Functional Neutralization of HIV-1 Vif Protein by Intracellular Immunization Inhibits Reverse Transcription and Viral Replication

Gene therapy progress and prospects: Novel gene therapy approaches for AIDS

“…Another way to interfere with Vif function is to create and express a Vifspecific single-chain antibody (scFv) in the cytoplasm of T cells. 24 In this study, the intrabody was capable of binding Vif and cells expressing the a-Vif intrabody were more resistant to infection by several strains of HIV-1 than were cells without the intrabody. Moreover, the viral particles produced by intrabody-expressing cells were not able to complete reverse transcription in subsequently infected cells.…”

“…Finally, peripheral blood mononuclear cells (PBMC) transduced with HIV-1-based vectors carrying the a-Vif intrabody were resistant to laboratory-adapted and primary HIV strains. 24 In another example, retroviral plasmid-based delivery was used to express intrabodies to the a-HIV-1 Gag p17 protein in the cytoplasm of primary human T cells and in Jurkat cells (a human CD4(+) T cell line). 25 When these cells were challenged with several strains of HIV-1, replication was strongly inhibited, although the degree of resistance varied and was not efficient in cells that sustained high viral replication.…”

Gene Therapy for HIV-1 Infection

“…Antibodies can be expressed within gene-modified cells as single-chain fragments (scFv), so-called intrabodies, or they can be secreted into the supernatant as neutralizing antibodies. Various intrabodies against HIV-1 proteins including Tat, Vif, Reverse Transcriptase and Integrase have been shown to inhibit virus replication in gene-modified cells in vitro (Goncalves et al, 2002;Kitamura et al, 1999;Levy-Mintz et al, 1996;Mhashilkar et al, 1995;Shaheen et al, 1996). Moreover, intrabodies against the viral co-receptors CXCR4 and CCR5 have been designed that retain these proteins in the ER (BouHamdan et al, 2001;Cordelier et al, 2004;Swan et al, 2006).…”

Advantages and Disadvantages of Cytidine Deamination

“…Cytidine deamination of retroviral cDNA by APOBEC3G is suppressed by a Vif produced by the HIV (57,58). Vif impairs both the translation and the stability of APOBEC3G mRNA and promotes the degradation of APOBEC3G by the 26S proteosome, depleting APOBEC3G from cells, thus blocking antiviral activity of APOBEC3G (40, 59 -62).…”