SIV Infection-Mediated Changes in Gastrointestinal Bacterial Microbiome and Virome Are Associated with Immunodeficiency and Prevented by Vaccination

• Published in: Cell host & microbe Vol. 19; no. 3; pp. 323 - 335
• Main Authors: Handley, Scott A., Desai, Chandni, Zhao, Guoyan, Droit, Lindsay, Monaco, Cynthia L., Schroeder, Andrew C., Nkolola, Joseph P., Norman, Megan E., Miller, Andrew D., Wang, David, Barouch, Dan H., Virgin, Herbert W.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 09.03.2016
• Subjects: adenovirus; AIDS; Animals; Bacteria - classification; Bacteria - genetics; Bacteria - isolation & purification; CD4-Positive T-Lymphocytes - immunology; circovirus; Gastrointestinal Diseases - etiology; Gastrointestinal Diseases - microbiology; Gastrointestinal Diseases - prevention & control; Gastrointestinal Diseases - virology; Gastrointestinal Microbiome; Genetic Variation; Longitudinal Studies; Macaca mulatta; microbiome; picornavirus; SAIDS Vaccines - administration & dosage; SAIDS Vaccines - immunology; Simian Acquired Immunodeficiency Syndrome - complications; Simian Acquired Immunodeficiency Syndrome - immunology; Simian Acquired Immunodeficiency Syndrome - pathology; Simian Immunodeficiency Virus - immunology; Simian Immunodeficiency Virus - pathogenicity; SIV; vaccine; virome; Viruses - classification; Viruses - genetics; Viruses - isolation & purification; virome; SIV; vaccine; circovirus; adenovirus; AIDS; microbiome; picornavirus
• ISSN: 1931-3128; 1934-6069; 1934-6069
• DOI: 10.1016/j.chom.2016.02.010

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. [Display omitted] •During SIV infection, enteric virome expansion dynamically changes as disease progresses•Specific enteropathogenic viruses are associated with enteric disease•Bacterial enteropathogens are associated with severe disease and immunocompromise•Prevention of SIV infection using vaccination prevents enteric virome expansion The causes of simian immunodeficiency virus (SIV) associated gastrointestinal disease are not well understood. Handley et al. describe the natural history of gastrointestinal virus and bacteria dynamics during SIV infection and identify associations between enteropathogens and disease. These negative effects were prevented by vaccination against SIV infection.