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

Timo W. M. De Groof, Elizabeth G. Elder, Eleanor Y. Lim, Raimond Heukers, Nick D. Bergkamp, Ian J. Groves, Mark Wills, John H. Sinclair and Martine J. Smit ()
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Timo W. M. De Groof: VU University, De Boelelaan 1108
Elizabeth G. Elder: University of Cambridge
Eleanor Y. Lim: University of Cambridge
Raimond Heukers: VU University, De Boelelaan 1108
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

Nature Communications, 2021, vol. 12, issue 1, 1-11

Abstract: 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.

Date: 2021
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DOI: 10.1038/s41467-021-24608-5

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