title: Intracellular expression of antisense RNA transcripts complementary to the human immunodeficiency virus type-1 vif gene inhibits viral replication in infected T-lymphoblastoid cells.
abstract: The human immunodeficiency virus type-1 (HIV-1)-encoded vif protein is essential for viral replication, virion production, and pathogenicity. HIV-1 vif interacts with the endogenous human APOBEC3G protein (an mRNA editor) in target cells to prevent its virions from encapsidation. Although some studies have established targets within the HIV-1 vif gene that are important for its biologic function, it is however important to further screen for effective therapeutic targets in the vif gene that could interfere with the HIV-1 vif-dependent infectivity and pathogenicity. This report demonstrates that HIV-1 vif antisense RNA fragments constructed within mid-3' region, notably the region spanning nucleic acid positions 5561-5705 (M-3'-AS), significantly inhibited HIV-1 replication in MT-4 and H9-infected cells and reduced the HIV-1 vif mRNA transcripts. These data clearly suggest that the above vif fragment, which corresponds to amino acid residues 96-144, could be an effective novel therapeutic target site for gene therapy applications, for the control and management of HIV-1 infection, due to its strong inhibition of HIV-1 replication in cells.
authors.affiliation: Department of Life and Environmental Science, 2-17-1 Tsudanuma, 275-0016 Narashino, Chiba, Japan.
authors.forename: Jacob Samson
authors.initials: JS
authors.lastname: Barnor
authors.forename: Naoko
authors.initials: N
authors.lastname: Miyano-Kurosaki
authors.forename: Kazuya
authors.initials: K
authors.lastname: Yamaguchi
authors.forename: Atsushi
authors.initials: A
authors.lastname: Sakamoto
authors.forename: Koichi
authors.initials: K
authors.lastname: Ishikawa
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Inagaki
authors.forename: Naoki
authors.initials: N
authors.lastname: Yamamoto
authors.forename: Mubarak
authors.initials: M
authors.lastname: Osei-Kwasi
authors.forename: David
authors.initials: D
authors.lastname: Ofori-Adjei
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Takaku
mesh_terms: D001483:Base Sequence; D002460:Cell Line; D017931:DNA Primers; D015536:Down-Regulation; D016341:Genes, vif; D015497:HIV-1 / Q000235:genetics* / Q000502:physiology; D006801:Humans; D016372:RNA, Antisense / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics*; D013601:T-Lymphocytes / Q000821:virology*; D014779:Virus Replication / Q000235:genetics*
chemical_list: D017931:DNA Primers; D016372:RNA, Antisense; D012333:RNA, Messenger