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

Simone Joas 1 Erica Parrish 2 Clement Gnanadurai 1 Edina Lump 1 Christina Stürzel 1 Nicholas Parrish 2 Gerald Learn 2 Ulrike Sauermann 3 Berit Neumann 3 Kerstin Mätz Rensing 3 Dietmar Fuchs 4 James Billingsley 5 Steven Bosinger 5 Guido Silvestri 5 Cristian Apetrei 6 Nicolas Huot 7, 8 Thalía Garcia-Tellez 7 Michaela Muller-Trutwin 7 Dominik Hotter 1 Daniel Sauter 1 Christiane Stahl-Hennig 3 Beatrice Hahn 2 Frank Kirchhoff 1
1 Universität Ulm - Ulm University [Ulm, Allemagne]
2 University of Pennsylvania [Philadelphia]
3 German Primate Centre
4 IMU - Innsbruck Medical University [Austria]
5 Emory University [Atlanta, GA]
6 PITT - University of Pittsburgh
7 HIV, Inflammation et persistance
8 VRI - Vaccine Research Institute
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.
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Simone Joas, Erica Parrish, Clement Gnanadurai, Edina Lump, Christina Stürzel, et al.. Species-specific host factors rather than virus-intrinsic virulence determine primate lentiviral pathogenicity. Nature Communications, Nature Publishing Group, 2018, 9 (1), pp.1371 - 1371. ⟨10.1038/s41467-018-03762-3⟩. ⟨pasteur-01959320⟩

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