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Targeting the latent human cytomegalovirus reservoir for T-cell-mediated killing with virus-specific nanobodies

Author

Listed:
  • Timo W. M. De Groof

    (VU University, De Boelelaan 1108
    Vrije Universiteit Brussel (VUB), Laarbeeklaan 103)

  • Elizabeth G. Elder

    (University of Cambridge
    Public Health Agency of Sweden, Nobels väg 18)

  • Eleanor Y. Lim

    (University of Cambridge)

  • Raimond Heukers

    (VU University, De Boelelaan 1108
    QVQ Holding BV, Yalelaan 1)

  • Nick D. Bergkamp

    (VU University, De Boelelaan 1108)

  • Ian J. Groves

    (University of Cambridge)

  • Mark Wills

    (University of Cambridge)

  • John H. Sinclair

    (University of Cambridge)

  • Martine J. Smit

    (VU University, De Boelelaan 1108)

Abstract

Latent human cytomegalovirus (HCMV) infection is characterized by limited gene expression, making latent HCMV infections refractory to current treatments targeting viral replication. However, reactivation of latent HCMV in immunosuppressed solid organ and stem cell transplant patients often results in morbidity. Here, we report the killing of latently infected cells via a virus-specific nanobody (VUN100bv) that partially inhibits signaling of the viral receptor US28. VUN100bv reactivates immediate early gene expression in latently infected cells without inducing virus production. This allows recognition and killing of latently infected monocytes by autologous cytotoxic T lymphocytes from HCMV-seropositive individuals, which could serve as a therapy to reduce the HCMV latent reservoir of transplant patients.

Suggested Citation

  • Timo W. M. De Groof & Elizabeth G. Elder & Eleanor Y. Lim & Raimond Heukers & Nick D. Bergkamp & Ian J. Groves & Mark Wills & John H. Sinclair & Martine J. Smit, 2021. "Targeting the latent human cytomegalovirus reservoir for T-cell-mediated killing with virus-specific nanobodies," Nature Communications, Nature, vol. 12(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-24608-5
    DOI: 10.1038/s41467-021-24608-5
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