Oncotarget

Research Papers: Immunology:

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

Sojan Abraham, Jang-Gi Choi, Nora M. Ortega, Junli Zhang, Premlata Shankar and N. Manjunath Swamy _

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Oncotarget. 2016; 7:78412-78420. https://doi.org/10.18632/oncotarget.12512

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Abstract

Sojan Abraham1, Jang-Gi Choi1,2, Nora M. Ortega1, Junli Zhang1, Premlata Shankar1 and N. Manjunath Swamy1

1 Center of Emphasis in Infectious Disease, Department of Biomedical Sciences, Paul L. Foster School of Medicine, Texas Tech University Health Sciences Center, El Paso, TX, USA

2 KM Application Center, Korea Institute of Oriental Medicine, Dong-gu, Daegu, Republic of Korea

Correspondence to:

N. Manjunath Swamy, email:

Keywords: interferon, HIV-1, hydrodynamic injection, Immunology and Microbiology Section, Immune response, Immunity

Received: May 20, 2016 Accepted: October 02, 2016 Published: October 06, 2016

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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