학술논문
Recombinant rabbit single-chain antibodies bind to the catalytic and C-terminal domains of HIV-1 integrase protein and strongly inhibit HIV-1 replication
Document Type
Academic Journal
Author
Source
Biotechnology and Applied Biochemistry. Sep 01, 2012 59(5):353-366
Subject
Language
English
ISSN
0885-4513
Abstract
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.