James M. Billingsley, Erica H. Parrish, Frank Kirchhoff, Thalia Garcia-Tellez, Nicolas Huot, Guido Silvestri, Ulrike Sauermann, Berit Neumann, Christina M. Stürzel, Gerald H. Learn, Steven E. Bosinger, Christiane Stahl-Hennig, Daniel Sauter, Beatrice H. Hahn, Dietmar Fuchs, Clement W. Gnanadurai, Michaela Müller-Trutwin, Simone Joas, Dominik Hotter, Edina Lump, Cristian Apetrei, Nicholas F. Parrish, Kerstin Mätz Rensing, Universität Ulm - Ulm University [Ulm, Allemagne], University of Pennsylvania, German Primate Centre, Innsbruck Medical University = Medizinische Universität Innsbruck (IMU), Emory University [Atlanta, GA], University of Pittsburgh (PITT), Pennsylvania Commonwealth System of Higher Education (PCSHE), HIV, Inflammation et persistance - HIV, Inflammation and Persistence, Institut Pasteur [Paris] (IP), Vaccine Research Institute [Créteil, France] (VRI), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), This work was supported by NIH grants to B.H.H. (R37 AI50529, R01 AI 120810, R01 AI 114266), G.S. (R37 AI66998), and YYY (R01 AI 120860), and the BEAT-HIV Delaney Consortium (UM1 AI 126620), DFG CRC 1279 and SPP 1923, an Advanced ERC investigator grant to F.K., and a grant from Sidaction to M.M.-T. N.H. was supported by VRI (Créteil, France) and T.G.-T. by the Pasteur-Paris University PhD program. We thank the IDMIT center for access to the stellar Imaging platform and acknowledge the Imagopole France–BioImaging infrastructure, supported by the French ANR (10-INSB-04-01, Investments for the Future), for advice and access to the CV1000 system. S.J. and E.L. were part of IGradU Ulm and S.J. was supported by the DFG RTG CEMMA., We thank K. Regensburger, M. Mayer, R. Linsenmeyer, S. Engelhart, D. Krnavek, S. Heine, and J. Hampe for technical assistance, S. Sopper, K. Töpfer, and T. Schultheiss for support with flow cytometry and Nirav Patel and Greg Tharp of the Yerkes NHP Genomics Core for microarray analysis., University of Pennsylvania [Philadelphia], Innsbruck Medical University [Austria] (IMU), HIV, Inflammation et persistance, Institut Pasteur [Paris], and Vaccine Research Institute (VRI)
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., In contrast to HIV, simian immunodeficiency viruses (SIV) do not cause disease in their hosts, and the reasons for this are unclear. Here, Joas et al. incorporate two putative HIV virulence factors into SIV and study effects in infected monkeys, suggesting that species-specific host factors are responsible for HIV pathogenesis.