Vpr attenuates antiviral immune responses and is critical for full pathogenicity of SIVmac239 in rhesus macaques

Alexandre Laliberté; Caterina Prelli Bozzo; Christiane Stahl-Hennig; Victoria Hunszinger; Simone Joas; Ulrike Sauermann; Berit Roshani; Antonina Klippert; Maria Daskalaki; Kerstin Mätz-Rensing; Nicole Stolte-Leeb; Gregory K Tharp; Dietmar Fuchs; Prachi Mehrotra Gupta; Guido Silvestri; Sydney A Nelson; Laura Parodi; Luis Giavedoni; Steven E Bosinger; Konstantin M J Sparrer; Frank Kirchhoff

doi:10.1016/j.isci.2023.108351

Vpr attenuates antiviral immune responses and is critical for full pathogenicity of SIV_mac239 in rhesus macaques

iScience. 2023 Oct 26;26(12):108351. doi: 10.1016/j.isci.2023.108351. eCollection 2023 Dec 15.

Authors

Alexandre Laliberté¹, Caterina Prelli Bozzo¹, Christiane Stahl-Hennig², Victoria Hunszinger¹, Simone Joas¹, Ulrike Sauermann², Berit Roshani², Antonina Klippert², Maria Daskalaki², Kerstin Mätz-Rensing², Nicole Stolte-Leeb², Gregory K Tharp³, Dietmar Fuchs², Prachi Mehrotra Gupta³, Guido Silvestri³, Sydney A Nelson³, Laura Parodi⁴, Luis Giavedoni⁴, Steven E Bosinger³, Konstantin M J Sparrer¹, Frank Kirchhoff¹

Affiliations

¹ Institute of Molecular Virology - Ulm University Medical Center, Meyerhofstraße 1, 89081 Ulm, Germany.
² German Primate Center, Kellnerweg 4, 37077 Göttingen, Germany.
³ Emory National Primate Research Center, Emory Vaccine Center and Department of Pathology & Laboratory Medicine, Emory University, Atlanta, GA, USA.
⁴ Host-Pathogen Interactions Program, Southwest National Primate Research Center, Texas Biomedical Research Institute, San Antonio, TX, USA.

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_mac239 in rhesus macaques. All wild-type SIV_mac239-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⁺ 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_macin vivo. Inhibition of Vpr may improve humoral immune control of viral replication.

Keywords: Immune response; Immunity; Immunology.

Abstract

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