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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-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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