Dataset Information

Microbial Translocation and Inflammation Occur in Hyperacute Immunodeficiency Virus Infection and Compromise Host Control of Virus Replication.

ABSTRACT: Within the first three weeks of human immunodeficiency virus (HIV) infection, virus replication peaks in peripheral blood. Despite the critical, causal role of virus replication in determining transmissibility and kinetics of progression to acquired immune deficiency syndrome (AIDS), there is limited understanding of the conditions required to transform the small localized transmitted founder virus population into a large and heterogeneous systemic infection. Here we show that during the hyperacute "pre-peak" phase of simian immunodeficiency virus (SIV) infection in macaques, high levels of microbial DNA transiently translocate into peripheral blood. This, heretofore unappreciated, hyperacute-phase microbial translocation was accompanied by sustained reduction of lipopolysaccharide (LPS)-specific antibody titer, intestinal permeability, increased abundance of CD4+CCR5+ T cell targets of virus replication, and T cell activation. To test whether increasing gastrointestinal permeability to cause microbial translocation would amplify viremia, we treated two SIV-infected macaque 'elite controllers' with a short-course of dextran sulfate sodium (DSS)-stimulating a transient increase in microbial translocation and a prolonged recrudescent viremia. Altogether, our data implicates translocating microbes as amplifiers of immunodeficiency virus replication that effectively undermine the host's capacity to contain infection.

SUBMITTER: Ericsen AJ

PROVIDER: S-EPMC5142784 | biostudies-literature | 2016 Dec

REPOSITORIES: biostudies-literature

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Microbial Translocation and Inflammation Occur in Hyperacute Immunodeficiency Virus Infection and Compromise Host Control of Virus Replication.

Ericsen Adam J AJ Lauck Michael M Mohns Mariel S MS DiNapoli Sarah R SR Mutschler James P JP Greene Justin M JM Weinfurter Jason T JT Lehrer-Brey Gabrielle G Prall Trent M TM Gieger Samantha M SM Buechler Connor R CR Crosno Kristin A KA Peterson Eric J EJ Reynolds Matthew R MR Wiseman Roger W RW Burwitz Benjamin J BJ Estes Jacob D JD Sacha Jonah B JB Friedrich Thomas C TC Brenchley Jason M JM O'Connor David H DH

PLoS pathogens 20161207 12

Within the first three weeks of human immunodeficiency virus (HIV) infection, virus replication peaks in peripheral blood. Despite the critical, causal role of virus replication in determining transmissibility and kinetics of progression to acquired immune deficiency syndrome (AIDS), there is limited understanding of the conditions required to transform the small localized transmitted founder virus population into a large and heterogeneous systemic infection. Here we show that during the hyperac ...[more]

PMID: 27926931

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Project description:BackgroundDespite effective antiretroviral therapy (ART), patients with chronic human immunodeficiency virus (HIV) infection have increased microbial translocation and systemic inflammation. Alterations in the intestinal microbiota may play a role in microbial translocation and inflammation.MethodsWe profiled the fecal microbiota by pyrosequencing the gene encoding 16S ribosomal RNA (rRNA) and measured markers of microbial translocation and systemic inflammation in 21 patients who had chronic HIV infection and were receiving suppressive ART (cases) and 16 HIV-uninfected controls.ResultsThe fecal microbial community composition was significantly different between cases and controls. The relative abundance of Proteobacteria, Gammaproteobacteria, Enterobacteriales, Enterobacteriaceae, Erysipelotrichi, Erysipelotrichales, Erysipelotrichaceae, and Barnesiella was significantly enriched in cases, whereas that of Rikenellaceae and Alistipes was depleted. The plasma soluble CD14 level (sCD14) was significantly higher and the endotoxin core immunoglobulin M (IgM) level lower in cases, compared with controls. There were significant positive correlations between the relative abundances of Enterobacteriales and Enterobacteriaceae and the sCD14 level; the relative abundances of Gammaproteobacteria, Enterobacteriales, and Enterobacteriaceae and the interleukin 1β (IL-1β) level; the relative abundances of Enterobacteriales and Enterobacteriaceae and the interferon γ level; and the relative abundances of Erysipelotrichi and Barnesiella and the TNF-α level. There were negative correlations between endotoxin core IgM and IL-1β levels.ConclusionsPatients who have chronic HIV infection and are receiving suppressive ART display intestinal dysbiosis associated with increased microbial translocation and significant associations between specific taxa and markers of microbial translocation and systemic inflammation. This was an exploratory study, the findings of which need to be confirmed.

Dataset Information

Microbial Translocation and Inflammation Occur in Hyperacute Immunodeficiency Virus Infection and Compromise Host Control of Virus Replication.

Publications

Microbial Translocation and Inflammation Occur in Hyperacute Immunodeficiency Virus Infection and Compromise Host Control of Virus Replication.

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