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

• DOI: 10.1371/journal.ppat.1006048
• Publication Date: 2016-12-07T18:43:56Z
• Authors: Adam J. Ericsen; Michael Lauck; Mariel S. Mohns; Sarah R. DiNapoli; James P. Mutschler; Justin M. Greene; Jason T. Weinfurter; Gabrielle Lehrer-...; Trent M. Prall; Samantha M. Gieger; Connor R. Buechler; Kristin A. Crosno; Eric J. Peterson; Matthew R. Reynolds; Roger W. Wiseman; Benjamin J. Burwitz; Jacob D. Estes; Jonah B. Sacha; Thomas C. Friedrich; Jason M. Brenchley; David H. O’Connor
• Keywords: Viremia; Simian immunodeficiency virus

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