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

Adam J. Ericsen, Michael Lauck, Mariel S. Mohns, Sarah R. DiNapoli, James P. Mutschler, Justin M. Greene, Jason T. Weinfurter, Gabrielle Lehrer-Brey, Trent M. Prall, Samantha M. Gieger, Connor R. Buechler, Kristin A. Crosno, Eric J. Peterson, Matthew R. Reynolds, Roger W. Wiseman, Benjamin Burwitz, Jacob Estes, Jonah Sacha, Thomas C. Friedrich, Jason M. BrenchleyDavid H. O’Connor

Research output: Contribution to journalArticle

15 Scopus citations

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.

Original languageEnglish (US)
Article numbere1006048
JournalPLoS Pathogens
Volume12
Issue number12
DOIs
StatePublished - Dec 7 2016

    Fingerprint

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Immunology
  • Molecular Biology
  • Genetics
  • Virology

Cite this

Ericsen, A. J., Lauck, M., Mohns, M. S., DiNapoli, S. R., Mutschler, J. P., Greene, J. M., Weinfurter, J. T., Lehrer-Brey, G., Prall, T. M., Gieger, S. M., Buechler, C. R., Crosno, K. A., Peterson, E. J., Reynolds, M. R., Wiseman, R. W., Burwitz, B., Estes, J., Sacha, J., Friedrich, T. C., ... O’Connor, D. H. (2016). Microbial Translocation and Inflammation Occur in Hyperacute Immunodeficiency Virus Infection and Compromise Host Control of Virus Replication. PLoS Pathogens, 12(12), [e1006048]. https://doi.org/10.1371/journal.ppat.1006048