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

Date Published: December 7, 2016

Publisher: Public Library of Science

Author(s): 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 J. Burwitz, Jacob D. Estes, Jonah B. Sacha, Thomas C. Friedrich, Jason M. Brenchley, David H. O’Connor, Daniel C. Douek.


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.

Partial Text

In HIV infection, there is mounting evidence that host-virus interactions occurring prior to peak viremia serve as key determinants of durable host containment of virus replication[1]. Despite the importance of these hyperacute phase phenomena in dictating the pace of virus dissemination and disease progression, there is limited understanding of actionable targets for manipulating the host environment in which these early interactions take place.

The systemic dissemination and replication of certain enteric viruses has been tied to their interaction with gastrointestinal bacteria[31]. In the gastrointestinal tract, mouse mammary tumor virus, an orally transmitted retrovirus, becomes coated in bacterial LPS, which causes circulating virions to provoke interleukin-10 production, which aids in virus subversion of cellular immunity[32]. Intriguingly, elicitation of anti-gp41 antibodies in a recent HIV vaccination study was purportedly compromised by epitope sharing between commensally encoded antigen and the viral gp41 glycoprotein[33]. These data, when considered alongside evidence that gastrointestinal barrier integrity is compromised early during HIV infection[34], point toward microbial products being beneficial to incipient HIV infection.




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