[HTML][HTML] Gene therapy with plasmids encoding IFN-β or IFN-α14 confers long-term resistance to HIV-1 in humanized mice

S Abraham, JG Choi, NM Ortega, J Zhang, P Shankar… - Oncotarget, 2016 - ncbi.nlm.nih.gov
S Abraham, JG Choi, NM Ortega, J Zhang, P Shankar, NM Swamy
Oncotarget, 2016ncbi.nlm.nih.gov
Because endogenous interferon type I (IFN-I) produced by HIV-1 infection might complicate
the analysis of therapeutically administered IFN-I, we tested different humanized mouse
models for induction of IFN-I during HIV-1 infection. While HIV-1 induced high levels of IFN-α
in BLT mice, IFN-I was undetectable following infection in the Hu-PBL mouse model, in
which only T cells expand. We therefore tested the effect of treatment with Pegylated IFN-2
(pegasys), in Hu-PBL mice. Pegasys prevented CD4 T cell depletion and reduced the viral …
Abstract
Because endogenous interferon type I (IFN-I) produced by HIV-1 infection might complicate the analysis of therapeutically administered IFN-I, we tested different humanized mouse models for induction of IFN-I during HIV-1 infection. While HIV-1 induced high levels of IFN-α in BLT mice, IFN-I was undetectable following infection in the Hu-PBL mouse model, in which only T cells expand. We therefore tested the effect of treatment with Pegylated IFN-2 (pegasys), in Hu-PBL mice. Pegasys prevented CD4 T cell depletion and reduced the viral load for 10 days, but the effect waned thereafter. We next expressed IFN-I subsets (IFN-α2,− α6,− α8,− α14, and− β) in Hu-PBL mice by hydrodynamic injection of plasmids encoding them and 2 days later infected the mice with HIV-1. CD4 T cell depletion was prevented in all subtypes of IFN-I-expressing mice by day 10. However, at day 40 post-infection, protection was seen in IFN-β-and IFN-α14-expressing mice, but not the others. The viral load followed an inverse pattern and was highest in control mice and lowest in IFN-β-and IFN-α14-expressing mice until day 40 after infection. These results show that gene therapy with plasmids encoding IFN-β and− α14, but not the commonly used− α2, confers long-term suppression of HIV-1 replication.
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