Intracellular expression of antisense RNA transcripts complementary to the human immunodeficiency virus type-1 vif gene inhibits viral replication in infected T-lymphoblastoid cells.
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.
Barnor
Jacob Samson
JS
Department of Life and Environmental Science, 2-17-1 Tsudanuma, 275-0016 Narashino, Chiba, Japan.
Miyano-Kurosaki
Naoko
N
Yamaguchi
Kazuya
K
Sakamoto
Atsushi
A
Ishikawa
Koichi
K
Inagaki
Yoshio
Y
Yamamoto
Naoki
N
Osei-Kwasi
Mubarak
M
Ofori-Adjei
David
D
Takaku
Hiroshi
H
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*
D017931:DNA Primers; D016372:RNA, Antisense; D012333:RNA, Messenger