title: Early type I Interferon response induces upregulation of human β-defensin 1 during acute HIV-1 infection.
abstract: HIV-1 is able to evade innate antiviral responses during acute infection to establish a chronic systemic infection which, in the absence of antiretroviral therapy (ART), typically progresses to severe immunodeficiency. Understanding these early innate immune responses against HIV-1 and their mechanisms of failure is relevant to the development of interventions to better prevent HIV-1 transmission. Human beta defensins (HBDs) are antibacterial peptides but have recently also been associated with control of viral replication. HBD1 and 2 are expressed in PBMCs as well as intestinal tissue, but their expression in vivo during HIV-1 infection has not been characterized. We demonstrate that during acute HIV-1 infection, HBD1 but not HBD2 is highly upregulated in circulating monocytes but returns to baseline levels during chronic infection. HBD1 expression in monocytes can be induced by HIV-1 in vitro, although direct infection may not entirely account for the increase in HBD1 during acute infection. We provide evidence that HIV-1 triggers antiviral IFN-α responses, which act as a potent inducer of HBD1. Our results show the first characterization of induction of an HBD during acute and chronic viral infection in humans. HBD1 has been reported to have low activity against HIV-1 compared to other defensins, suggesting that in vivo induced defensins may not significantly contribute to the robust early antiviral response against HIV-1. These data provide important insight into the in vivo kinetics of HBD expression, the mechanism of HBD1 induction by HIV-1, and the role of HBDs in the early innate response to HIV-1 during acute infection.
authors.affiliation: Ragon Institute of MGH, MIT, and Harvard, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, United States of America.
authors.forename: Björn
authors.identifier: http://orcid.org/0000-0001-9833-3169
authors.initials: B
authors.lastname: Corleis
authors.affiliation: Ragon Institute of MGH, MIT, and Harvard, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, United States of America.
authors.forename: Antonella C
authors.initials: AC
authors.lastname: Lisanti
authors.affiliation: Ragon Institute of MGH, MIT, and Harvard, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, United States of America.
authors.forename: Christian
authors.initials: C
authors.lastname: Körner
authors.affiliation: Ragon Institute of MGH, MIT, and Harvard, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, United States of America.
authors.forename: Abigail E
authors.initials: AE
authors.lastname: Schiff
authors.affiliation: Division of Infectious Diseases, Massachusetts General Hospital, Boston, Massachusetts, United States of America.
authors.forename: Eric S
authors.initials: ES
authors.lastname: Rosenberg
authors.affiliation: Ragon Institute of MGH, MIT, and Harvard, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, United States of America.
authors.forename: Todd M
authors.initials: TM
authors.lastname: Allen
authors.affiliation: Ragon Institute of MGH, MIT, and Harvard, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, United States of America.
authors.forename: Marcus
authors.initials: M
authors.lastname: Altfeld
authors.affiliation: Ragon Institute of MGH, MIT, and Harvard, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, United States of America.|Division of Infectious Diseases, Massachusetts General Hospital, Boston, Massachusetts, United States of America.
authors.forename: Douglas S
authors.initials: DS
authors.lastname: Kwon
mesh_terms: D015658:HIV Infections / Q000378:metabolism*; D015497:HIV-1; D006801:Humans; D007370:Interferon Type I / Q000096:biosynthesis*; D009000:Monocytes / Q000378:metabolism; D015854:Up-Regulation; D023083:beta-Defensins / Q000378:metabolism*
chemical_list: C406407:DEFB1 protein, human; D007370:Interferon Type I; D023083:beta-Defensins