The major echovirus group is genetically coherent and related to coxsackie B viruses

Huttunen, Pasi; Santti, Juhana; Pulli, Timo; Hyypiä, Timo

doi:10.1099/0022-1317-77-4-715

Cited by 64 publications

(49 citation statements)

References 36 publications

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“…Coxsackievirus B3 interaction with p56 lck and cleavage of dystrophin by the viral 2A proteinase are believed to contribute to disease progression in the heart (29)(30)(31). Coxsackie B viruses and EV1 are highly related, suggesting common mechanisms of pathogenesis (32,33). The development of a transgenic mouse model to study EV1 infection should provide valuable insight into how echoviruses and other enteroviruses cause CNS and heart disease.…”

Section: Discussionmentioning

confidence: 99%

Transgenic mouse model for echovirus myocarditis and paralysis

Hughes

Thaker

Racaniello

2003

Proc. Natl. Acad. Sci. U.S.A.

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Echoviruses have been implicated in multiple human disease syndromes, including aseptic meningitis, paralysis, and heart disease, but no animal model is available for studying the pathogenesis of infection. Production of human integrin very late antigen 2, a receptor for echovirus type 1, in transgenic mice conferred susceptibility to viral infection. Intracerebral inoculation of newborn transgenic mice with echovirus leads to paralysis and wasting. No disease was observed in infected nontransgenic mice. In paralyzed mice significant damage was observed in the outer layers of the cerebrum, and numerous condensed neuronal nuclei were present. In contrast, intracerebral inoculation of adolescent (3-to 4-weekold) transgenic mice with echovirus type 1 did not lead to paralysis but an acute wasting phenotype and myocarditis. These findings establish human very late antigen 2 transgenic mice as a model for echovirus pathogenesis. E choviruses, like polioviruses and coxsackieviruses, are nonenveloped RNA viruses that are members of the Enterovirus group of the family Picornaviridae. It is estimated that 10-15 million illnesses are caused each year by nonpolio enteroviruses in the United States (1). Although the vast majority of these illnesses are not serious, a wide range of potentially fatal human diseases, including aseptic meningitis, encephalitis, paralysis, type I diabetes mellitus, and myocarditis, have been associated with echovirus infections (2).Members of the enteric cytopathogenic human orphan group of viruses (echoviruses) were initially distinguished from coxsackieviruses by their inability to replicate and cause disease in newborn mice (3). Because a small animal model is not available, much of what is known about echovirus pathogenesis is inferred from epidemiological surveillance studies and mouse models for coxsackievirus and poliovirus pathogenesis. As is the case for poliovirus, the cellular receptor is most likely a major determinant of the restricted host range of echoviruses (4-7). A receptor molecule that is both sufficient and necessary to mediate virus binding and entry has been identified for only 1 of the 31 echovirus serotypes, echovirus type 1 (EV1) (8). A cellular receptor for EV1 is human very late antigen 2 (VLA-2), a heterodimer comprising one ␣2 subunit and one ␤1 subunit (integrin ␣2͞␤1). EV1 interacts with the collagen binding I domain of human ␣2 integrin subunits (9). Although EV1 binding and entry are mediated solely by the ␣2 subunit, association of an ␣2 subunit with a ␤1 subunit is required for proper transport of ␣2͞␤1 integrin to the cell surface (10). Production of the ␣2 polypeptide in rodent cells is sufficient to render these cells susceptible to infection by EV1, indicating that human-␣2͞mouse-␤1 heterodimers can serve as functional EV1 receptors (8, 11). Widespread cell and tissue synthesis of integrin ␣2͞␤1 is consistent with the hypothesis that many target organs are involved in EV1 pathogenesis (12).Transgenic mice that produce human cell receptors for infectious ag...

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Section: Discussionmentioning

confidence: 99%

Transgenic mouse model for echovirus myocarditis and paralysis

Hughes

Thaker

Racaniello

2003

Proc. Natl. Acad. Sci. U.S.A.

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“…Cleavage site P5h P4h P3h P2h P1h P1 P2 P3 P4 P5 CBV) and enteroviruses 67-71 (Pulli et al, 1995 ;Huttunen et al, 1996 ;Hyypia$ et al, 1997). It is clear that all except HPeV1 and HPeV2 are typical enteroviruses and thus these viruses are the only currently known members of the parechoviruses which infect humans.…”

Section: Residuementioning

confidence: 99%

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

Ghazi

Hughes

Hyypiä

et al. 1998

Journal of General Virology

108

101

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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

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“…All CV-B viruses, CV-A9, EV-69, EV-73 and all echoviruses form HEV-B; CV-A1, CV-A11, CV-A13, CV-A15, CV-A17 to CV-A22 and CV-A24 form HEV-C; and EV-68 and EV-70 form HEV-D. This classification is based on previous subdivisions of enteroviruses into four genetic groups after analysis of the VP2, 3D and VP1 regions, as well as complete genomes (Dahllund et al, 1995;Pulli et al, 1995;Huttunen et al, 1996;Pöyry et al, 1996;Oberste et al, 1999a, b).…”

Section: Introductionmentioning

confidence: 99%

Sequencing of ‘untypable’ enteroviruses reveals two new types, EV-77 and EV-78, within human enterovirus type B and substitutions in the BC loop of the VP1 protein for known types

Nordér

Bjerregaard

Magnius

et al. 2003

Journal of General Virology

132

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The N-terminal part of VP1 was sequenced for 43 enterovirus isolates that could not initially be neutralized with LBM pools or in-house antisera. Most isolates were found to belong to human enterovirus type A (HEV-A) and HEV-B (18 isolates of each). All HEV-A isolates could be typed by sequencing, with CV (coxsackievirus)-A16 and EV (enterovirus)-71 being dominant (nine and seven isolates, respectively). These types thus seem to have diverged more from their prototypes than the other types. Among the HEV-B isolates, E-18 dominated with five isolates that became typable after filtration. The virus type obtained by molecular typing was verified for 28 of the other patient isolates by neutralization using high-titre monovalent antisera or LBM pools. Twenty-two of the other 30 'untypable' isolates had substitutions in the VP1 protein within or close to the BC loop. Two closely related HEV-B isolates diverged by 19?4 % from E-15, the most similar prototype. Two non-neutralizable HEV-C isolates split off from the CV-A13/CV-A18 branch, from which they diverged by 15?7-18?2 %. Three of the six non-neutralizable isolates, W553-130/99, W543-122/99 and W137-126/99, diverged by >24?2 % from the most similar prototype in the compared region. The complete VP1 was therefore sequenced and found to diverge by >29 % from all prototypes and by >28 % from each other. Strains similar to W553-130/99 that have been identified in the USA are tentatively designated EV-74. The two other isolates fulfil the molecular criterion for being new types. Since strains designated EV-75 and EV-76 have been identified in the USA, we have proposed the tentative designations EV-77 and EV-78 for these two new members of HEV-B.

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The major echovirus group is genetically coherent and related to coxsackie B viruses

Cited by 64 publications

References 36 publications

Transgenic mouse model for echovirus myocarditis and paralysis

Transgenic mouse model for echovirus myocarditis and paralysis

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

Sequencing of ‘untypable’ enteroviruses reveals two new types, EV-77 and EV-78, within human enterovirus type B and substitutions in the BC loop of the VP1 protein for known types

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