title: Th17 Cells Are Preferentially Infected Very Early after Vaginal Transmission of SIV in Macaques.
abstract: The difficulty in detecting rare infected cells immediately after mucosal HIV transmission has hindered our understanding of the initial cells targeted by the virus. Working with the macaque simian immunodeficiency virus (SIV) vaginal challenge model, we developed methodology to identify discrete foci of SIV (mac239) infection 48 hr after vaginal inoculation. We find infectious foci throughout the reproductive tract, from labia to ovary. Phenotyping infected cells reveals that SIV has a significant bias for infection of CCR6+ CD4+ T cells. SIV-infected cells expressed the transcriptional regulator RORγt, confirming that the initial target cells are specifically of the Th17 lineage. Furthermore, we detect host responses to infection, as evidenced by apoptosis, cell lysis, and phagocytosis of infected cells. Thus, our analysis identifies Th17-lineage CCR6+ CD4+ T cells as primary targets of SIV during vaginal transmission. This opens new opportunities for interventions to protect these cells and prevent HIV transmission.
authors.affiliation: Department of Cellular and Molecular Biology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Stieh
authors.affiliation: Department of Cellular and Molecular Biology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA.
authors.forename: Edgar
authors.initials: E
authors.lastname: Matias
authors.affiliation: Tulane National Primate Research Center, Tulane University School of Medicine, Covington, LA 70433, USA.
authors.forename: Huanbin
authors.initials: H
authors.lastname: Xu
authors.affiliation: Department of Preventive Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA.
authors.forename: Angela J
authors.initials: AJ
authors.lastname: Fought
authors.affiliation: Tulane National Primate Research Center, Tulane University School of Medicine, Covington, LA 70433, USA.
authors.forename: James L
authors.initials: JL
authors.lastname: Blanchard
authors.affiliation: Tulane National Primate Research Center, Tulane University School of Medicine, Covington, LA 70433, USA.
authors.forename: Preston A
authors.initials: PA
authors.lastname: Marx
authors.affiliation: Tulane National Primate Research Center, Tulane University School of Medicine, Covington, LA 70433, USA.
authors.forename: Ronald S
authors.initials: RS
authors.lastname: Veazey
authors.affiliation: Department of Cellular and Molecular Biology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA. Electronic address: thope@northwestern.edu.
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Hope
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D015658:HIV Infections / Q000276:immunology / Q000635:transmission / Q000821:virology*; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D008253:Macaca mulatta; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology / Q000635:transmission / Q000821:virology*; D015302:Simian Immunodeficiency Virus / Q000235:genetics / Q000502:physiology*; D058504:Th17 Cells / Q000276:immunology / Q000821:virology*; D014621:Vagina / Q000276:immunology / Q000821:virology*