Entry of Coxsackievirus A9 into Host Cells: Specific Interactions with αvβ3 Integrin, the Vitronectin Receptor

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101

Picornaviruses have been divided into five genera until recently, when a sixth genus, Parechovirus, was defined. Human parechovirus type 1 (HPeV1 ; formerly echovirus 22) was the first recognized member of this genus and preliminary sequence analysis of echovirus 23 [now renamed human parechovirus type 2 (HPeV2)] suggested that it is also a parechovirus. Here we describe the complete nucleotide and predicted amino acid sequences of HPeV2, which indicate a close relationship to HPeV1 throughout the genome. Sequence covariance in the 5h untranslated region allows a prediction of the secondary structure, which indicates that these parechoviruses have a type 2 internal ribosome

Section: Cgeh F Ghazi and Others F Ghazi And Othersmentioning

confidence: 99%

Molecular analysis of human parechovirus type 2 (formerly echovirus 23).

Ghazi

Hughes

Hyypiä

et al. 1998

108

101

“…In support of this is the fact that, in comparison to FMDV, the N terminus of VP1 in ERAV is highly hydrophilic (Varrasso et al, 2001). In FMDV, the N terminus of VP1 is confined to the interior of the capsid, within a deep and predominantly hydrophobic cleft formed by the interface between VP2 and VP3 (Acharya et al, 1989;Curry et al, 1997;Lea et al, 1994), although N-terminal residues of PV-1, which are known also to be located internally in the capsid, have been shown to elicit virus-neutralizing antibodies (Fricks & Hogle, 1990;Roivainen et al, 1994).…”

mentioning

confidence: 99%

Mapping epitopes in equine rhinitis A virus VP1 recognized by antibodies elicited in response to infection of the natural host

Stevenson

Hartley

Huang

et al. 2003

Equine rhinitis A virus (ERAV) is an important respiratory pathogen of horses and is of additional interest because of its close relationship and common classification with foot-and-mouth disease virus (FMDV). As is the case with FMDV, the VP1 capsid protein of ERAV has been shown to be a target of neutralizing antibodies. In FMDV VP1, such antibodies commonly recognize linear epitopes present in the bG-bH loop region. To map linear B cell epitopes in ERAV VP1, overlapping fragments spanning its length were expressed in Escherichia coli as glutathione S-transferase (GST) fusion proteins. These fusion proteins were tested for reactivity with sera from ERAV-infected horses and with polyclonal sera from ERAV-immunized rabbits and mice. Regions at the N-and C-termini as well as the bE-bF and the bG-bH loop regions contained B cell epitopes that elicited antibodies in the natural host. GST fusion proteins of these regions also elicited antibodies following immunization of rabbits and mice, which, in general, strongly recognized native ERAV VP1 but which were non-neutralizing. It is concluded that the N-terminal region of ERAV VP1, in particular, contains strong B cell epitopes.Equine rhinitis A virus (ERAV) is an important respiratory pathogen of horses. Disease is characterized by fever (41±0?5˚C) and clinical signs that include nasal discharge, coughing, anorexia, pharyngitis and lymphadenitis (Plummer, 1962). ERAV is classified with foot-and-mouth disease virus (FMDV), albeit as a separate cluster, in the genus Aphthovirus, family Picornaviridae. ERAV shares many physico-chemical and biological properties with FMDV and the genome structures and sequences of the two viruses are also similar (Li et al., 1996;Newman et al., 1973;Plummer, 1963;Studdert & Gleeson, 1978;Wutz et al., 1996).Picornavirus capsid proteins VP1, VP2 and VP3 share structural homology and are composed of wedge-shaped, eight-stranded, b-barrels, which differ in the size and conformation of the connecting loops between their strands and the extensions of their N-and C-termini (Rueckert, 2001). The amino acid sequences of the loops that connect the b-strands and the N-and C-terminal regions that extend from the b-barrel domain give each picornavirus its distinct morphology and antigenicity (Mateu, 1995;Rueckert, 2001). For example, the surface loops of VP1, VP2 and VP3 of poliovirus type 1 (PV-1) and human rhinovirus type 14 capsid structures protrude from the virion surface to form the receptor-binding canyon, as well as the major antigenic sites of these viruses. In comparison, the VP1 protein within the relatively smooth surface of FMDV particles contains a linear peptide, the bG-bH loop, which is both the dominant neutralization epitope and is also involved in receptor binding to various integrins via an RGD motif (Berinstein et al., 1995;Danen et al., 1995;Jackson et al., 2000;Mateu et al., 1995;Stanway, 1990;Strohmaier et al., 1982).In marked contrast to FMDV and human rhinoviruses, the predicted amino acid sequence of ERAV P1 and, in particu...

“…Stanway et al, 1994), and a different pair (avb3 and avb6) for CAV-9 (Heikkilä et al, 2009;Roivainen et al, 1991Roivainen et al, , 1994Williams et al, 2004). Likewise, in GMK cells, the reactive heterodimers are probably either avb3 or avb6, since, according to our earlier studies, the expression level of heterodimer avb1 was extremely low in GMK cells .…”

Section: Discussionmentioning

confidence: 99%

Vitronectin receptors, v integrins, are recognized by several non-RGD-containing echoviruses in a continuous laboratory cell line and also in primary human Langerhans' islets and endothelial cells

Ylipaasto

Eskelinen

Salmela

et al. 2009

Previously published data suggest that the RGD-recognizing integrin, avb3, known as the vitronectin receptor, acts as a cellular receptor for RGD-containing enteroviruses, coxsackievirus A9 (CAV-9) and echovirus 9 (E-9), in several continuous cell lines as well as in primary human Langerhans' islets. As this receptor is also capable of binding the ligands by a non-RGDdependent mechanism, we investigated whether vitronectin receptors, av integrins, might act as receptors for other echoviruses that do not have the RGD motif. Blocking experiments with polyclonal anti-avb3 antibody showed that both primary human islets and a continuous laboratory cell line of green monkey kidney origin (GMK) are protected similarly from the adverse effects of several non-RGD-containing echovirus (E-7, -11, -25, -30, -32) infections. In contrast, corresponding studies on primary human endothelial cells showed that the receptor works only for E-25, E-30, E-32 and CAV-9. The inhibitory effect of the antibody was not restricted to prototype strains of echoviruses, as GMK cells infected with several field isolates of the corresponding serotypes were also protected from virus-induced cytopathic effects. Co-localization of virus particles with the receptor molecules in both GMK and primary human endothelial cells was demonstrated by live-cell stainings and confocal microscopy. Remarkably, in spite of similar virus-receptor co-localization and a comparable protective effect of the avb3 antibody, the entry pathways of the studied virus strains seemed to be divergent.