Vpr attenuates antiviral immune responses and is critical for full pathogenicity of SIVmac239 in rhesus macaques
Summary: 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...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2023-12-01
|
| Series: | iScience |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004223024288 |
| _version_ | 1797388773921652736 |
|---|---|
| author | 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 |
| author_facet | 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 |
| author_sort | Alexandre Laliberté |
| collection | DOAJ |
| description | Summary: 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 SIVmac239 in rhesus macaques. All wild-type SIVmac239-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 SIVmac in vivo. Inhibition of Vpr may improve humoral immune control of viral replication. |
| first_indexed | 2024-03-08T22:45:41Z |
| format | Article |
| id | doaj.art-d97b01ec79264fde9d35d16bbbf8793a |
| institution | Directory Open Access Journal |
| issn | 2589-0042 |
| language | English |
| last_indexed | 2024-03-08T22:45:41Z |
| publishDate | 2023-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj.art-d97b01ec79264fde9d35d16bbbf8793a2023-12-17T06:40:28ZengElsevieriScience2589-00422023-12-012612108351Vpr attenuates antiviral immune responses and is critical for full pathogenicity of SIVmac239 in rhesus macaquesAlexandre Laliberté0Caterina Prelli Bozzo1Christiane Stahl-Hennig2Victoria Hunszinger3Simone Joas4Ulrike Sauermann5Berit Roshani6Antonina Klippert7Maria Daskalaki8Kerstin Mätz-Rensing9Nicole Stolte-Leeb10Gregory K. Tharp11Dietmar Fuchs12Prachi Mehrotra Gupta13Guido Silvestri14Sydney A. Nelson15Laura Parodi16Luis Giavedoni17Steven E. Bosinger18Konstantin M.J. Sparrer19Frank Kirchhoff20Institute of Molecular Virology – Ulm University Medical Center, Meyerhofstraße 1, 89081 Ulm, GermanyInstitute of Molecular Virology – Ulm University Medical Center, Meyerhofstraße 1, 89081 Ulm, GermanyGerman Primate Center, Kellnerweg 4, 37077 Göttingen, GermanyInstitute of Molecular Virology – Ulm University Medical Center, Meyerhofstraße 1, 89081 Ulm, GermanyInstitute of Molecular Virology – Ulm University Medical Center, Meyerhofstraße 1, 89081 Ulm, GermanyGerman Primate Center, Kellnerweg 4, 37077 Göttingen, GermanyGerman Primate Center, Kellnerweg 4, 37077 Göttingen, GermanyGerman Primate Center, Kellnerweg 4, 37077 Göttingen, GermanyGerman Primate Center, Kellnerweg 4, 37077 Göttingen, GermanyGerman Primate Center, Kellnerweg 4, 37077 Göttingen, GermanyGerman Primate Center, Kellnerweg 4, 37077 Göttingen, GermanyEmory National Primate Research Center, Emory Vaccine Center and Department of Pathology & Laboratory Medicine, Emory University, Atlanta, GA, USAGerman Primate Center, Kellnerweg 4, 37077 Göttingen, GermanyEmory National Primate Research Center, Emory Vaccine Center and Department of Pathology & Laboratory Medicine, Emory University, Atlanta, GA, USAEmory National Primate Research Center, Emory Vaccine Center and Department of Pathology & Laboratory Medicine, Emory University, Atlanta, GA, USAEmory National Primate Research Center, Emory Vaccine Center and Department of Pathology & Laboratory Medicine, Emory University, Atlanta, GA, USAHost-Pathogen Interactions Program, Southwest National Primate Research Center, Texas Biomedical Research Institute, San Antonio, TX, USAHost-Pathogen Interactions Program, Southwest National Primate Research Center, Texas Biomedical Research Institute, San Antonio, TX, USAEmory National Primate Research Center, Emory Vaccine Center and Department of Pathology & Laboratory Medicine, Emory University, Atlanta, GA, USAInstitute of Molecular Virology – Ulm University Medical Center, Meyerhofstraße 1, 89081 Ulm, GermanyInstitute of Molecular Virology – Ulm University Medical Center, Meyerhofstraße 1, 89081 Ulm, Germany; Corresponding authorSummary: 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 SIVmac239 in rhesus macaques. All wild-type SIVmac239-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 SIVmac in vivo. Inhibition of Vpr may improve humoral immune control of viral replication.http://www.sciencedirect.com/science/article/pii/S2589004223024288ImmunologyImmunityImmune response |
