T, Scott DP, Saturday G, Munster VJ, Feldmann H, van Riel D. J Infect Dis. 2018 Mar 28;217(8):1237-1246. doi: 10.1093/infdis/jiy003.PMID: 29329410

7. Vaccination Is More Effective Than Prophylactic Oseltamivir in Preventing CNS Invasion by H5N1 Virus via the Olfactory Nerve.
   Siegers JY, van den Brand JM, Leijten LM, van de Bildt MM, van Run PR, van Amerongen G, Stittelaar KJ, Koopmans MP, Osterhaus AD, Kuiken T, van Riel D. J Infect Dis. 2016 Aug 15;214(4):516-24. doi: 10.1093/infdis/jiw123. Epub 2016 Apr 1.PMID: 27448390

8. H5N1 Virus Attachment to Lower Respiratory Tract.
   van Riel D, Munster VJ, de Wit E, Rimmelzwaan GF, Fouchier RA, Osterhaus AD, Kuiken T.Science. 2006 Apr 21;312(5772):399. doi: 10.1126/science.1125548. Epub 2006 Mar 23.PMID: 16556800

Recent publications on the systemic pathogenesis of viruses

1. Elucidating the role of human skeletal muscles in the pathogenesis of enterovirus D68 infection.
   Laksono BM, Bergsma AJ, Iuliano A, Veldhoen DY, van Nieuwkoop S, Boter M, Leijten L, Bauer L, Oude Munnink BB, Pijnappel WP, van Riel D. Life Sci Alliance. 2025 Sep 5;8(11):e202503372. doi: 10.26508/lsa.202503372. Print 2025 Nov.PMID: 40912913
2. Attachment Patterns of Avian Influenza H5 Clade 2.3.4.4b Virus in Respiratory Tracts of Marine Mammals, North Atlantic Ocean
   Sooksawasdi Na Ayudhya S, Leijten L, Rijnink WF, Spronken MI, Kuiken T, Bauer L, van Riel D. Emerg Infect Dis. 2025 Sep;31(9):1729-1737. doi: 10.3201/eid3109.250499. Epub 2025 Aug 5.PMID: 40764708
3. Sialic Acid-Containing Glycolipids Extend the Receptor Repertoire of Enterovirus-D68.
   Pereirinha da Silva AK, van Trijp JP, Montenarie A, Fok JA, Sooksawasdi Na Ayudhya S, Pieters RJ, Boons GJ, van Riel D, de Vries RP, Bauer L. ACS Infect Dis. 2025 Aug 8;11(8):2090-2103. doi: 10.1021/acsinfecdis.5c00063. Epub 2025 Jul 9.PMID: 40633911
4. Neuroinvasive and neurovirulent potential of SARS-CoV-2 in the acute and post-acute phase of intranasally inoculated ferrets.
   Benavides FFW, Veldhuis Kroeze EJB, Leijten L, Schmitz KS, van Run P, Kuiken T, de Vries RD, Bauer L, van Riel D. PLoS One. 2025 Apr 7;20(4):e0311449. doi: 10.1371/journal.pone.0311449. eCollection 2025.PMID: 40193353
5. Differential susceptibility of human motor neurons to infection with Usutu and West Nile virus.
   Marshall EM, Bauer L, Nelemans T, Sooksawasdi Na Ayudhya S, Benavides F, Lanko K, de Vrij FMS, Kushner SA, Koopmans M, van Riel D, Rockx B.J Neuroinflammation. 2024 Sep 27;21(1):236. doi: 10.1186/s12974-024-03228-y.PMID: 39334427
6. Cellular Importin-α3 Expression Dynamics in the Lung Regulate Antiviral Response Pathways against Influenza A Virus Infection.
   Thiele S, Stanelle-Bertram S, Beck S, Kouassi NM, Zickler M, Müller M, Tuku B, Resa-Infante P, van Riel D, Alawi M, Günther T, Rother F, Hügel S, Reimering S, McHardy A, Grundhoff A, Brune W, Osterhaus A, Bader M, Hartmann E, Gabriel G. Cell Rep. 2024 Apr 23;43(4):114023. doi: 10.1016/j.celrep.2024.114023. Epub 2024 Mar 22.PMID: 38520692
7. Species-specific emergence of H7 highly pathogenic avian influenza virus is driven by intrahost selection differences between chickens and ducks.
   de Bruin ACM, Spronken MI, Kok A, Rosu ME, de Meulder D, van Nieuwkoop S, Lexmond P, Funk M, Leijten LM, Bestebroer TM, Herfst S, van Riel D, Fouchier RAM, Richard M.PLoS Pathog. 2024 Feb 26;20(2):e1011942. doi: 10.1371/journal.ppat.1011942. eCollection 2024 Feb.PMID: 38408092
8. Functional properties of measles virus proteins derived from a subacute sclerosing panencephalitis patient who received repeated remdesivir treatments.
   Schmitz KS, Handrejk K, Liepina L, Bauer L, Haas GD, van Puijfelik F, Veldhuis Kroeze EJB, Riekstina M, Strautmanis J, Cao H, Verdijk RM, GeurtsvanKessel CH, van Boheemen S, van Riel D, Lee B, Porotto M, de Swart RL, de Vries RD. J Virol. 2024 Mar 19;98(3):e0187423. doi: 10.1128/jvi.01874-23. Epub 2024 Feb 8.PMID: 38329336
