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

Simone Joas (1) , Erica H Parrish (2) , Clement W Gnanadurai (1) , Edina Lump (1) , Christina M Stürzel (1) , Nicholas F Parrish (2) , Gerald H Learn (2) , Ulrike Sauermann (3) , Berit Neumann (3) , Kerstin Mätz Rensing (3) , Dietmar Fuchs (4) , James M Billingsley (5) , Steven E 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 - HIV, Inflammation and Persistence
8 VRI - Vaccine Research Institute

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.

Domains: Life Sciences [q-bio]; Human health and pathology; Infectious diseases; Life Sciences [q-bio]; Microbiology and Parasitology; Virology; Life Sciences [q-bio]; Immunology; Life Sciences [q-bio]; Animal biology

Simone Joas, Erica H Parrish, Clement W Gnanadurai, Edina Lump, Christina M Stürzel, et al.. Species-specific host factors rather than virus-intrinsic virulence determine primate lentiviral pathogenicity. Nature Communications, 2018, 9 (1), pp.1371 - 1371. ⟨10.1038/s41467-018-03762-3⟩. ⟨pasteur-01959320⟩