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Journal of General Virology header logo Journal of General Virology

Volume 106, Issue 4

Characterization of human cytomegalovirus infection dynamics in human microglia Open Access

Abstract

Human cytomegalovirus (HCMV) is a β-herpesvirus that establishes asymptomatic infections in immunocompetent individuals but can cause severe or even life-threatening symptoms in immunocompromised patients. HCMV can replicate in a wide variety of cells through the engagement of diverse cell factors with the viral envelope protein gH/gL/gO (trimer) or gH/gL/UL128/UL130/UL131a (pentamer), allowing for systemic spread within the human host. This study explores HCMV infection tropism and dynamics in human microglia, demonstrating the susceptibility of microglia to both clinical and laboratory HCMV strains, with lower efficacy for the laboratory strain, implying that both the gH/gL-trimer and -pentamer can mediate virus entry in microglia. The importance of the gH/gL pentamer for virus entry was demonstrated by the inhibition of virus infection upon pre-incubation with a soluble neuropilin-2 (NRP-2) entry factor. Further, we demonstrated that HCMV infection can be effectively inhibited by monoclonal antibodies specific for the gH/gL complexes and HCMV hyperimmunoglobulin. Lastly, we report that microglia infection can be prevented by newly characterized chemical entry inhibitors. Altogether, these findings underscore the potential of microglia as valuable models for studying HCMV neurotropism and strategies to block virus infection in cells that can impact neurological disorders.

  • Received:
  • Accepted:
  • Published Online:
Keyword(s): tropism , antibodies , entry inhibitors , human cytomegalovirus , microglia and neuropilin-2 (NRP-2)
Funding
This study was supported by the:
  • Division of Microbiology and Infectious Diseases, National Institute of Allergy and Infectious Diseases (Award R56AI175974)
    • Principal Award Recipient: DomenicoTortorella
  • Division of Microbiology and Infectious Diseases, National Institute of Allergy and Infectious Diseases (Award R56AI174062)
    • Principal Award Recipient: DomenicoTortorella
  • Cure Alzheimer's Fund
    • Principal Award Recipient: SamGandy
  • Cure Alzheimer's Fund
    • Principal Award Recipient: MichelleE Ehrlich
  • Division of Microbiology and Infectious Diseases, National Institute of Allergy and Infectious Diseases (Award AI R56174062)
    • Principal Award Recipient: JAndrew Duty
  • Division of Microbiology and Infectious Diseases, National Institute of Allergy and Infectious Diseases (Award AI R56174062, R01AI139258, R21AI147632, and RF1AG059319)
    • Principal Award Recipient: DomenicoTortorella
  • Division of Microbiology and Infectious Diseases, National Institute of Allergy and Infectious Diseases (Award T32-AI007647, AI R56174062)
    • Principal Award Recipient: KristinaE Atanasoff
  • National Institute on Aging (Award RF1AG059319)
    • Principal Award Recipient: TajudeenO. Jimoh
  • National Institute on Aging (Award U01AG046170, RF1AG058469, RF1AG059319, R01AG061894, P30 AG066514)
    • Principal Award Recipient: SamGandy
  • National Institute on Aging (Award U01AG046170, RF1AG058469, RF1AG059319, R01AG061894, P30 AG066514)
    • Principal Award Recipient: MichelleE Ehrlich
  • Spanish Ministry of Science (Award FPU19/05927)
    • Principal Award Recipient: MarcosNuevalos Guaita
© 2025 The Authors
  • This is an open-access article distributed under the terms of the Creative Commons Attribution License. This article was made open access via a Publish and Read agreement between the Microbiology Society and the corresponding author’s institution.
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2025-04-29
2025-11-12

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Characterization of human cytomegalovirus infection dynamics in human microglia
J. Gen. Virol. 106, 002096 (2025); https://doi.org/10.1099/jgv.0.002096
/content/journal/jgv/10.1099/jgv.0.002096
/content/journal/jgv/10.1099/jgv.0.002096
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