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

Abstract

SUMMARY 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 protection against SIV infection by vaccination prevents enteropathogen emergence.

Intestinal virome changes precede autoimmunity in type I diabetes-susceptible children

“…Changes in various components of the microbiome have been observed in association with multiple human diseases (1)(2)(3)(4). Prominent among diseases that are influenced by microorganisms is type 1 diabetes (T1D), a disease involving an autoimmune attack on the insulin-secreting beta cells of the pancreatic islets of Langerhans.…”

“…Changes in intestinal viruses have been observed in patients with inflammatory bowel disease and AIDS (2)(3)(4)12), indicating that changes in the virome can be associated with infectious and inflammatory diseases. In some cases, these changes involve eukaryotic viruses, whereas in other cases, disease-associated changes in bacteriophages have been identified.…”

The gut microbiome and HIV-1 pathogenesis

“…In 2012, Handley and colleagues used next-generation sequencing of fecal samples to be the first to demonstrate that pathogenic SIV infection is associated with the expansion of the enteric virome[92]. In a follow up longitudinal study of SIV-infected monkeys, progression of SIV infection to AIDS was associated with expansion of gastrointestinal adenoviruses, adeno-associated viruses and picornaviruses[91]. Moreover, effective vaccination and specific vaccine-elicited immune responses were associated with a prevention of expansion of the fecal virome[91].…”

“…In a follow up longitudinal study of SIV-infected monkeys, progression of SIV infection to AIDS was associated with expansion of gastrointestinal adenoviruses, adeno-associated viruses and picornaviruses[91]. Moreover, effective vaccination and specific vaccine-elicited immune responses were associated with a prevention of expansion of the fecal virome[91]. Findings in HIV-1 infection paralleled those of SIV infection with expansion of enteric adenoviruses associated with AIDS whereas, in the absence of immunodeficiency, the enteric virome remained largely unchanged[43].…”

Lactobacillus-Deficient Cervicovaginal Bacterial Communities Are Associated with Increased HIV Acquisition in Young South African Women

“…The recent development of high throughput sequencing technologies to characterize the human microbiome has significantly improved our understanding of the role of the microbiome in diseases such as obesity, inflammatory bowel disease, colorectal cancer (Marchesi et al, 2016) and HIV-induced AIDS (Handley et al, 2016; Monaco et al, 2016). While these studies have focused on the enteric microbiome, less is understood regarding the role of the cervicovaginal microbiome in disease susceptibility, particularly in the developing world.…”