The Neonatal Fc Receptor (FcRn) Enhances Human Immunodeficiency Virus Type 1 (HIV-1) Transcytosis across Epithelial Cells

PLoS Pathogens

Brian Moldt¹  Gary Landucci¹  Ruth M. Ruprecht²  Zina Moldoveanu³  Jeffrey Pudney⁴  Dennis R. Burton⁵  Tran B. Phan⁶  Li-Hua Ping⁶  Medalyn Jude Supnet⁶  Sandeep Gupta⁶  Juan C. Becerra⁶  Johannes S. Gach⁶  Antonio Lanzavecchia⁷  Jiri Mestecky⁸  Zdenek Hel⁸  Deborah J. Anderson⁹  Davide Corti^1,10  Sarah B. Joseph^1,10  Donald N. Forthal^1,11 

[1] Center for AIDS Research, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America;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;Department of Microbiology, University of Alabama at Birmingham, Birmingham, Alabama, United States of America;Department of Obstetrics and Gynecology, Boston University School of Medicine, Boston, Massachusetts, United States of America;Department of Pathology, University of Alabama at Birmingham, Birmingham, Alabama, United States of America;Division of Infectious Diseases, Department of Medicine, University of California, Irvine School of Medicine, Irvine, California, United States of America;Humabs BioMed SA, Bellinzona, Switzerland;Institute for Research in Biomedicine, Bellinzona, Switzerland;Institute of Microbiology, Eidgenössische Technische Hochschule (ETH) Zürich, Zürich, Switzerland;Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America;Texas Biomedical Research Institute, San Antonio, Texas, United States of America

关键词: Antibodies;    HIV-1;    Secretion;    Semen;    Epithelial cells;    Immunohistochemistry techniques;    Enzyme-linked immunoassays;    Immune complex;   

DOI  :  10.1371/journal.ppat.1003776

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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.

【 授权许可】

CC BY