title: Role of Nup98 in nuclear entry of human immunodeficiency virus type 1 cDNA.
abstract: Human immunodeficiency virus type 1 (HIV-1), like other lentiviruses, can infect non-dividing cells. The lentiviruses are most likely to have evolved a nuclear import strategy to import HIV-1 cDNA and viral protein complex through the nuclear pore complex (NPC) formed by nucleoporin proteins (Nup). In this study, we found that synthesis of integrated and 2LTR but not full-length form of HIV-1 cDNA was clearly impaired in culture via transduction of vesicular stomatitis virus matrix protein (VSV M), an inhibitor protein, through binding to the phenylalanine-glycine (FG) repeat region of Nup98. The impairment of synthesis of integrated and 2LTR DNA with VSV M was restored by ectopic overexpression of Nup98. A series of experiments using Nup98-depleted NPC by the small interfering RNA (siRNA) technique showed specific impairment of NPC structure and some functions, including nuclear import of HIV-1 cDNA. Our results suggest that Nup98 on the NPC specifically participates in the nuclear entry of HIV-1 cDNA following HIV-1 entry.
authors.affiliation: Department of Virology, Tohoku University Graduate School of Medicine, Sendai 980-8575, Japan.
authors.forename: Hirotaka
authors.initials: H
authors.lastname: Ebina
authors.forename: Jun
authors.initials: J
authors.lastname: Aoki
authors.forename: Shunsuke
authors.initials: S
authors.lastname: Hatta
authors.forename: Takeshi
authors.initials: T
authors.lastname: Yoshida
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Koyanagi
mesh_terms: D021581:Active Transport, Cell Nucleus; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism / Q000821:virology*; D018076:DNA, Complementary / Q000378:metabolism*; D004279:DNA, Viral / Q000378:metabolism*; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D022022:Nuclear Pore / Q000821:virology; D028861:Nuclear Pore Complex Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D014763:Viral Matrix Proteins / Q000235:genetics / Q000378:metabolism; D016662:Virus Integration
chemical_list: D018076:DNA, Complementary; D004279:DNA, Viral; C094460:M protein, Vesicular stomatitis virus; D028861:Nuclear Pore Complex Proteins; C465451:Nup98 protein, human; D034741:RNA, Small Interfering; D014763:Viral Matrix Proteins