Analysis of sequence and pathogenic properties of two variants of encephalomyocarditis virus differing in a single amino acid in VP1

Nelsen-Salz, Birgit; Zimmermann, Albert; Wickert, Stephan; Arnold, Georg J.; Botta, Arne; Eggers, Hans J.; Kruppenbacher, J. P.

doi:10.1016/0168-1702(95)01257-5

Cited by 27 publications

(22 citation statements)

References 16 publications

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“…A further characterisation of this part of the neutralising site of CBV-4 revealed that by an exchange of amino acids Ser-86 to alanine, a complete loss of reactivity with CBV-4 specific antibodies were obtained, demonstrating the importance of this residue for neutralisation and serotyping [Halim and Ramsingh, 2000]. Mutations in the VP1 region have also been shown to change the pathogenicity of a picornavirus from a non-diabetogenic strain to a diabetogenic strain [Nelsen et al, 1996]. Enterovirus is associated with a variety of acute disease in humans (myocarditis, meningitis, Bornholm disease, herpangina, and respiratory illness).…”

Section: Introductionmentioning

confidence: 95%

Enterovirus infections with β‐cell tropic strains are frequent in siblings of children diagnosed with type 1 diabetes children and in association with elevated levels of GAD65 antibodies

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Tuvemo

2004

Journal of Medical Virology

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Enterovirus infections have been associated with type 1 diabetes in a number of reports. Recent prospective studies have suggested that enterovirus infections initiate the autoimmune process. Variation in virulence and replication pattern between strains of a serotype has also been shown. The aim was to study if there were specific Coxsackievirus strains that were associated more often with the type 1 diabetes children than with controls and/or siblings and to analyse if there was any time-relationship between such infections and the appearance of antibodies against glutamic acid decarboxylase 65 (GAD65). In the present study, serum was tested from newly diagnosed type 1 diabetes children, their siblings and matched controls for neutralising antibodies against different strains of Coxsackievirus B (CBV). Tests for the presence of antibodies against GAD65 in the same groups were also carried out. Newly diagnosed type 1 diabetes children revealed higher titres of neutralising antibodies against a strain of Coxsackievirus B4 (CBV-4, VD2921) that has been shown to cause persistent infection in human pancreatic islet cells. The type 1 diabetes child and its sibling often encountered the same infection. Among the former, 16 of 27 (59%) had a significant rise in neutralising antibodies. Eight of the type 1 diabetes children had such a rise against a recombinant strain, V89 4557. Among the siblings 10 of 13 (77%) had significant titre increases. Among the type 1 diabetes children, increasing neutralising titres was associated positively with increasing antibody levels against GAD65. All siblings with antibodies against GAD 65 had significant titre increase against any of the CBV strains.

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Section: Introductionmentioning

confidence: 95%

Enterovirus infections with β‐cell tropic strains are frequent in siblings of children diagnosed with type 1 diabetes children and in association with elevated levels of GAD65 antibodies

Frisk

Tuvemo

2004

Journal of Medical Virology

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“…Mengo virus, another cardiovirus that shares the same serotype as EMCV, was isolated from the cerebrospinal fluid of a paralyzed rhesus macaque in 1948 (8). EMCV 30/87 and 2887A/91 are more recent EMCV isolates obtained from aborted swine fetuses in the United States and Belgium, respectively, following natural EMCV outbreaks in domestic pigs (19,20).Nucleotide sequencing of most EMCV strains and Mengo virus has identified a poly(C) tract, consisting of 61 to 146 cytosine residues (C 61 to C 146 ), occasionally interrupted by 1 to 3 uridine residues, located at the 5Ј nontranslated region (NTR) of the positive-sense RNA genome (1,9,10,19,31,49). Studies to determine the role of the poly(C) tract in virus replication, virulence, and host range have produced conflicting findings.…”

mentioning

confidence: 99%

“…Nucleotide sequencing of most EMCV strains and Mengo virus has identified a poly(C) tract, consisting of 61 to 146 cytosine residues (C 61 to C 146 ), occasionally interrupted by 1 to 3 uridine residues, located at the 5Ј nontranslated region (NTR) of the positive-sense RNA genome (1,9,10,19,31,49). Studies to determine the role of the poly(C) tract in virus replication, virulence, and host range have produced conflicting findings.…”

mentioning

confidence: 99%

A Wild-Type Porcine Encephalomyocarditis Virus Containing a Short Poly(C) Tract Is Pathogenic to Mice, Pigs, and Cynomolgus Macaques

