title: Gene therapy with plasmids encoding IFN-β or IFN-α14 confers long-term resistance to HIV-1 in humanized mice.
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.
authors.affiliation: 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.
authors.forename: Sojan
authors.initials: S
authors.lastname: Abraham
authors.affiliation: 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.|KM Application Center, Korea Institute of Oriental Medicine, Dong-gu, Daegu, Republic of Korea.
authors.forename: Jang-Gi
authors.initials: JG
authors.lastname: Choi
authors.affiliation: 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.
authors.forename: Nora M
authors.initials: NM
authors.lastname: Ortega
authors.affiliation: 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.
authors.forename: Junli
authors.initials: J
authors.lastname: Zhang
authors.affiliation: 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.
authors.forename: Premlata
authors.initials: P
authors.lastname: Shankar
authors.affiliation: 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.
authors.forename: N Manjunath
authors.initials: NM
authors.lastname: Swamy
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology; D004195:Disease Models, Animal; D015316:Genetic Therapy / Q000379:methods*; D015658:HIV Infections / Q000235:genetics / Q000276:immunology / Q000517:prevention & control* / Q000821:virology; D015497:HIV-1 / Q000187:drug effects / Q000254:growth & development / Q000276:immunology*; D006801:Humans; D016898:Interferon-alpha / Q000096:biosynthesis / Q000235:genetics* / Q000276:immunology / Q000494:pharmacology; D016899:Interferon-beta / Q000096:biosynthesis / Q000235:genetics* / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000637:transplantation*; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D011092:Polyethylene Glycols / Q000494:pharmacology; D011994:Recombinant Proteins / Q000494:pharmacology; D013997:Time Factors; D019562:Viral Load; D014779:Virus Replication
chemical_list: D000998:Antiviral Agents; C554325:IFNA14 protein, human; C554158:IFNA2 protein, human; D016898:Interferon-alpha; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D016899:Interferon-beta; C100416:peginterferon alfa-2a
keywords: HIV-1; Immune response; Immunity; Immunology and Microbiology Section; hydrodynamic injection; interferon