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Microglial MARCO facilitates Varicella zoster virus uptake and triggers TLR2-mediated neuroinflammation.

Overview

Authors: Ji-Soo Lim1, Soo-Jin Oh1, Ji-Yeun Hur2, Subin Oh3, Seuk-Min Ryu4, Rafael T Han3,5, Hosun Park6, Dawn M E Bowdish7, Ok Sarah Shin1,8
ORCID iDs: Ji-Yeun Hur
  1. BK21 Graduate Program, Department of Biomedical Sciences, Korea University College of Medicine, Seoul, Korea
  2. Department of Biological Sciences, Ajou University, Suwon, Korea
  3. Biomedical Research Division, Korea Institute of Science and Technology (KIST), Seoul, Korea
  4. Center for Advanced Biomolecular Recognition, Biomedical Research Division, Korea Institute of Science and Technology (KIST), Seoul, Korea
  5. KHU-KIST Department of Converging Science and Technology, Kyung Hee University, Seoul, Korea
  6. Department of Microbiology, College of Medicine, Yeungnam University, Daegu, Korea
  7. Department of Medicine, McMaster University, Hamilton, ON Canada
  8. Vaccine Innovation Center, Korea University College of Medicine, Seoul, Korea
Institutions: Korea University (South Korea); Korea Institute of Science and Technology (South Korea); Ajou University (South Korea); Kyung Hee University (South Korea); Yeungnam University College; Yeungnam University (South Korea); McMaster University (Canada); Korea University Medical Center (South Korea)
Journal: Journal of biomedical science, volume 33, issue 1, article 53
Dates: received 9 October 2025; accepted 12 May 2026; published online 23 May 2026
Type: Research article · Language: English
License: CC BY
Identifiers: DOI 10.1186/s12929-026-01256-9 · PMID 42177488 · PMCID PMC13198062 · OpenAlex W7162212453
Open access: diamond, a free copy (OpenAlex)
Status: data only
Categories: human (organism), other condition (population), pain (population), cellular / molecular (subfield)
Methods: Statistics
Keywords: Varicella zoster virus, MARCO, TLR2, Microglia, Sensory neurons
MeSH: Herpesvirus 3, Human*, Microglia*, Neuroinflammatory Diseases*, Receptors, Immunologic*, Toll-Like Receptor 2*, Varicella Zoster Virus Infection*, Cell Line, Humans (* major topic)
Topic: Herpesvirus Infections and Treatments (Epidemiology, Medicine), according to OpenAlex
Funding: National Research Foundation of Korea
Citations: not cited yet (Europe PMC); 68 references in the paper

Abstract

Background: Varicella zoster virus (VZV) is a human neurotropic virus that can establish latency in sensory neurons. Microglia play a complex role during neurotropic virus infections; however, their role during VZV infection remains to be determined. In the present study, we explored the role of VZV-induced alterations in the morphodynamics and function of microglia in triggering neuroinflammation.

Methods: We prepared cell-free VZV and compared replication efficiencies of wild-type (YC01) and attenuated (MAV/06, MAV) VZV in two transformed human microglial cell lines (HMC3 and HIM) and human embryonic stem cell (ESC)-derived microglia (ESC-MG). Bulk RNA sequencing was used to assess molecular signatures of microglia following VZV infection in ESC-MG, and cytokine profiles were determined to further investigate neuroinflammation. To further examine the impact of VZV-induced microglial inflammation on neuronal responses, we generated ESC-derived sensory neurons (ESC-SN) and evaluated nociceptor expression and calcium flux as a readout for SN activities following microglial secretome treatment.

Results: VZV upregulates its gene and protein expression and triggered morphological changes in various microglia cultures. Transcriptomic analysis of YC01-infected ESC-MG revealed a robust induction of genes associated with antiviral innate immunity, alongside a pronounced upregulation of macrophage receptor with collagenous structure (MARCO). Functional studies demonstrated that MARCO facilitates VZV uptake in microglia by binding to the viral glycoprotein E (gE) via its C-terminal scavenger receptor cysteine-rich (SRCR) domain, thereby promoting viral entry and phagocytosis. Moreover, VZV infection elicited neuroinflammation in an ORF62-dependent manner, while MARCO activation triggered toll-like receptor 2 (TLR2)-mediated inflammatory signaling. This cascade further amplified the expression of pain-associated molecular mediators in an ESC-SN model, highlighting a potential mechanistic link between microglial MARCO and VZV-triggered neuropathic processes.

Conclusion: Our results show, for the first time, that microglia are susceptible to VZV infection and identify MARCO as an important mediator for regulating TLR2-mediated neuroinflammation and promoting an upregulation of factors associated with neuropathic pain.

Supplementary Information: The online version contains supplementary material available at 10.1186/s12929-026-01256-9.

Reproduced under the paper's license (CC BY), from the paper cited above.

Code

The paper links to its data, not to its authors' code: see the Data section.

Tracing map

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Data

Datasets cited

Data availability

The datasets generated during the current study are available in the GEO repository under accession number GSE309260 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE309260).

Reproduced under the paper's license (CC BY), from the paper cited above.

Versions

The history of this record: each version stored by the harvester or made by a correction of its authors or of the maintainers of its code, and what changed in its facts. The texts of the paper (its abstract, its availability statements) are not part of it; versions that changed only those are not listed.

Version 1, 28 September 2026: the first record

Recorded: type, language, journal, volume, issue, pages, dates, 9 authors, 5 keywords, 8 MeSH terms, 1 funder, 68 references.

Cite

This paper

Lim, J.-S., Oh, S.-J., Hur, J.-Y., Oh, S., Ryu, S.-M., Han, R. T., Park, H., Bowdish, D. M. E., & Shin, O. S. (2026). Microglial MARCO facilitates Varicella zoster virus uptake and triggers TLR2-mediated neuroinflammation. Journal of biomedical science, 33(1), 53. https://doi.org/10.1186/s12929-026-01256-9

BibTeX

@article{lim2026microglial,
author = {Lim, Ji-Soo and Oh, Soo-Jin and Hur, Ji-Yeun and Oh, Subin and Ryu, Seuk-Min and Han, Rafael T and Park, Hosun and Bowdish, Dawn M E and Shin, Ok Sarah},
title = {{Microglial MARCO facilitates Varicella zoster virus uptake and triggers TLR2-mediated neuroinflammation}},
journal = {Journal of biomedical science},
year = {2026},
month = may,
volume = {33},
number = {1},
pages = {53},
publisher = {BMC},
issn = {1021-7770},
doi = {10.1186/s12929-026-01256-9},
url = {https://doi.org/10.1186/s12929-026-01256-9},
pmid = {42177488},
pmcid = {PMC13198062}
}

RIS

TY - JOUR
AU - Lim, Ji-Soo
AU - Oh, Soo-Jin
AU - Hur, Ji-Yeun
AU - Oh, Subin
AU - Ryu, Seuk-Min
AU - Han, Rafael T
AU - Park, Hosun
AU - Bowdish, Dawn M E
AU - Shin, Ok Sarah
TI - Microglial MARCO facilitates Varicella zoster virus uptake and triggers TLR2-mediated neuroinflammation
T2 - Journal of biomedical science
J2 - J Biomed Sci
PY - 2026
DA - 2026/05/23
VL - 33
IS - 1
SP - 53
SN - 1021-7770
PB - BMC
DO - 10.1186/s12929-026-01256-9
UR - https://doi.org/10.1186/s12929-026-01256-9
LA - en
ER -

CSL-JSON

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