9. Human B cells and dendritic cells are susceptible and permissive to enterovirus D68 infection.
   Laksono BM, Sooksawasdi Na Ayudhya S, Aguilar-Bretones M, Embregts CWE, van Nierop GP, van Riel D. mSphere. 2024 Feb 28;9(2):e0052623. doi: 10.1128/msphere.00526-23. Epub 2024 Jan 23.PMID: 38259063
10. CYP19A1 mediates severe SARS-CoV-2 disease outcome in males.
    Stanelle-Bertram S, Beck S, Mounogou NK, Schaumburg B, Stoll F, Al Jawazneh A, Schmal Z, Bai T, Zickler M, Beythien G, Becker K, de la Roi M, Heinrich F, Schulz C, Sauter M, Krasemann S, Lange P, Heinemann A, van Riel D, Leijten L, Bauer L, van den Bosch TPP, Lopuhaä B, Busche T, Wibberg D, Schaudien D, Goldmann T, Lüttjohann A, Ruschinski J, Jania H, Müller Z, Pinho Dos Reis V, Krupp-Buzimkic V, Wolff M, Fallerini C, Baldassarri M, Furini S, Norwood K, Käufer C, Schützenmeister N, von Köckritz-Blickwede M, Schroeder M, Jarczak D, Nierhaus A, Welte T, Kluge S, McHardy AC, Sommer F, Kalinowski J, Krauss-Etschmann S, Richter F, von der Thüsen J, Baumgärtner W, Klingel K, Ondruschka B; GEN-COVID Multicenter Study Group; Renieri A, Gabriel G.Cell Rep Med. 2023 Sep 19;4(9):101152. doi: 10.1016/j.xcrm.2023.101152.
11. The pro-inflammatory response to influenza A virus infection is fueled by endothelial cells.
    Bauer L, Rijsbergen LC, Leijten L, Benavides FF, Noack D, Lamers MM, Haagmans BL, de Vries RD, de Swart RL, van Riel D. Life Sci Alliance. 2023 Apr 18;6(7):e202201837
12. The pathogenesis of zoonotic viral infections: Lessons learned by studying reservoir hosts.
    Begeman L, van Riel D, Koopmans MPG, Kuiken T. Front Microbiol. 2023 Mar 28;14:1151524. doi: 10.3389/fmicb.2023.1151524. eCollection 2023.PMID: 37056741
13. Evolution of highly pathogenic H5N1 influenza A virus in the central nervous system of ferrets.
    Siegers JY, Ferreri L, Eggink D, Veldhuis Kroeze EJB, Te Velthuis AJW, van de Bildt M, Leijten L, van Run P, de Meulder D, Bestebroer T, Richard M, Kuiken T, Lowen AC, Herfst S, van Riel D. PLoS Pathog. 2023 Mar 10;19(3):e1011214. doi: 10.1371/journal.ppat.1011214. eCollection 2023 Mar.PMID: 36897923
14. Rescue and in vitro characterization of a divergent TBEV-Eu strain from the Netherlands.
    Hoornweg TE, Godeke GJ, Hoogerwerf MN, van Kasteren PB, de Vries A, Sprong H, Verjans GMGM, van Riel D, Reimerink JHJ, Rockx B, Reusken CBEM.Sci Rep. 2023 Feb 18;13(1):2872. doi: 10.1038/s41598-023-29075-0.PMID: 36807371
15. Do SARS-CoV-2 Variants Differ in Their Neuropathogenicity?
    Bauer L, van Riel D. mBio. 2023 Feb 28;14(1):e0292022. doi: 10.1128/mbio.02920-22. Epub 2023 Jan 18.PMID: 36651750
16. Pulmonary lesions following inoculation with the SARS-CoV-2 Omicron BA.1 (B.1.1.529) variant in Syrian golden hamsters.
    Rissmann M, Noack D, van Riel D, Schmitz KS, de Vries RD, van Run P, Lamers MM, Geurts van Kessel CH, Koopmans MPG, Fouchier RAM, Kuiken T, Haagmans BL, Rockx B.Emerg Microbes Infect. 2022 Dec;11(1):1778-1786. doi: 10.1080/22221751.2022.2095932.PMID: 35787236
17. Detection of intrathecal antibodies to diagnose enterovirus infections of the central nervous system.
    Sooksawasdi Na Ayudhya S, Sips GJ, Bogers S, Leijten LME, Laksono BM, Smeets LC, Bruning A, Benschop K, Wolthers K, van Riel D, GeurtsvanKessel CH.J Clin Virol. 2022 Jul;152:105190. doi: 10.1016/j.jcv.2022.105190. Epub 2022 May 23.PMID: 35640402
18. The neuroinvasiveness, neurotropism, and neurovirulence of SARS-CoV-2.
    Bauer L, Laksono BM, de Vrij FMS, Kushner SA, Harschnitz O, van Riel D. Trends Neurosci. 2022 May;45(5):358-368. doi: 10.1016/j.tins.2022.02.006. Epub 2022 Mar 3.PMID: 35279295

