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
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Sequence
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Animals
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Bone Marrow Stromal Antigen 2 / genetics
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Bone Marrow Stromal Antigen 2 / immunology
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CD3 Complex / genetics
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CD3 Complex / immunology
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Chlorocebus aethiops
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Female
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Gene Expression Regulation
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HIV-1 / growth & development
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HIV-1 / pathogenicity*
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Host Specificity*
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Human Immunodeficiency Virus Proteins / genetics
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Human Immunodeficiency Virus Proteins / immunology*
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Humans
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Lentiviruses, Primate / growth & development*
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Lentiviruses, Primate / pathogenicity
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Lymphocyte Activation
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NF-kappa B / genetics
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NF-kappa B / immunology
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Sequence Alignment
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Signal Transduction
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Simian Immunodeficiency Virus / growth & development
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Simian Immunodeficiency Virus / pathogenicity*
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Transcription, Genetic
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Viral Load
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Viral Regulatory and Accessory Proteins / genetics
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Viral Regulatory and Accessory Proteins / immunology*
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Virulence
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Virus Replication
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nef Gene Products, Human Immunodeficiency Virus / genetics
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nef Gene Products, Human Immunodeficiency Virus / immunology*
Substances
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Bone Marrow Stromal Antigen 2
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CD3 Complex
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Human Immunodeficiency Virus Proteins
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NF-kappa B
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Viral Regulatory and Accessory Proteins
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nef Gene Products, Human Immunodeficiency Virus
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nef protein, Human immunodeficiency virus 1
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vpu protein, Human immunodeficiency virus 1