Binding of neoFc receptor traps intermediate of pocket
factor expulsion from echovirus 18
David Buchta 1, Yevgen Levdansky 2,
Tibor Füzik 1, Liya Mukhamedova 1, Jana Moravcová 1
, Dominik Hrebik 1 , Jan Terje Andersen 3, 4, Pavel
Plevka 1
1Structural Virology,
Central European Institute of Technology, Masaryk University, Kamenice 753/5,
62500 Brno, Czech Republic
2Max Planck Institute
for Developmental Biology, Max-Planck-Ring 5, 72076, Tübingen, Germany
3Centre for Immune Regulation
(CIR) and Department of Biosciences, University of Oslo, N-0316 Oslo, Norway
4 - CIR and Department of Immunology, Oslo University
Hospital Rikshospitalet and University of Oslo, Norway, PO Box 4950, N-0424
Oslo, Norway
pavel.plevka@ceitec.muni.cz
Echovirus 18 (E-18) is a worldwide
distributed human pathogen that causes aseptic meningitis, leukoencephalitis,
and acute exanthema. To infect cells E-18 utilizes neonatal-Fc receptor (neoFc),
which is expressed in placenta and brain-blood barrier cells of both children
and adults. In spite of the importance of the virus, its structure remained
unknown and no treatment is available.
Here, we present the structures of virion,
complex of virion with neoFc, activated particle, and empty capsid of E18
determined to the resolutions of 2.9 – 3.4 Å using cryo-electron
microscopy. E-18, as many other enteroviruses, has hydrophobic pocket in capsid
protein VP1, which is filled by a compound known as pocket factor.
Binding of neoFc to E-18 induced half-way
release of a pocket factor. The neoFc-triggered conformational changes of the
capsid provide experimental evidence for former hypotheses that
receptor-binding can induce ejection of pocket factors from particles of
enteroviruses.
1. Brunel, D., et al. (2007). "Fatal Echovirus 18
Leukoencephalitis in a Child." Journal of Clinical Microbiology 45(6):
2068-2071.
2. Kusuhara, K., et al. (2008). "An echovirus type 18
outbreak in a neonatal intensive care unit." European Journal of Pediatrics
167(5): 587-589.