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

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-?B 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.

SUBMITTER: Joas S

PROVIDER: S-EPMC5893559 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature

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

Joas Simone S Parrish Erica H EH Gnanadurai Clement W CW Lump Edina E Stürzel Christina M CM Parrish Nicholas F NF Learn Gerald H GH Sauermann Ulrike U Neumann Berit B Rensing Kerstin Mätz KM Fuchs Dietmar D Billingsley James M JM Bosinger Steven E SE Silvestri Guido G Apetrei Cristian C Huot Nicolas N Garcia-Tellez Thalia T Müller-Trutwin Michaela M Hotter Dominik D Sauter Daniel D Stahl-Hennig Christiane C Hahn Beatrice H BH Kirchhoff Frank F

Nature communications 20180410 1

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 ...[more]

PMID: 29636452

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

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

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