The neonatal Fc receptor (FcRn) enhances human immunodeficiency virus type 1 (HIV-1) transcytosis across epithelial cells

Gupta, Sandeep; Gach, Johannes S.; Becerra, Juan C.; Phan, Tran B.; Pudney, Jeffrey; Moldoveanu, Zina; Joseph, Sarah B.; Landucci, Gary; Supnet, Medalyn Jude; Ping, Li-Hua; Corti, Davide; Moldt, Brian; Hel, Zdenek; Lanzavecchia, Antonio; Ruprecht, Ruth M.; Burton, Dennis R.; Mestecky, Jiri; Anderson, Deborah J.; Forthal, Donald N.

doi:10.1371/journal.ppat.1003776

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Journal article

The neonatal Fc receptor (FcRn) enhances human immunodeficiency virus type 1 (HIV-1) transcytosis across epithelial cells

Gupta, Sandeep Division of Infectious Diseases, Department of Medicine, University of California, Irvine School of Medicine, Irvine, California, United States of America
Gach, Johannes S. Division of Infectious Diseases, Department of Medicine, University of California, Irvine School of Medicine, Irvine, California, United States of America
Becerra, Juan C. Division of Infectious Diseases, Department of Medicine, University of California, Irvine School of Medicine, Irvine, California, United States of America
Phan, Tran B. Division of Infectious Diseases, Department of Medicine, University of California, Irvine School of Medicine, Irvine, California, United States of America
Pudney, Jeffrey Department of Obstetrics and Gynecology, Boston University School of Medicine, Boston, Massachusetts, United States of America
Moldoveanu, Zina Department of Microbiology, University of Alabama at Birmingham, Birmingham, Alabama, United States of America
Joseph, Sarah B. Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America - Center for AIDS Research, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America
Landucci, Gary Division of Infectious Diseases, Department of Medicine, University of California, Irvine School of Medicine, Irvine, California, United States of America
Supnet, Medalyn Jude Division of Infectious Diseases, Department of Medicine, University of California, Irvine School of Medicine, Irvine, California, United States of America
Ping, Li-Hua Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America - Center for AIDS Research, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America
Corti, Davide Institute for Research in Biomedicine (IRB), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland - Humabs BioMed SA, Bellinzona, Switzerland
Moldt, Brian Department of Immunology and Microbial Science, International AIDS Vaccine Initiative Neutralizing Antibody Center and Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute, La Jolla, California, United States of America
Hel, Zdenek Department of Pathology, University of Alabama at Birmingham, Birmingham, Alabama, United States of America
Lanzavecchia, Antonio Institute for Research in Biomedicine (IRB), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland - Institute of Microbiology, Eidgenössische Technische Hochschule (ETH) Zürich, Zürich, Switzerland
Ruprecht, Ruth M. Texas Biomedical Research Institute, San Antonio, Texas, United States of America
Burton, Dennis R. Department of Immunology and Microbial Science, International AIDS Vaccine Initiative Neutralizing Antibody Center and Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute, La Jolla, California, United States of America - Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology, and Harvard University, Boston, Massachusetts, United States of America
Mestecky, Jiri Department of Microbiology, University of Alabama at Birmingham, Birmingham, Alabama, United States of America - Institute of Immunology and Microbiology, First School of Medicine, Charles University, Prague, Czech Republic
Anderson, Deborah J. Department of Obstetrics and Gynecology, Boston University School of Medicine, Boston, Massachusetts, United States of America
Forthal, Donald N. Division of Infectious Diseases, Department of Medicine, University of California, Irvine School of Medicine, Irvine, California, United States of America

21.11.2013

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Plos pathogens. - 2013, vol. 9, no. 11, p. e1003776

English 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.

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