Targeting the latent human cytomegalovirus reservoir for T-cell-mediated killing with virus-specific nanobodies.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 34290252.
- Also identified by DOI 10.1038/s41467-021-24608-5 and PMC identifier 8295288.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
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.
Medical subject headings
- Cytomegalovirus
- Single-Domain Antibodies
- T-Lymphocytes, Cytotoxic
- Virus Latency