Inhibitory function of adapter-related protein complex 2 alpha 1 subunit in the process of nuclear translocation of human immunodeficiency virus type 1 genome.
The transfection of human cells with siRNA against adapter-related protein complex 2 alpha 1 subunit (AP2alpha) 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 AP2alpha. In contrast, viral nuclear translocation as well as the integration process was significantly up-regulated in cells transfected with siRNA against AP2alpha. Confocal fluorescence microscopy revealed that a subpopulation of AP2alpha was not only localized in the cytoplasm but was also partly co-localized with lamin B, importin beta and Nup153, implying that AP2alpha negatively regulates HIV-1 replication in the process of nuclear translocation of viral DNA in the cytoplasm or the perinuclear region. We propose that AP2alpha may be a novel target for disrupting HIV-1 replication in the early stage of the viral life cycle.
Kitagawa
Yukiko
Y
Department of Virology, Research Institute for Microbial Diseases and Osaka University, Osaka 565-0871, Japan.
Kameoka
Masanori
M
Shoji-Kawata
Sanae
S
Iwabu
Yukie
Y
Mizuta
Hiroyuki
H
Tokunaga
Kenzo
K
Fujino
Masato
M
Natori
Yukikazu
Y
Yura
Yoshiaki
Y
Ikuta
Kazuyoshi
K
D021581:Active Transport, Cell Nucleus; D033962:Adaptor Protein Complex 2 / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism* / Q000821:virology*; D003593:Cytoplasm / Q000378:metabolism; D004279:DNA, Viral / Q000378:metabolism; D015497:HIV-1 / Q000235:genetics / Q000472:pathogenicity* / Q000502:physiology; D006801:Humans; D008562:Membrane Glycoproteins; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D014759:Viral Envelope Proteins; D016662:Virus Integration; D014779:Virus Replication
D033962:Adaptor Protein Complex 2; D004279:DNA, Viral; C028391:G protein, vesicular stomatitis virus; D008562:Membrane Glycoproteins; D034741:RNA, Small Interfering; D014759:Viral Envelope Proteins