Species-specific host factors rather than virus-intrinsic virulence determine primate lentiviral pathogenicity

Simone Joas, Erica H. Parrish, Clement W. Gnanadurai, Edina Lump, Christina M. Stürzel, Nicholas F. Parrish, Gerald H. Learn, Ulrike Sauermann, Berit Neumann, Kerstin Mätz Rensing, Dietmar Fuchs, James M. Billingsley, Steven E. Bosinger, Guido Silvestri, Cristian Apetrei, Nicolas Huot, Thalia Garcia-Tellez, Michaela Müller-Trutwin, Dominik Hotter, Daniel Sauter, Christiane Stahl-Hennig, Beatrice H. Hahn and Frank Kirchhoff ()
Additional contact information
Simone Joas: Ulm University Medical Center
Erica H. Parrish: University of Pennsylvania
Clement W. Gnanadurai: Ulm University Medical Center
Edina Lump: Ulm University Medical Center
Christina M. Stürzel: Ulm University Medical Center
Nicholas F. Parrish: University of Pennsylvania
Gerald H. Learn: University of Pennsylvania
Ulrike Sauermann: German Primate Centre
Berit Neumann: German Primate Centre
Kerstin Mätz Rensing: German Primate Centre
Dietmar Fuchs: Biocenter Innsbruck Medical University, Center for Chemistry and Biomedicine
James M. Billingsley: Emory University
Steven E. Bosinger: Emory University
Guido Silvestri: Emory University
Cristian Apetrei: University of Pittsburgh
Nicolas Huot: Inflammation and Persistence
Thalia Garcia-Tellez: Inflammation and Persistence
Michaela Müller-Trutwin: Inflammation and Persistence
Dominik Hotter: Ulm University Medical Center
Daniel Sauter: Ulm University Medical Center
Christiane Stahl-Hennig: German Primate Centre
Beatrice H. Hahn: University of Pennsylvania
Frank Kirchhoff: Ulm University Medical Center

Nature Communications, 2018, vol. 9, issue 1, 1-16

Abstract: Abstract HIV-1 causes chronic inflammation and AIDS in humans, whereas related simian immunodeficiency viruses (SIVs) replicate efficiently in their natural hosts without causing disease. It is currently unknown to what extent virus-specific properties are responsible for these different clinical outcomes. Here, we incorporate two putative HIV-1 virulence determinants, i.e., a Vpu protein that antagonizes tetherin and blocks NF-κB activation and a Nef protein that fails to suppress T cell activation via downmodulation of CD3, into a non-pathogenic SIVagm strain and test their impact on viral replication and pathogenicity in African green monkeys. Despite sustained high-level viremia over more than 4 years, moderately increased immune activation and transcriptional signatures of inflammation, the HIV-1-like SIVagm does not cause immunodeficiency or any other disease. These data indicate that species-specific host factors rather than intrinsic viral virulence factors determine the pathogenicity of primate lentiviruses.

Date: 2018
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DOI: 10.1038/s41467-018-03762-3

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