Recombinant rabbit single-chain antibodies bind to the catalytic and C-terminal domains of HIV-1 integrase protein and strongly inhibit HIV-1 replication.
Biotechnol Appl Biochem
; 59(5): 353-66, 2012.
Article
em En
| MEDLINE
| ID: mdl-23586912
ABSTRACT
The human immunodeficiency virus type 1 (HIV-1) integrase (IN) protein plays an important role during the early stages of the retroviral life cycle and therefore is an attractive target for therapeutic intervention. We immunized rabbits with HIV-1 IN protein and developed a combinatorial single-chain variable fragment (scFv) library against IN. Five different scFv antibodies with high binding activity and specificity for IN were identified. These scFvs recognize the catalytic and C-terminal domains of IN and block the strand-transfer process. Cells expressing anti-IN-scFvs were highly resistant to HIV-1 replication due to an inhibition of the integration process itself. These results provide proof-of-concept that rabbit anti-IN-scFv intrabodies can be designed to block the early stages of HIV-1 replication without causing cellular toxicity. Therefore, these anti-IN-scFvs may be useful agents for "intracellular immunization"-based gene therapy strategies. Furthermore, because of their epitope binding characteristics, these scFvs can be used also as new tools to study the structure and function of HIV-1 IN protein.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Replicação Viral
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Proteínas Recombinantes
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HIV-1
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Integrase de HIV
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Domínio Catalítico
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Anticorpos de Cadeia Única
Tipo de estudo:
Prognostic_studies
Limite:
Animals
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Humans
Idioma:
En
Ano de publicação:
2012
Tipo de documento:
Article