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Vpr attenuates antiviral immune responses and is critical for full pathogenicity of SIV mac239 in rhesus macaques.
- Source :
-
IScience [iScience] 2023 Oct 26; Vol. 26 (12), pp. 108351. Date of Electronic Publication: 2023 Oct 26 (Print Publication: 2023). - Publication Year :
- 2023
-
Abstract
- The accessory viral protein R (Vpr) is encoded by all primate lentiviruses. Vpr counteracts DNA repair pathways, modulates viral immune sensing, and induces cell-cycle arrest in cell culture. However, its impact in vivo is controversial. Here, we show that deletion of vpr is associated with delayed viral replication kinetics, rapid innate immune activation, development and maintenance of strong B and T cell responses, and increased neutralizing activity against SIV <subscript>mac239</subscript> in rhesus macaques. All wild-type SIV <subscript>mac239</subscript> -infected animals maintained high viral loads, and five of six developed fatal immunodeficiency during ∼80 weeks of follow-up. Lack of Vpr was associated with better preservation of CD4 <superscript>+</superscript> T cells, lower viral loads, and an attenuated clinical course of infection in most animals. Our results show that Vpr contributes to efficient viral immune evasion and the full pathogenic potential of SIV <subscript>mac</subscript> in vivo . Inhibition of Vpr may improve humoral immune control of viral replication.<br />Competing Interests: The authors declare no competing interests.<br /> (© 2023 The Author(s).)
Details
- Language :
- English
- ISSN :
- 2589-0042
- Volume :
- 26
- Issue :
- 12
- Database :
- MEDLINE
- Journal :
- IScience
- Publication Type :
- Academic Journal
- Accession number :
- 38025783
- Full Text :
- https://doi.org/10.1016/j.isci.2023.108351