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PMID: 20554778 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Interaction of alphaVbeta3 and alphaVbeta6 integrins with human parechovirus 1.

Journal of virology ·Vol. 84 ·No. 17 ·2010-09-00 ·Pages 8509-19

Seitsonen J, Susi P, Heikkilä O, Sinkovits RS, Laurinmäki P, Hyypiä T, Butcher SJ

Abstract

Human parechovirus (HPEV) infections are very common in early childhood and can be severe in neonates. It has been shown that integrins are important for cellular infectivity of HPEV1 through experiments using peptide blocking assays and function-blocking antibodies to alpha(V) integrins. The interaction of HPEV1 with alpha(V) integrins is presumably mediated by a C-terminal RGD motif in the capsid protein VP1. We characterized the binding of integrins alpha(V)beta(3) and alpha(V)beta(6) to HPEV1 by biochemical and structural studies. We showed that although HPEV1 bound efficiently to immobilized integrins, alpha(V)beta(6) bound more efficiently than alpha(V)beta(3) to immobilized HPEV1. Moreover, soluble alpha(V)beta(6), but not alpha(V)beta(3), blocked HPEV1 cellular infectivity, indicating that it is a high-affinity receptor for HPEV1. We also showed that HPEV1 binding to integrins in vitro could be partially blocked by RGD peptides. Using electron cryo-microscopy and image reconstruction, we showed that HPEV1 has the typical T=1 (pseudo T=3) organization of a picornavirus. Complexes of HPEV1 and integrins indicated that both integrin footprints reside between the 5-fold and 3-fold symmetry axes. This result does not match the RGD position predicted from the coxsackievirus A9 X-ray structure but is consistent with the predicted location of this motif in the shorter C terminus found in HPEV1. This first structural characterization of a parechovirus indicates that the differences in receptor binding are due to the amino acid differences in the integrins rather than to significantly different viral footprints.

MeSH Terms
Amino Acid Sequence Antigens, Neoplasm/chemistry,genetics,metabolism Cell Line Humans Integrin alphaVbeta3/chemistry,genetics,metabolism Integrins/chemistry,genetics,metabolism Molecular Conformation Molecular Sequence Data Parechovirus/chemistry,genetics,metabolism Picornaviridae Infections/metabolism,virology Protein Binding Sequence Alignment Viral Proteins/chemistry,genetics,metabolism
Chemicals
Antigens, Neoplasm Integrin alphaVbeta3 Integrins Viral Proteins integrin alphavbeta6
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Seitsonen Jani
Department of Biosciences, Institute of Biotechnology, PO Box 65, Viikinkaari 1, FIN-00014 University of Helsinki, Finland.
Susi Petri
Heikkilä Outi
Sinkovits Robert S
Laurinmäki Pasi
Hyypiä Timo
Butcher Sarah J
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Article Info
Journal
Journal of virology
Abbr.
J Virol
ISSN
1098-5514
DOI
10.1128/JVI.02176-09
Published
2010-09-00
Epub
2010-00-16
Pages
8509-19
Language
English
Region
United States
NLM ID
0113724
PMCID
PMC2919010
Subset
IM
Grants
NIAID NIH HHS · R01 AI-079095 · United States
NIGMS NIH HHS · R37 GM033050 · United States
NIGMS NIH HHS · R37 GM-033050 · United States
NIAID NIH HHS · R56 AI079095 · United States
NIAID NIH HHS · P01 AI045976 · United States
External Links
PubMed source DOI: 10.1128/JVI.02176-09 PMC Full Text View journal details
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