The middle to 3' end of the HIV-1 vif gene sequence is important for vif biological activity and could be used for antisense oligonucleotide targets.
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 encapsidation into virions. Some studies have established targets within the HIV-1 vif gene that are important for its biologic function; however, it is important to determine effective therapeutic targets in vif because of its critical role in HIV-1 infectivity and pathogenicity. The present study demonstrates that virions generated in transfected HeLa-CD4+ cells, especially from HIV-1 vif frame-shift mutant (3' delta vif; 5561-5849), were affected in splicing and had low infectivity in MT-4 cells. In addition, HIV-1 vif antisense RNA fragments constructed within the same region, notably the region spanning nucleic acid positions 5561-5705 (M-3'-AS), which corresponds to amino acid residues 96-144, significantly inhibited HIV-1 replication in MT-4 and reduced the HIV-1 vif mRNA transcripts and reporter gene (EGFP) expression. The generated virions showed low secondary infection in H9 cells. These data therefore suggest that the middle to the 3' end of vif is important for its biological activity in the target cells.
Barnor
Jacob Samson
JS
Department of Life and Environmental Science, Chiba Institute of Technology, Tsudanuma, Narashino, Chiba, Japan.
Miyano-Kurosaki
Naoko
N
Takaku
Hiroshi
H
Yamaguchi
Kazuya
K
Sakamoto
Atsushi
A
Ishikawa
Koichi
K
Yamamoto
Naoki
N
Osei-Kwasi
Mubarak
M
Ofori-Adjei
David
D
D024509:3' Flanking Region; D000818:Animals; D019556:COS Cells; D002522:Chlorocebus aethiops; D016346:Gene Products, vif / Q000235:genetics*; D005822:Genetic Vectors; D015497:HIV-1 / Q000235:genetics* / Q000254:growth & development; D006367:HeLa Cells; D006801:Humans; D016372:RNA, Antisense / Q000235:genetics*; D014779:Virus Replication / Q000235:genetics*; D054320:vif Gene Products, Human Immunodeficiency Virus
D016346:Gene Products, vif; D016372:RNA, Antisense; D054320:vif Gene Products, Human Immunodeficiency Virus