title: Altered Virome and Bacterial Microbiome in Human Immunodeficiency Virus-Associated Acquired Immunodeficiency Syndrome.
abstract: Human immunodeficiency virus (HIV) infection is associated with increased intestinal translocation of microbial products and enteropathy as well as alterations in gut bacterial communities. However, whether the enteric virome contributes to this infection and resulting immunodeficiency remains unknown. We characterized the enteric virome and bacterial microbiome in a cohort of Ugandan patients, including HIV-uninfected or HIV-infected subjects and those either treated with anti-retroviral therapy (ART) or untreated. Low peripheral CD4 T cell counts were associated with an expansion of enteric adenovirus sequences and this increase was independent of ART treatment. Additionally, the enteric bacterial microbiome of patients with lower CD4 T counts exhibited reduced phylogenetic diversity and richness with specific bacteria showing differential abundance, including increases in Enterobacteriaceae, which have been associated with inflammation. Thus, immunodeficiency in progressive HIV infection is associated with alterations in the enteric virome and bacterial microbiome, which may contribute to AIDS-associated enteropathy and disease progression.
authors.affiliation: Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: Cynthia L
authors.initials: CL
authors.lastname: Monaco
authors.affiliation: Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA.
authors.forename: David B
authors.initials: DB
authors.lastname: Gootenberg
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, 63110, USA.
authors.forename: Guoyan
authors.initials: G
authors.lastname: Zhao
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, 63110, USA.
authors.forename: Scott A
authors.initials: SA
authors.lastname: Handley
authors.affiliation: Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA.
authors.forename: Musie S
authors.initials: MS
authors.lastname: Ghebremichael
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, 63110, USA; Department of Molecular Microbiology, Washington University School of Medicine, Saint Louis, MO 63110, USA.
authors.forename: Efrem S
authors.initials: ES
authors.lastname: Lim
authors.affiliation: Division of Infectious Diseases, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
authors.forename: Alex
authors.initials: A
authors.lastname: Lankowski
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, 63110, USA.
authors.forename: Megan T
authors.initials: MT
authors.lastname: Baldridge
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, 63110, USA.
authors.forename: Craig B
authors.initials: CB
authors.lastname: Wilen
authors.affiliation: Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA.
authors.forename: Meaghan
authors.initials: M
authors.lastname: Flagg
authors.affiliation: Vedanta Biosciences, Cambridge, MA 02139, USA.
authors.forename: Jason M
authors.initials: JM
authors.lastname: Norman
authors.affiliation: Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: Brian C
authors.initials: BC
authors.lastname: Keller
authors.affiliation: Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA.
authors.forename: Jesús Mario
authors.initials: JM
authors.lastname: Luévano
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, 63110, USA; Department of Molecular Microbiology, Washington University School of Medicine, Saint Louis, MO 63110, USA.
authors.forename: David
authors.initials: D
authors.lastname: Wang
authors.affiliation: Médecins Sans Frontières Epicentre, 1956 Mbarara, Uganda.
authors.forename: Yap
authors.initials: Y
authors.lastname: Boum
authors.affiliation: Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, CA 94143, USA.
authors.forename: Jeffrey N
authors.initials: JN
authors.lastname: Martin
authors.affiliation: Department of Medicine, University of California San Francisco, San Francisco, CA 94110, USA.
authors.forename: Peter W
authors.initials: PW
authors.lastname: Hunt
authors.affiliation: Division of Infectious Diseases, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA; Harvard School of Public Health, Boston, MA 02114, USA.
authors.forename: David R
authors.initials: DR
authors.lastname: Bangsberg
authors.affiliation: Division of Infectious Diseases, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Siedner
authors.affiliation: Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA; Division of Infectious Diseases, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA. Electronic address: dkwon@mgh.harvard.edu.
authors.forename: Douglas S
authors.initials: DS
authors.lastname: Kwon
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, 63110, USA. Electronic address: virgin@wustl.edu.
authors.forename: Herbert W
authors.initials: HW
authors.lastname: Virgin
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000150:complications / Q000276:immunology / Q000382:microbiology* / Q000821:virology*; D044966:Anti-Retroviral Agents / Q000627:therapeutic use; D001419:Bacteria / Q000145:classification / Q000235:genetics / Q000302:isolation & purification*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D000069196:Gastrointestinal Microbiome; D014644:Genetic Variation; D019053:HIV Enteropathy / Q000209:etiology; D064368:Healthy Volunteers; D006801:Humans; D064307:Microbiota; D010802:Phylogeny; D014454:Uganda; D014780:Viruses / Q000145:classification / Q000235:genetics / Q000302:isolation & purification*
chemical_list: D044966:Anti-Retroviral Agents
keywords: AIDS; AIDS enteropathy; HIV; adenovirus; microbiome; systemic inflammation; virome