ジャーナル: J Virol / 年: 2010 タイトル: Interaction of alphaVbeta3 and alphaVbeta6 integrins with human parechovirus 1. 著者: Jani Seitsonen / Petri Susi / Outi Heikkilä / Robert S Sinkovits / Pasi Laurinmäki / Timo Hyypiä / Sarah J Butcher / 要旨: 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 ...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.
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添付データ
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試料の構成要素
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全体 : Purified human parechovirus 1 and integrin alphaV-beta6 in 1 mM M...
全体
名称: Purified human parechovirus 1 and integrin alphaV-beta6 in 1 mM MgCl2 in PBS buffer
要素
試料: Purified human parechovirus 1 and integrin alphaV-beta6 in 1 mM MgCl2 in PBS buffer
ウイルス: Human parecho virus 1
タンパク質・ペプチド: Integrin alphaV-beta6
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超分子 #1000: Purified human parechovirus 1 and integrin alphaV-beta6 in 1 mM M...
超分子
名称: Purified human parechovirus 1 and integrin alphaV-beta6 in 1 mM MgCl2 in PBS buffer タイプ: sample / ID: 1000 集合状態: Complete particle (60-mer) with the RNA genome inside with few integrin molecules attached Number unique components: 2
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超分子 #1: Human parecho virus 1
超分子
名称: Human parecho virus 1 / タイプ: virus / ID: 1 / Name.synonym: HPEV1 / 生物種: Human parecho virus 1 / ウイルスタイプ: VIRION / ウイルス・単離状態: STRAIN / ウイルス・エンベロープ: No / ウイルス・中空状態: No / Syn species name: HPEV1