LaRue

Myers

Brewer

et al. 2003

J Virol

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Previous studies using wild-type Encephalomyocarditis virus (EMCV) and Mengo virus, which have long poly(C) tracts (61 to 146 C's) at the 5 nontranslated region of the genome, and variants of these viruses genetically engineered to truncate or substitute the poly(C) tracts have produced conflicting data on the role of the poly(C) tract in the virulence of these viruses. Analysis of the nucleotide sequence of an EMCV strain isolated from an aborted swine fetus (EMCV 30/87) revealed that the virus had a poly(C) tract that was 7-to 10-fold shorter than the poly(C) tracts of other EMCV strains and 4-fold shorter than that of Mengo virus. Subsequently, we investigated the virulence and pathogenesis of this naturally occurring short-poly(C)-tractcontaining virus in rodents, pigs, and nonhuman primates. Infection of C57BL/6 mice, pigs, and cynomolgus macaques resulted in similar EMCV 30/87 pathogenesis, with the heart and brain as the primary sites of infections in all three animals, but with different disease phenotypes. Sixteen percent of EMCV 30/87-infected pigs developed acute fatal cardiac failure, whereas the rest of the pigs were overtly asymptomatic for as long as 90 days postinfection (p.i.), despite extensive myocardial and central nervous system (CNS) pathological changes. In contrast, mice infected with >4 PFU of EMCV 30/87 developed acute encephalitis that resulted in the death of all animals (n ‫؍‬ 25) between days 2 and 7 p.i. EMCV 30/87-infected macaques remained overtly asymptomatic for 45 days, despite extensive myocardial and CNS pathological changes and viral persistence in more than 50% of the animals. The short poly(C) tract in EMCV 30/87 (CUC 5 UC 8 ) was comparable to that of strain 2887A/91 (C 10 UCUC 3 UC 10 ), another recent porcine isolate.Encephalomyocarditis virus (EMCV) is a picornavirus belonging to the Cardiovirus genus that infects many animal species including pigs (17), rodents (45), cattle (41), elephants (13), raccoons (47), marsupials (38), baboons, macaques, chimpanzees, and humans (2,16,21,38,44,45). Rats and mice are the natural hosts of the virus, but pigs are the most commonly and severely infected domestic animals (5, 36). EMCV strains have been isolated from primates, pigs, and rodents (8,15,20,22,24,29). EMCV Rueckert (EMCV R/45), the prototype strain, was isolated from a 5-year-old chimpanzee that suffered acute fatal myocarditis in 1945 (15), whereas EMC-M/58 virus was isolated from a naturally infected domestic pig suffering from severe myocarditis (29). A number of EMC-M/58 variants, including EMC-D/58, EMC-B/58, PV2/58, and PV21/58, were generated in laboratories and used to study the pathogenesis of viral diabetes (6,7,18,25,46,49). Mengo virus, another cardiovirus that shares the same serotype as EMCV, was isolated from the cerebrospinal fluid of a paralyzed rhesus macaque in 1948 (8). EMCV 30/87 and 2887A/91 are more recent EMCV isolates obtained from aborted swine fetuses in the United States and Belgium, respectively, following natural EMCV outbreaks in domestic ...

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“…For EMCV, the mutation N62D has been observed for the B279/95 strain after attenuation of the virus by serial passages on BHK-21 cells [8]. Furthermore, diabetogenic (PV2) and non-diabetogenic variants (PV7) of EMCV have been reported to differ by one mutation at residue 63 of the VP1 (Q63E/K) [25]. These results suggest that amino acid 64 may contribute to determining EMCV tropism and virulence.…”

Section: Discussionmentioning

confidence: 75%

Encephalomyocarditis virus may use different pathways to initiate infection of primary human cardiomyocytes

et al. 2011

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Encephalomyocarditis virus (EMCV) can infect a wide range of vertebrate species including swine and non-human primates, but few data are available for humans. We therefore wanted to gain further insight into the mechanisms involved in EMCV infection of human cells. For this purpose, we analyzed the permissiveness of primary human cardiomyocytes towards two strains of EMCV; a pig myocardial strain (B279/95) and a rat strain (1086C). In this study, we show that both strains productively infect primary human cardiomyocytes and induce complete cytolysis. Binding and infection inhibition experiments indicated that attachment and infection are independent of sialic acid and heparan sulfate for B279/95 and dependent for 1086C. Sequence comparison between the two strains and three-dimensional analysis of the capsid revealed that six of the seven variable residues are surfaceexposed, suggesting a role for these amino acids in binding. Moreover, analysis of variants isolated from the 1086C strain revealed the importance of lysine 231 of VP1 in the attachment of EMCV to cell-surface sialic acid residues. Together, these results show a potential for EMCV strains to use at least two different binding possibilities to initiate infection and provide new insights into the mechanisms involved in primary human cell recognition by EMCV.

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Analysis of sequence and pathogenic properties of two variants of encephalomyocarditis virus differing in a single amino acid in VP1

Cited by 27 publications

References 16 publications

Enterovirus infections with β‐cell tropic strains are frequent in siblings of children diagnosed with type 1 diabetes children and in association with elevated levels of GAD65 antibodies

Enterovirus infections with β‐cell tropic strains are frequent in siblings of children diagnosed with type 1 diabetes children and in association with elevated levels of GAD65 antibodies

A Wild-Type Porcine Encephalomyocarditis Virus Containing a Short Poly(C) Tract Is Pathogenic to Mice, Pigs, and Cynomolgus Macaques

Encephalomyocarditis virus may use different pathways to initiate infection of primary human cardiomyocytes

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