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′-Δvif; 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 t...