| spellingShingle | 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 Vpr attenuates antiviral immune responses and is critical for full pathogenicity of SIVmac239 in rhesus macaques iScience Immunology Immunity Immune response |
| title | Vpr attenuates antiviral immune responses and is critical for full pathogenicity of SIVmac239 in rhesus macaques |
| title_full | Vpr attenuates antiviral immune responses and is critical for full pathogenicity of SIVmac239 in rhesus macaques |
| title_fullStr | Vpr attenuates antiviral immune responses and is critical for full pathogenicity of SIVmac239 in rhesus macaques |
| title_full_unstemmed | Vpr attenuates antiviral immune responses and is critical for full pathogenicity of SIVmac239 in rhesus macaques |
| title_short | Vpr attenuates antiviral immune responses and is critical for full pathogenicity of SIVmac239 in rhesus macaques |
| title_sort | vpr attenuates antiviral immune responses and is critical for full pathogenicity of sivmac239 in rhesus macaques |
| topic | Immunology Immunity Immune response |
| url | http://www.sciencedirect.com/science/article/pii/S2589004223024288 |
| work_keys_str_mv | AT alexandrelaliberte vprattenuatesantiviralimmuneresponsesandiscriticalforfullpathogenicityofsivmac239inrhesusmacaques AT caterinaprellibozzo vprattenuatesantiviralimmuneresponsesandiscriticalforfullpathogenicityofsivmac239inrhesusmacaques AT christianestahlhennig vprattenuatesantiviralimmuneresponsesandiscriticalforfullpathogenicityofsivmac239inrhesusmacaques AT victoriahunszinger vprattenuatesantiviralimmuneresponsesandiscriticalforfullpathogenicityofsivmac239inrhesusmacaques AT simonejoas vprattenuatesantiviralimmuneresponsesandiscriticalforfullpathogenicityofsivmac239inrhesusmacaques AT ulrikesauermann vprattenuatesantiviralimmuneresponsesandiscriticalforfullpathogenicityofsivmac239inrhesusmacaques AT beritroshani vprattenuatesantiviralimmuneresponsesandiscriticalforfullpathogenicityofsivmac239inrhesusmacaques AT antoninaklippert vprattenuatesantiviralimmuneresponsesandiscriticalforfullpathogenicityofsivmac239inrhesusmacaques AT mariadaskalaki vprattenuatesantiviralimmuneresponsesandiscriticalforfullpathogenicityofsivmac239inrhesusmacaques AT kerstinmatzrensing vprattenuatesantiviralimmuneresponsesandiscriticalforfullpathogenicityofsivmac239inrhesusmacaques AT nicolestolteleeb vprattenuatesantiviralimmuneresponsesandiscriticalforfullpathogenicityofsivmac239inrhesusmacaques AT gregoryktharp vprattenuatesantiviralimmuneresponsesandiscriticalforfullpathogenicityofsivmac239inrhesusmacaques AT dietmarfuchs vprattenuatesantiviralimmuneresponsesandiscriticalforfullpathogenicityofsivmac239inrhesusmacaques AT prachimehrotragupta vprattenuatesantiviralimmuneresponsesandiscriticalforfullpathogenicityofsivmac239inrhesusmacaques AT guidosilvestri vprattenuatesantiviralimmuneresponsesandiscriticalforfullpathogenicityofsivmac239inrhesusmacaques AT sydneyanelson vprattenuatesantiviralimmuneresponsesandiscriticalforfullpathogenicityofsivmac239inrhesusmacaques AT lauraparodi vprattenuatesantiviralimmuneresponsesandiscriticalforfullpathogenicityofsivmac239inrhesusmacaques AT luisgiavedoni vprattenuatesantiviralimmuneresponsesandiscriticalforfullpathogenicityofsivmac239inrhesusmacaques AT stevenebosinger vprattenuatesantiviralimmuneresponsesandiscriticalforfullpathogenicityofsivmac239inrhesusmacaques AT konstantinmjsparrer vprattenuatesantiviralimmuneresponsesandiscriticalforfullpathogenicityofsivmac239inrhesusmacaques AT frankkirchhoff vprattenuatesantiviralimmuneresponsesandiscriticalforfullpathogenicityofsivmac239inrhesusmacaques |