Funding

Debby has received several grants and fellowships that support her research group, including a Veni, Erasmus MC fellowship, Vidi, EUR fellowship and Aspasia. In addition, she has been involved in different EU consortia like FLUPIG, ANTIGONE, and is currently involved in the EU consortia KAPPA-FLU and REFINE. Lastly, Debby is coordinator of the NWO-XL consortium Viruses like it sweet; virus-glycan interactions as determinants of host range and pathogenesis | NWO

Awards

Debby received the Beijerinck premium in 2015 (2 yearly award for promising early career scientists within virology research in the Netherlands), the ESWI Award in 2017 (3-yearly international awards for the most promising body of work in influenza virus research from European Scientific Working group on Influenza) and she is a former member of the Young Erasmus Academy and the young scientist ambassador at the ESWI.

1. Kappa-Flu: Startseite kappa flu
   
   
2. REFINE: REFINE – REFINE is a collaboration between 4 European and 2 Australian partners that aims to enhance treatments for mosquito-borne orthoflavivirus infections by identifying new targets for antibodies, inhibitors, and vaccines.
   
3. Viruses like it sweet: Viruses like it sweet; virus-glycan interactions as determinants of host range and pathogenesis | NWO
   
   
4. Prof. Dr. Gülsah Gabriel, Leibniz Institute of Virology, Hamburg, Germany:
   Debby is employed as a guest scientist at the HPI and resulted in several joint publications (Stanelle-Bertram S 2024; Stanelle-Bertram S 2023; Thiele 2020; Anfasa 2017; Betram 2017; van Riel 2016; Otte 2016 and Siegers 2014)
   
   
5. Dr. Emmie de Wit, RML NIH, Montana US:
   Collaboration on the (neuro) pathogenesis of respiratory viruses and resulted in several joint publications (Bauer 2023; van Riel 2020; Munster 2020; te Velthuis 2018; de Wit 2018; Chutinimitkul 2010; van Riel 2010; de Wit 2010; van Riel 2007; Munster 2007; van Riel 2006).
   
   
6. Dr. Femke de Vrij and Prof. Kushner, department of Psychiatry, Erasmus MC, The Netherlands:
   Collaboration on the development of human induced pluripotent stem cell derived neural models to study the neuropathogenesis of viral infections. Resulted in several joint publications (Marschall 2024; Bauer 2023; Bauer 2022; Bauer 2022; Bauer 2021; Anfasa 2017).
   
   
7. Dr Oliver Harschnitz, Human Technopole, Milan, Italy: 
   Collaboration on how viruses affect the neural homeostasis using stem cell based neural models, which resulted in 2 joint publications so far (Bauer 2023; Bauer 2022).

 The RielScience team consists out of the following amazing people:

Debby van Riel – PI, Associate Professor Lisa Bauer – Assistant Professor Edwin Veldhuis-Kroeze- Veterinary Pathologist Lonneke Leijten – Research technician Feline Benavides – PhD student Matteo Iervolino – PhD student Ashley Pereirinha da Silva – PhD student Zoë Krullaars – PhD student Lara Danijs – BSc student Anne-Marthe Woldhuis – BSc student Eline Potman – MSc student