title: Rapid Inflammasome Activation following Mucosal SIV Infection of Rhesus Monkeys.
abstract: The earliest events following mucosal HIV-1 infection, prior to measurable viremia, remain poorly understood. Here, by detailed necropsy studies, we show that the virus can rapidly disseminate following mucosal SIV infection of rhesus monkeys and trigger components of the inflammasome, both at the site of inoculation and at early sites of distal virus spread. By 24 hr following inoculation, a proinflammatory signature that lacked antiviral restriction factors was observed in viral RNA-positive tissues. The early innate response included expression of NLRX1, which inhibits antiviral responses, and activation of the TGF-β pathway, which negatively regulates adaptive immune responses. These data suggest a model in which the virus triggers specific host mechanisms that suppress the generation of antiviral innate and adaptive immune responses in the first few days of infection, thus facilitating its own replication. These findings have important implications for the development of vaccines and other strategies to prevent infection.
authors.affiliation: Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA; Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA. Electronic address: dbarouch@bidmc.harvard.edu.
authors.forename: Dan H
authors.initials: DH
authors.lastname: Barouch
authors.affiliation: Case Western Reserve University, Cleveland, OH 44106, USA.
authors.forename: Khader
authors.initials: K
authors.lastname: Ghneim
authors.affiliation: AIDS and Cancer Virus Program, Leidos Biomedical Research, Frederick National Laboratory, Frederick, MD 21702, USA.
authors.forename: William J
authors.initials: WJ
authors.lastname: Bosche
authors.affiliation: AIDS and Cancer Virus Program, Leidos Biomedical Research, Frederick National Laboratory, Frederick, MD 21702, USA.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Li
authors.affiliation: AIDS and Cancer Virus Program, Leidos Biomedical Research, Frederick National Laboratory, Frederick, MD 21702, USA.
authors.forename: Brian
authors.initials: B
authors.lastname: Berkemeier
authors.affiliation: AIDS and Cancer Virus Program, Leidos Biomedical Research, Frederick National Laboratory, Frederick, MD 21702, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Hull
authors.affiliation: Case Western Reserve University, Cleveland, OH 44106, USA.
authors.forename: Sanghamitra
authors.initials: S
authors.lastname: Bhattacharyya
authors.affiliation: Case Western Reserve University, Cleveland, OH 44106, USA.
authors.forename: Mark
authors.initials: M
authors.lastname: Cameron
authors.affiliation: Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
authors.forename: Jinyan
authors.initials: J
authors.lastname: Liu
authors.affiliation: Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
authors.forename: Kaitlin
authors.initials: K
authors.lastname: Smith
authors.affiliation: Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
authors.forename: Erica
authors.initials: E
authors.lastname: Borducchi
authors.affiliation: Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
authors.forename: Crystal
authors.initials: C
authors.lastname: Cabral
authors.affiliation: Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
authors.forename: Lauren
authors.initials: L
authors.lastname: Peter
authors.affiliation: Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
authors.forename: Amanda
authors.initials: A
authors.lastname: Brinkman
authors.affiliation: Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
authors.forename: Mayuri
authors.initials: M
authors.lastname: Shetty
authors.affiliation: Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
authors.forename: Hualin
authors.initials: H
authors.lastname: Li
authors.affiliation: Bioqual, Rockville, MD 20852, USA.
authors.forename: Courtney
authors.initials: C
authors.lastname: Gittens
authors.affiliation: Bioqual, Rockville, MD 20852, USA.
authors.forename: Chantelle
authors.initials: C
authors.lastname: Baker
authors.affiliation: Bioqual, Rockville, MD 20852, USA.
authors.forename: Wendeline
authors.initials: W
authors.lastname: Wagner
authors.affiliation: Bioqual, Rockville, MD 20852, USA.
authors.forename: Mark G
authors.initials: MG
authors.lastname: Lewis
authors.affiliation: New England Primate Research Center, Southborough, MA 01772, USA.
authors.forename: Arnaud
authors.initials: A
authors.lastname: Colantonio
authors.affiliation: University of Massachusetts Medical School, Worcester, MA 01605, USA.
authors.forename: Hyung-Joo
authors.initials: HJ
authors.lastname: Kang
authors.affiliation: University of Massachusetts Medical School, Worcester, MA 01605, USA.
authors.forename: Wenjun
authors.initials: W
authors.lastname: Li
authors.affiliation: AIDS and Cancer Virus Program, Leidos Biomedical Research, Frederick National Laboratory, Frederick, MD 21702, USA.
authors.forename: Jeffrey D
authors.initials: JD
authors.lastname: Lifson
authors.affiliation: AIDS and Cancer Virus Program, Leidos Biomedical Research, Frederick National Laboratory, Frederick, MD 21702, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Piatak
authors.affiliation: Case Western Reserve University, Cleveland, OH 44106, USA.
authors.forename: Rafick-Pierre
authors.initials: RP
authors.lastname: Sekaly
mesh_terms: D000818:Animals; D001853:Bone Marrow / Q000276:immunology; D007113:Immunity, Innate; D018928:Immunity, Mucosal; D058847:Inflammasomes / Q000276:immunology*; D007694:Killer Cells, Natural / Q000276:immunology; D008253:Macaca mulatta; D024101:Mitochondrial Proteins / Q000378:metabolism; D009000:Monocytes / Q000276:immunology; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology* / Q000821:virology*; D015302:Simian Immunodeficiency Virus / Q000502:physiology*; D013601:T-Lymphocytes / Q000276:immunology; D059467:Transcriptome; D016212:Transforming Growth Factor beta / Q000378:metabolism; D014779:Virus Replication
chemical_list: D058847:Inflammasomes; D024101:Mitochondrial Proteins; D016212:Transforming Growth Factor beta