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

Nat Commun. 2018 Apr 10;9(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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Bone Marrow Stromal Antigen 2 / genetics
  • Bone Marrow Stromal Antigen 2 / immunology
  • CD3 Complex / genetics
  • CD3 Complex / immunology
  • Chlorocebus aethiops
  • Female
  • Gene Expression Regulation
  • HIV-1 / growth & development
  • HIV-1 / pathogenicity*
  • Host Specificity*
  • Human Immunodeficiency Virus Proteins / genetics
  • Human Immunodeficiency Virus Proteins / immunology*
  • Humans
  • Lentiviruses, Primate / growth & development*
  • Lentiviruses, Primate / pathogenicity
  • Lymphocyte Activation
  • NF-kappa B / genetics
  • NF-kappa B / immunology
  • Sequence Alignment
  • Signal Transduction
  • Simian Immunodeficiency Virus / growth & development
  • Simian Immunodeficiency Virus / pathogenicity*
  • Transcription, Genetic
  • Viral Load
  • Viral Regulatory and Accessory Proteins / genetics
  • Viral Regulatory and Accessory Proteins / immunology*
  • Virulence
  • Virus Replication
  • nef Gene Products, Human Immunodeficiency Virus / genetics
  • nef Gene Products, Human Immunodeficiency Virus / immunology*

Substances

  • Bone Marrow Stromal Antigen 2
  • CD3 Complex
  • Human Immunodeficiency Virus Proteins
  • NF-kappa B
  • Viral Regulatory and Accessory Proteins
  • nef Gene Products, Human Immunodeficiency Virus
  • nef protein, Human immunodeficiency virus 1
  • vpu protein, Human immunodeficiency virus 1