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

Nature communications, 2018-04, Vol.9 (1), p.1371-16, Article 1371 [Peer Reviewed Journal]

2018. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License. ;Attribution ;The Author(s) 2018 ;ISSN: 2041-1723 ;EISSN: 2041-1723 ;DOI: 10.1038/s41467-018-03762-3 ;PMID: 29636452

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Title:
Species-specific host factors rather than virus-intrinsic virulence determine primate lentiviral pathogenicity
Author: Joas, Simone ; Parrish, Erica H ; Gnanadurai, Clement W ; Lump, Edina ; Stürzel, Christina M ; Parrish, Nicholas F ; Learn, Gerald H ; Sauermann, Ulrike ; Neumann, Berit ; Rensing, Kerstin Mätz ; Fuchs, Dietmar ; Billingsley, James M ; Bosinger, Steven E ; Silvestri, Guido ; Apetrei, Cristian ; Huot, Nicolas ; Garcia-Tellez, Thalia ; Müller-Trutwin, Michaela ; Hotter, Dominik ; Sauter, Daniel ; Stahl-Hennig, Christiane ; Hahn, Beatrice H ; Kirchhoff, Frank
Subjects: Acquired immune deficiency syndrome ; AIDS ; Amino Acid Sequence ; Animal biology ; Animals ; Bone Marrow Stromal Antigen 2 ; Bone Marrow Stromal Antigen 2 - genetics ; Bone Marrow Stromal Antigen 2 - immunology ; CD3 antigen ; CD3 Complex ; CD3 Complex - genetics ; CD3 Complex - immunology ; Cell activation ; Cercopithecus aethiops ; Female ; Gene expression ; Gene Expression Regulation ; HIV ; HIV-1 ; HIV-1 - growth & development ; HIV-1 - pathogenicity ; Host Specificity ; Human health and pathology ; Human immunodeficiency virus ; Human Immunodeficiency Virus Proteins ; Human Immunodeficiency Virus Proteins - genetics ; Human Immunodeficiency Virus Proteins - immunology ; Humans ; Immunodeficiency ; Immunology ; Infectious diseases ; Inflammation ; Lentiviruses, Primate ; Lentiviruses, Primate - growth & development ; Lentiviruses, Primate - pathogenicity ; Life Sciences ; Lymphocyte Activation ; Lymphocytes ; Lymphocytes T ; Microbiology and Parasitology ; Monkeys ; Monkeys & apes ; nef Gene Products, Human Immunodeficiency Virus ; nef Gene Products, Human Immunodeficiency Virus - genetics ; nef Gene Products, Human Immunodeficiency Virus - immunology ; Nef protein ; NF-kappa B ; NF-kappa B - genetics ; NF-kappa B - immunology ; NF-κB protein ; Pandemics ; Pathogenicity ; Pathogens ; Proteins ; Sequence Alignment ; Signal Transduction ; Simian Immunodeficiency Virus ; Simian Immunodeficiency Virus - growth & development ; Simian Immunodeficiency Virus - pathogenicity ; T cell receptors ; Transcription activation ; Transcription, Genetic ; Vaccines ; Viral Load ; Viral Regulatory and Accessory Proteins ; Viral Regulatory and Accessory Proteins - genetics ; Viral Regulatory and Accessory Proteins - immunology ; Viremia ; Virology ; Virulence ; Virulence factors ; Virus Replication ; Viruses ; Vpu protein
Is Part Of: Nature communications, 2018-04, Vol.9 (1), p.1371-16, Article 1371
Description: 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.
Publisher: England: Nature Publishing Group
Language: English
Identifier: ISSN: 2041-1723
EISSN: 2041-1723
DOI: 10.1038/s41467-018-03762-3
PMID: 29636452
Source: AUTh Library subscriptions: ProQuest Central
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Species-specific host factors rather than virus-intrinsic virulence determine primate lentiviral pathogenicity

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