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

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.

SUBMITTER: De Groof TWM

PROVIDER: S-EPMC8295288 | biostudies-literature | 2021 Jul

REPOSITORIES: biostudies-literature

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

De Groof Timo W M TWM Elder Elizabeth G EG Lim Eleanor Y EY Heukers Raimond R Bergkamp Nick D ND Groves Ian J IJ Wills Mark M Sinclair John H JH Smit Martine J MJ

Nature communications 20210721 1

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 immedia ...[more]

PMID: 34290252

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