The neonatal Fc receptor is a pan-echovirus receptor.

Authors:
Stefanie Morosky
Stefanie Morosky
University of Pittsburgh
United States
Alexandra I Wells
Alexandra I Wells
National Institute of Allergy and Infectious Diseases
Sandra Schamus
Sandra Schamus
University of Pittsburgh Cancer Institute
United States
Christopher J Bakkenist
Christopher J Bakkenist
University of Pittsburgh School of Medicine
United States
Carolyn B Coyne
Carolyn B Coyne
University of Pittsburgh
Pittsburgh | United States

Proc Natl Acad Sci U S A 2019 02 11;116(9):3758-3763. Epub 2019 Feb 11.

Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, PA 15224;

Echoviruses are amongst the most common causative agents of aseptic meningitis worldwide and are particularly devastating in the neonatal population, where they are associated with severe hepatitis, neurological disease, including meningitis and encephalitis, and even death. Here, we identify the neonatal Fc receptor (FcRn) as a pan-echovirus receptor. We show that loss of expression of FcRn or its binding partner beta 2 microglobulin (β2M) renders cells resistant to infection by a panel of echoviruses at the stage of virus attachment, and that a blocking antibody to β2M inhibits echovirus infection in cell lines and in primary human intestinal epithelial cells. We also show that expression of human, but not mouse, FcRn renders nonpermissive human and mouse cells sensitive to echovirus infection and that the extracellular domain of human FcRn directly binds echovirus particles and neutralizes infection. Lastly, we show that neonatal mice expressing human FcRn are more susceptible to echovirus infection by the enteral route. Our findings thus identify FcRn as a pan-echovirus receptor, which may explain the enhanced susceptibility of neonates to echovirus infections.

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Source
http://dx.doi.org/10.1073/pnas.1817341116DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6397586PMC
February 2019
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