Inhibitory function of adapter-related protein complex 2 alpha 1 subunit in the process of nuclear translocation of human immunodeficiency virus type 1 genome

• Published in: Virology (New York, N.Y.) N.Y.), 2008-03, Vol.373 (1), p.171-180
• Main Authors: Kitagawa, Yukiko, Kameoka, Masanori, Shoji-Kawata, Sanae, Iwabu, Yukie, Mizuta, Hiroyuki, Tokunaga, Kenzo, Fujino, Masato, Natori, Yukikazu, Yura, Yoshiaki, Ikuta, Kazuyoshi
• Format: Article
• Language: English
• Subjects: 60 APPLIED LIFE SCIENCES; Active Transport, Cell Nucleus; Adapter-related protein complex 2 alpha 1 subunit; Adaptor Protein Complex 2 - genetics; Adaptor Protein Complex 2 - metabolism; ADSORPTION; AIDS; AIDS VIRUS; ANIMAL CELLS; AP-2; Cell Line; Cell Nucleus - metabolism; Cell Nucleus - virology; CYTOPLASM; Cytoplasm - metabolism; DNA; DNA, Viral - metabolism; FLUORESCENCE; GTP-ASES; HIV-1; HIV-1 - genetics; HIV-1 - pathogenicity; HIV-1 - physiology; Host factor; Human immunodeficiency virus 1; Human immunodeficiency virus 2; Humans; Infectious Disease; Integration; LIFE CYCLE; Membrane Glycoproteins; MICROSCOPY; Nuclear translocation; RNA; RNA Interference; RNA, Small Interfering - genetics; RNA, Small Interfering - metabolism; siRNA; TRANSCRIPTION; TRANSLOCATION; Vesicular stomatitis virus; Viral Envelope Proteins; Virus Integration; Virus Replication
• ISSN: 0042-6822; 1096-0341
• DOI: 10.1016/j.virol.2007.11.033

Abstract The transfection of human cells with siRNA against adapter-related protein complex 2 alpha 1 subunit (AP2α) was revealed to significantly up-regulate the replication of human immunodeficiency virus type 1 (HIV-1). This effect was confirmed by cell infection with vesicular stomatitis virus G protein-pseudotyped HIV-1 as well as CXCR4-tropic and CCR5-tropic HIV-1. Viral adsorption, viral entry and reverse transcription processes were not affected by cell transfection with siRNA against AP2α. In contrast, viral nuclear translocation as well as the integration process was significantly up-regulated in cells transfected with siRNA against AP2α. Confocal fluorescence microscopy revealed that a subpopulation of AP2α was not only localized in the cytoplasm but was also partly co-localized with lamin B, importin β and Nup153, implying that AP2α negatively regulates HIV-1 replication in the process of nuclear translocation of viral DNA in the cytoplasm or the perinuclear region. We propose that AP2α may be a novel target for disrupting HIV-1 replication in the early stage of the viral life cycle.