title: SIV Infection-Mediated Changes in Gastrointestinal Bacterial Microbiome and Virome Are Associated with Immunodeficiency and Prevented by Vaccination.
abstract: AIDS caused by simian immunodeficiency virus (SIV) infection is associated with gastrointestinal disease, systemic immune activation, and, in cross-sectional studies, changes in the enteric virome. Here we performed a longitudinal study of a vaccine cohort to define the natural history of changes in the fecal metagenome in SIV-infected monkeys. Matched rhesus macaques were either uninfected or intrarectally challenged with SIV, with a subset receiving the Ad26 vaccine, an adenovirus vector expressing the viral Env/Gag/Pol antigens. Progression of SIV infection to AIDS was associated with increased detection of potentially pathogenic viruses and bacterial enteropathogens. Specifically, adenoviruses were associated with an increased incidence of gastrointestinal disease and AIDS-related mortality. Viral and bacterial enteropathogens were largely absent from animals protected by the vaccine. These data suggest that the SIV-associated gastrointestinal disease is associated with the presence of both viral and bacterial enteropathogens and that protection against SIV infection by vaccination prevents enteropathogen emergence.
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, Saint Louis, MO 63110, USA. Electronic address: shandley@pathology.wustl.edu.
authors.forename: Scott A
authors.initials: SA
authors.lastname: Handley
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, Saint Louis, MO 63110, USA.
authors.forename: Chandni
authors.initials: C
authors.lastname: Desai
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, Saint 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, Saint Louis, MO 63110, USA.
authors.forename: Lindsay
authors.initials: L
authors.lastname: Droit
authors.affiliation: Department of Medicine, Washington University School of Medicine, Saint Louis, MO 63110, USA.
authors.forename: Cynthia L
authors.initials: CL
authors.lastname: Monaco
authors.affiliation: Department of Molecular Microbiology, Washington University School of Medicine, Saint Louis, MO 63110, USA.
authors.forename: Andrew C
authors.initials: AC
authors.lastname: Schroeder
authors.affiliation: Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA; Ragon Institute of MGH, MIT, and Harvard, Boston, MA 02114, USA.
authors.forename: Joseph P
authors.initials: JP
authors.lastname: Nkolola
authors.affiliation: Washington University Pain Center and Department of Anesthesiology, Washington University School of Medicine, Saint Louis, MO 63110, USA.
authors.forename: Megan E
authors.initials: ME
authors.lastname: Norman
authors.affiliation: Section of Anatomic Pathology, Department of Biomedical Sciences, Cornell University College of Veterinary Medicine, Ithaca, NY 14853, USA.
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Miller
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, Saint 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: Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA; Ragon Institute of MGH, MIT, and Harvard, Boston, MA 02114, USA.
authors.forename: Dan H
authors.initials: DH
authors.lastname: Barouch
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, Saint Louis, MO 63110, USA. Electronic address: virgin@wustl.edu.
authors.forename: Herbert W
authors.initials: HW
authors.lastname: Virgin
mesh_terms: D000818:Animals; D001419:Bacteria / Q000145:classification* / Q000235:genetics / Q000302:isolation & purification*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D005767:Gastrointestinal Diseases / Q000209:etiology / Q000382:microbiology / Q000517:prevention & control / Q000821:virology; D000069196:Gastrointestinal Microbiome; D014644:Genetic Variation; D008137:Longitudinal Studies; D008253:Macaca mulatta; D018449:SAIDS Vaccines / Q000008:administration & dosage / Q000276:immunology; D016097:Simian Acquired Immunodeficiency Syndrome / Q000150:complications / Q000276:immunology / Q000473:pathology*; D015302:Simian Immunodeficiency Virus / Q000276:immunology / Q000472:pathogenicity*; D014780:Viruses / Q000145:classification* / Q000235:genetics / Q000302:isolation & purification*
chemical_list: D018449:SAIDS Vaccines
keywords: AIDS; SIV; adenovirus; circovirus; microbiome; picornavirus; vaccine; virome