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

Species-specific host factors rather than virus-intrinsic virulence determine primate lentiviral pathogenicity.
Author Information (click to view)

Joas S, Parrish EH, Gnanadurai CW, Lump E, Stürzel CM, Parrish NF, Learn GH, Sauermann U, Neumann B, Rensing KM, Fuchs D, Billingsley JM, Bosinger SE, Silvestri G, Apetrei C, Huot N, Garcia-Tellez T, Müller-Trutwin M, Hotter D, Sauter D, Stahl-Hennig C, Hahn BH, Kirchhoff F,


Joas S, Parrish EH, Gnanadurai CW, Lump E, Stürzel CM, Parrish NF, Learn GH, Sauermann U, Neumann B, Rensing KM, Fuchs D, Billingsley JM, Bosinger SE, Silvestri G, Apetrei C, Huot N, Garcia-Tellez T, Müller-Trutwin M, Hotter D, Sauter D, Stahl-Hennig C, Hahn BH, Kirchhoff F, (click to view)

Joas S, Parrish EH, Gnanadurai CW, Lump E, Stürzel CM, Parrish NF, Learn GH, Sauermann U, Neumann B, Rensing KM, Fuchs D, Billingsley JM, Bosinger SE, Silvestri G, Apetrei C, Huot N, Garcia-Tellez T, Müller-Trutwin M, Hotter D, Sauter D, Stahl-Hennig C, Hahn BH, Kirchhoff F,

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Nature communications 2018 04 109(1) 1371 doi 10.1038/s41467-018-03762-3

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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