Intracellular neutralization of viral infection in polarized epithelial cells by neonatal Fc receptor (FcRn)-mediated IgG transport

• DOI: 10.1073/pnas.1115348108
• Publication Date: 2011-11-01T04:21:08Z
• Authors: Yu Bai; Lilin Ye; Devin B. Tesar; Haichen Song; Deming Zhao; Pamela J. Björkman; Derry C. Roopenian; Xiaoping Zhu
• Keywords: Neonatal Fc receptor

IgG was traditionally thought to neutralize virions by blocking their attachment or penetration into mucosal epithelial cells, a common site of exposure viruses. However, we describe an intracellular neutralizing action for influenza hemagglutinin-specific monoclonal antibody, Y8-10C2 (Y8), which has activity only at acidic pH. When Y8 applied the basolateral surface Madin–Darby canine kidney cells expressing rat neonatal Fc receptor (FcRn), it significantly reduced viral replication following apical cell monolayer virus. Virus neutralization mAb dependent on FcRn expression and its transport IgG. As both bind partners pH, is proposed carry out antiviral intracellularly. Furthermore, virus, mAb, colocalized within endosomes, possibly inhibiting fusion envelopes with endosomal membranes during primary uncoating, preventing accumulation neutralized nucleoprotein antigen in nucleus. Prophylactic administration before challenge WT mice, but not FcRn-KO conferred protection from lethality, prevented weight loss, resulted significant reduction pulmonary virus titers, largely virus-induced lung pathology. Thus, this study reveals mechanism polarized that FcRn-mediated