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

Autor: Nick D. Bergkamp, Raimond Heukers, Eleanor Y. Lim, John Sinclair, Ian J. Groves, Elizabeth G. Elder, Mark R. Wills, Martine J. Smit, Timo W.M. De Groof
Přispěvatelé: De Groof, Timo WM [0000-0001-6918-2955], Elder, Elizabeth G [0000-0003-1615-2642], Heukers, Raimond [0000-0003-4498-7751], Groves, Ian J [0000-0001-8882-6701], Smit, Martine J [0000-0003-2713-0238], Apollo - University of Cambridge Repository, De Groof, Timo W M [0000-0001-6918-2955], De Groof, Timo W. M. [0000-0001-6918-2955], Elder, Elizabeth G. [0000-0003-1615-2642], Groves, Ian J. [0000-0001-8882-6701], Smit, Martine J. [0000-0003-2713-0238], Supporting clinical sciences, Medicinal chemistry, AIMMS
Rok vydání: 2021
Předmět:
0301 basic medicine
Human cytomegalovirus
viruses
631/326/596
96
Lipopolysaccharide Receptors
General Physics and Astronomy
Cytomegalovirus
Gene Expression
639/925/352/152
Monocytes
0302 clinical medicine
Cytotoxic T cell
Cells
Cultured
Multidisciplinary
article
virus diseases
food and beverages
humanities
Virus Latency
medicine.anatomical_structure
030220 oncology & carcinogenesis
38/35
Cytomegalovirus Infections
38/77
Receptors
Chemokine
Stem cell
Infection
82/1
Signal Transduction
Science
T cell
13/106
Biology
General Biochemistry
Genetics and Molecular Biology
Virus
96/95
03 medical and health sciences
Viral Proteins
SDG 3 - Good Health and Well-being
Virology
medicine
Humans
Genes
Immediate-Early
Innate immune system
692/420/254
fungi
General Chemistry
biochemical phenomena
metabolism
and nutrition
Single-Domain Antibodies
medicine.disease
030104 developmental biology
Viral replication
Viral Receptor
Drug delivery
Virus Activation
T-Lymphocytes
Cytotoxic
Zdroj: Nature Communications
De Groof, T W M, Elder, E G, Lim, E Y, Heukers, R, Bergkamp, N D, Groves, I J, Wills, M, Sinclair, J H & Smit, M J 2021, ' Targeting the latent human cytomegalovirus reservoir for T-cell-mediated killing with virus-specific nanobodies ', Nature Communications, vol. 12, 4436, pp. 1-11 . https://doi.org/10.1038/s41467-021-24608-5
Nature Communications, 12:4436, 1-11. Nature Publishing Group
Nature Communications, Vol 12, Iss 1, Pp 1-11 (2021)
ISSN: 2041-1723
DOI: 10.1038/s41467-021-24608-5
Popis: 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.
Human cytomegalovirus (HCMV) can evade immune responses in latent reservoirs, which is a specific problem during transplantation. Here the authors develop a bivalent nanobody that is specific for US28, a viral receptor required by latent HCMV, and show it can partially reactivate the virus and make it susceptible to killing by T cells.
Databáze: OpenAIRE
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