title: 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.
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Wisconsin-Madison, Madison, Wisconsin, United States Of America.|Virology Training Program, University of Wisconsin-Madison, Madison, Wisconsin, United States Of America.
authors.forename: Adam J
authors.identifier: http://orcid.org/0000-0003-4176-8270
authors.initials: AJ
authors.lastname: Ericsen
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Wisconsin-Madison, Madison, Wisconsin, United States Of America.
authors.forename: Michael
authors.identifier: http://orcid.org/0000-0003-2813-3705
authors.initials: M
authors.lastname: Lauck
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Wisconsin-Madison, Madison, Wisconsin, United States Of America.
authors.forename: Mariel S
authors.identifier: http://orcid.org/0000-0002-3609-8447
authors.initials: MS
authors.lastname: Mohns
authors.affiliation: Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Disease, National Institutes of Health, Bethesda, Maryland, United States Of America.
authors.forename: Sarah R
authors.initials: SR
authors.lastname: DiNapoli
authors.affiliation: Wisconsin National Primate Research Center, Madison, Wisconsin, United States Of America.
authors.forename: James P
authors.identifier: http://orcid.org/0000-0002-6912-0233
authors.initials: JP
authors.lastname: Mutschler
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Wisconsin-Madison, Madison, Wisconsin, United States Of America.
authors.forename: Justin M
authors.initials: JM
authors.lastname: Greene
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Wisconsin-Madison, Madison, Wisconsin, United States Of America.
authors.forename: Jason T
authors.identifier: http://orcid.org/0000-0001-8076-2598
authors.initials: JT
authors.lastname: Weinfurter
authors.affiliation: Wisconsin National Primate Research Center, Madison, Wisconsin, United States Of America.
authors.forename: Gabrielle
authors.initials: G
authors.lastname: Lehrer-Brey
authors.affiliation: Wisconsin National Primate Research Center, Madison, Wisconsin, United States Of America.
authors.forename: Trent M
authors.identifier: http://orcid.org/0000-0003-0635-4152
authors.initials: TM
authors.lastname: Prall
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Wisconsin-Madison, Madison, Wisconsin, United States Of America.
authors.forename: Samantha M
authors.initials: SM
authors.lastname: Gieger
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Wisconsin-Madison, Madison, Wisconsin, United States Of America.
authors.forename: Connor R
authors.initials: CR
authors.lastname: Buechler
authors.affiliation: Wisconsin National Primate Research Center, Madison, Wisconsin, United States Of America.
authors.forename: Kristin A
authors.initials: KA
authors.lastname: Crosno
authors.affiliation: Wisconsin National Primate Research Center, Madison, Wisconsin, United States Of America.
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Peterson
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Wisconsin-Madison, Madison, Wisconsin, United States Of America.
authors.forename: Matthew R
authors.identifier: http://orcid.org/0000-0002-1484-6408
authors.initials: MR
authors.lastname: Reynolds
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Wisconsin-Madison, Madison, Wisconsin, United States Of America.
authors.forename: Roger W
authors.initials: RW
authors.lastname: Wiseman
authors.affiliation: Vaccine & Gene Therapy Institute, Oregon National Primate Research Center, and Department of Molecular Microbiology & Immunology, Oregon Health & Science University, Portland, Oregon, United States Of America.
authors.forename: Benjamin J
authors.identifier: http://orcid.org/0000-0001-7767-022X
authors.initials: BJ
authors.lastname: Burwitz
authors.affiliation: AIDS and Cancer Virus Program, Frederick National Laboratory for Cancer Research, Leidos Biomedical Research, Inc., Frederick, Maryland, United States Of America.
authors.forename: Jacob D
authors.initials: JD
authors.lastname: Estes
authors.affiliation: Vaccine & Gene Therapy Institute, Oregon National Primate Research Center, and Department of Molecular Microbiology & Immunology, Oregon Health & Science University, Portland, Oregon, United States Of America.
authors.forename: Jonah B
authors.initials: JB
authors.lastname: Sacha
authors.affiliation: Wisconsin National Primate Research Center, Madison, Wisconsin, United States Of America.|Department of Pathobiological Sciences, University of Wisconsin-Madison, Madison, Wisconsin, United States Of America.
authors.forename: Thomas C
authors.identifier: http://orcid.org/0000-0001-9831-6895
authors.initials: TC
authors.lastname: Friedrich
authors.affiliation: Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Disease, National Institutes of Health, Bethesda, Maryland, United States Of America.
authors.forename: Jason M
authors.initials: JM
authors.lastname: Brenchley
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Wisconsin-Madison, Madison, Wisconsin, United States Of America.|Wisconsin National Primate Research Center, Madison, Wisconsin, United States Of America.
authors.forename: David H
authors.initials: DH
authors.lastname: O'Connor
mesh_terms: D000818:Animals; D004279:DNA, Viral / Q000097:blood*; D018450:Disease Progression; D005260:Female; D005434:Flow Cytometry; D016130:Immunophenotyping; D007249:Inflammation / Q000276:immunology / Q000821:virology; D008213:Lymphocyte Activation / Q000276:immunology; D008252:Macaca fascicularis; D008297:Male; D016133:Polymerase Chain Reaction; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology / Q000821:virology*; D015302:Simian Immunodeficiency Virus / Q000276:immunology / Q000472:pathogenicity*; D014766:Viremia / Q000821:virology*; D014779:Virus Replication / Q000276:immunology
chemical_list: D004279:DNA, Viral