title: The Neonatal Fc receptor (FcRn) enhances human immunodeficiency virus type 1 (HIV-1) transcytosis across epithelial cells.
abstract: The mechanisms by which human immunodeficiency virus type 1 (HIV-1) crosses mucosal surfaces to establish infection are unknown. Acidic genital secretions of HIV-1-infected women contain HIV-1 likely coated by antibody. We found that the combination of acidic pH and Env-specific IgG, including that from cervicovaginal and seminal fluids of HIV-1-infected individuals, augmented transcytosis across epithelial cells as much as 20-fold compared with Env-specific IgG at neutral pH or non-specific IgG at either pH. Enhanced transcytosis was observed with clinical HIV-1 isolates, including transmitted/founder strains, and was eliminated in Fc neonatal receptor (FcRn)-knockdown epithelial cells. Non-neutralizing antibodies allowed similar or less transcytosis than neutralizing antibodies. However, the ratio of total:infectious virus was higher for neutralizing antibodies, indicating that they allowed transcytosis while blocking infectivity of transcytosed virus. Immunocytochemistry revealed abundant FcRn expression in columnar epithelia lining the human endocervix and penile urethra. Acidity and Env-specific IgG enhance transcytosis of virus across epithelial cells via FcRn and could facilitate translocation of virus to susceptible target cells following sexual exposure.
authors.affiliation: Division of Infectious Diseases, Department of Medicine, University of California, Irvine School of Medicine, Irvine, California, United States of America.
authors.forename: Sandeep
authors.initials: S
authors.lastname: Gupta
authors.forename: Johannes S
authors.initials: JS
authors.lastname: Gach
authors.forename: Juan C
authors.initials: JC
authors.lastname: Becerra
authors.forename: Tran B
authors.initials: TB
authors.lastname: Phan
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Pudney
authors.forename: Zina
authors.initials: Z
authors.lastname: Moldoveanu
authors.forename: Sarah B
authors.initials: SB
authors.lastname: Joseph
authors.forename: Gary
authors.initials: G
authors.lastname: Landucci
authors.forename: Medalyn Jude
authors.initials: MJ
authors.lastname: Supnet
authors.forename: Li-Hua
authors.initials: LH
authors.lastname: Ping
authors.forename: Davide
authors.initials: D
authors.lastname: Corti
authors.forename: Brian
authors.initials: B
authors.lastname: Moldt
authors.forename: Zdenek
authors.initials: Z
authors.lastname: Hel
authors.forename: Antonio
authors.initials: A
authors.lastname: Lanzavecchia
authors.forename: Ruth M
authors.initials: RM
authors.lastname: Ruprecht
authors.forename: Dennis R
authors.initials: DR
authors.lastname: Burton
authors.forename: Jiri
authors.initials: J
authors.lastname: Mestecky
authors.forename: Deborah J
authors.initials: DJ
authors.lastname: Anderson
authors.forename: Donald N
authors.initials: DN
authors.lastname: Forthal
mesh_terms: D045744:Cell Line, Tumor; D002584:Cervix Uteri / Q000276:immunology / Q000473:pathology / Q000821:virology; D004847:Epithelial Cells / Q000276:immunology* / Q000473:pathology; D005260:Female; D015483:HIV Antibodies / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology* / Q000472:pathogenicity; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007074:Immunoglobulin G / Q000276:immunology*; D008297:Male; D011961:Receptors, Fc / Q000276:immunology*; D012661:Semen / Q000276:immunology; D057900:Transcytosis / Q000276:immunology*; D014521:Urethra / Q000276:immunology / Q000473:pathology / Q000821:virology
chemical_list: D015483:HIV Antibodies; D015395:Histocompatibility Antigens Class I; D007074:Immunoglobulin G; D011961:Receptors, Fc; C100688:Fc receptor, neonatal