title: COP9 signalosome subunit 6 binds and inhibits avian leukosis virus integrase.
abstract: The retroviral integrase plays an essential role in the integration of reverse-transcribed retroviral cDNA into the host cell genome, and serves as an important target for anti-viral therapeutics. In this study, we identified the COP9 signalosome subunit 6 (CSN6) as a novel avian leukosis virus (ALV) integrase binding protein. Co-immunoprecipitation and GST pull-down assays showed that CSN6 bound to ALV integrase likely through direct interaction of CSN6 to the catalytic core of the integrase. We further demonstrated CSN6 inhibited integrase activity in vitro; knockdown of CSN6 in DF-1 promoted ALV production. These results indicated that CSN6 may be a negative regulator of ALV replication by binding to and inhibiting integrase. Our findings provided the insight into the integrase-based host defense system and may have implications in the development of integrase-based anti-viral strategies.
authors.affiliation: State Key Laboratory of Agrobiotechnology, China Agricultural University, Beijing 100193, China; College of Veterinary Medicine, China Agricultural University, Beijing 100193, China.
authors.forename: Zhanxin
authors.initials: Z
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Agrobiotechnology, China Agricultural University, Beijing 100193, China; College of Veterinary Medicine, China Agricultural University, Beijing 100193, China.
authors.forename: Aotian
authors.initials: A
authors.lastname: Xu
authors.affiliation: State Key Laboratory of Agrobiotechnology, China Agricultural University, Beijing 100193, China; College of Veterinary Medicine, China Agricultural University, Beijing 100193, China.
authors.forename: Xinhui
authors.initials: X
authors.lastname: Hou
authors.affiliation: College of Veterinary Medicine, China Agricultural University, Beijing 100193, China.
authors.forename: Fuyong
authors.initials: F
authors.lastname: Chen
authors.affiliation: Key Laboratory of Animal Disease Control and Prevention of the Ministry of Agriculture, College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, China.
authors.forename: Weisheng
authors.initials: W
authors.lastname: Cao
authors.affiliation: State Key Laboratory of Agrobiotechnology, China Agricultural University, Beijing 100193, China; College of Veterinary Medicine, China Agricultural University, Beijing 100193, China.
authors.forename: Jieshi
authors.initials: J
authors.lastname: Yu
authors.affiliation: Key Laboratory of Animal Disease Control and Prevention of the Ministry of Agriculture, College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Liao
authors.affiliation: State Key Laboratory of Agrobiotechnology, China Agricultural University, Beijing 100193, China; College of Veterinary Medicine, China Agricultural University, Beijing 100193, China. Electronic address: jtang@cau.edu.cn.
authors.forename: Jun
authors.initials: J
authors.lastname: Tang
mesh_terms: D001354:Avian Leukosis Virus / Q000201:enzymology* / Q000502:physiology; D001483:Base Sequence; D000075686:COP9 Signalosome Complex; D020134:Catalytic Domain; D017931:DNA Primers; D057809:HEK293 Cells; D006801:Humans; D019426:Integrases / Q000378:metabolism*; D046912:Multiprotein Complexes / Q000378:metabolism*; D010447:Peptide Hydrolases / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D011485:Protein Binding; D014779:Virus Replication
chemical_list: D017931:DNA Primers; D046912:Multiprotein Complexes; D019426:Integrases; D010447:Peptide Hydrolases; D000075686:COP9 Signalosome Complex
keywords: Avian leukosis virus; COP9 signalosome subunit 6; Integrase; Retrovirus