A chemical method for generating live-attenuated, replication-defective DNA viruses for vaccine development.
Cell Rep Methods
; 2(9): 100287, 2022 09 19.
Article
em En
| MEDLINE
| ID: mdl-36160049
ABSTRACT
The development of a chemically attenuated, replication-incompetent virus vaccine can provide protection against diseases caused by DNA viruses. In this study, we have developed a method to produce live-attenuated, replication-defective viruses using centanamycin (CM), a chemical compound that alkylates the A-T-rich minor groove of the DNA and thereby blocks DNA replication. We tested the efficacy of CM to produce live-attenuated, replication-defective human cytomegalovirus, mouse cytomegalovirus, and herpes simplex virus-2 (HSV-2), suggesting a broad application for generating live-attenuated, replication-defective DNA viruses. Mass spectrometry analysis showed that CM alkylate viral DNA at the adenine-N3 position. Moreover, mice immunization with CM-attenuated mouse cytomegalovirus (MCMV) produced a robust immune response and reduced the viral load in immunized animals against challenges with live, wild-type MCMV. Our study offers a unifying and attractive therapeutic opportunity that chemically attenuated live DNA viruses can be readily developed as new frontline vaccines.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Imunização
/
Herpesvirus Humano 2
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Cell Rep Methods
Ano de publicação:
2022
Tipo de documento:
Article
País de afiliação:
Estados Unidos