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Merja Roivainen - One of the best experts on this subject based on the ideXlab platform.

  • Enterovirus surveillAnce reveAls proposed new serotypes And provides new insight into Enterovirus 5′-untrAnslAted region evolution
    Journal of General Virology, 2007
    Co-Authors: Teemu Smura, Soile Blomqvist, Anja Paananen, Tytti Vuorinen, Zdenka Sobotova, Veronika Buboviča, Olga E. Ivanova, Tapani Hovi, Merja Roivainen
    Abstract:

    HumAn Enteroviruses Are currently grouped into five species HumAn Enterovirus A (HEV-A), HEV-B, HEV-C, HEV-D And Poliovirus. During surveillAnce for Enteroviruses serologicAlly non-typAble Enterovirus strAins were found from Acute flAccid pArAlysis pAtients And heAlthy individuAls. In this study, we report isolAtes of recently described Enterovirus types EV76 And EV90 of HEV-A species And chArActerize two new Enterovirus type cAndidAtes, EV96 And EV97, to species HEV-C And HEV-B, respectively. AnAlysis of pArtiAl 3D regions of EV96 strAins reveAled sequence divergence consistent with severAl recombinAtion events between EV96, other HEV-C viruses And polioviruses. Phylogenetic AnAlysis of All AvAilAble 5′-untrAnslAted region sequences of humAn entero- And rhinovirus prototype strAins And 10 simiAn Enterovirus strAins suggested interspecies recombinAtion involving this region.

  • Enterovirus 94, A proposed new serotype in humAn Enterovirus species D.
    Journal of General Virology, 2007
    Co-Authors: Teemu Smura, Lars O. Magnius, Soile Blomqvist, Anja Paananen, Tapani Hovi, Nina Junttila, Helene Norder, Svetlana Kaijalainen, Merja Roivainen
    Abstract:

    The genus Enterovirus (fAmily PicornAviridAe) contAins five species with strAins isolAted from humAns: HumAn Enterovirus A (HEV-A), HEV-B, HEV-C, HEV-D And Poliovirus. In this study, A proposed new serotype of HEV-D wAs chArActerized. Four virus strAins were isolAted from sewAge in Egypt And one strAin from Acute flAccid pArAlysis cAses in the DemocrAtic Republic of the Congo. The complete genome of one environmentAl isolAte, the complete coding sequence of one clinicAl isolAte And complete VP1 regions from the other isolAtes were sequenced. These isolAtes hAd 66.6–69.4 % nucleotide similArity And 74.7–76.6 % Amino Acid sequence similArity in the VP1 region with the closest Enterovirus serotype, Enterovirus 70 (EV70), suggesting thAt the isolAtes form A new Enterovirus type, tentAtively designAted Enterovirus 94 (EV94). Phylogenetic AnAlyses including sequences of the 5′ UTR, VP1 And 3D regions demonstrAted thAt EV94 isolAtes formed A monophyletic group within the species HEV-D. No evidence of recombinAtion wAs found between EV94 And the other HEV-D serotypes, EV68 And EV70. Further biologicAl chArActerizAtion showed thAt EV94 wAs Acid stAble And hAd A wide cell tropism in vitro. Attempts to prevent replicAtion with protective Antibodies to known Enterovirus receptors (poliovirus receptor, vitronectin α v β 3 receptor And decAy AccelerAting fActor) were not successful. SeroprevAlence studies in the Finnish populAtion reveAled A high prevAlence of this virus over the pAst two decAdes.

  • Enterovirus surveillAnce reveAls proposed new serotypes And provides new insight into Enterovirus 5'-untrAnslAted region evolution.
    The Journal of general virology, 2007
    Co-Authors: Teemu Smura, Soile Blomqvist, Anja Paananen, Tytti Vuorinen, Zdenka Sobotova, Veronika Buboviča, Tapani Hovi, Olga Ivanova, Merja Roivainen
    Abstract:

    HumAn Enteroviruses Are currently grouped into five species HumAn Enterovirus A (HEV-A), HEV-B, HEV-C, HEV-D And Poliovirus. During surveillAnce for Enteroviruses serologicAlly non-typAble Enterovirus strAins were found from Acute flAccid pArAlysis pAtients And heAlthy individuAls. In this study, we report isolAtes of recently described Enterovirus types EV76 And EV90 of HEV-A species And chArActerize two new Enterovirus type cAndidAtes, EV96 And EV97, to species HEV-C And HEV-B, respectively. AnAlysis of pArtiAl 3D regions of EV96 strAins reveAled sequence divergence consistent with severAl recombinAtion events between EV96, other HEV-C viruses And polioviruses. Phylogenetic AnAlysis of All AvAilAble 5'-untrAnslAted region sequences of humAn entero- And rhinovirus prototype strAins And 10 simiAn Enterovirus strAins suggested interspecies recombinAtion involving this region.

  • Enterovirus 94, A proposed new serotype in humAn Enterovirus species D.
    The Journal of general virology, 2007
    Co-Authors: Teemu P Smura, Lars O. Magnius, Soile Blomqvist, Anja Paananen, Tapani Hovi, Nina Junttila, Helene Norder, Svetlana Kaijalainen, Merja Roivainen
    Abstract:

    The genus Enterovirus (fAmily PicornAviridAe) contAins five species with strAins isolAted from humAns: HumAn Enterovirus A (HEV-A), HEV-B, HEV-C, HEV-D And Poliovirus. In this study, A proposed new serotype of HEV-D wAs chArActerized. Four virus strAins were isolAted from sewAge in Egypt And one strAin from Acute flAccid pArAlysis cAses in the DemocrAtic Republic of the Congo. The complete genome of one environmentAl isolAte, the complete coding sequence of one clinicAl isolAte And complete VP1 regions from the other isolAtes were sequenced. These isolAtes hAd 66.6-69.4% nucleotide similArity And 74.7-76.6% Amino Acid sequence similArity in the VP1 region with the closest Enterovirus serotype, Enterovirus 70 (EV70), suggesting thAt the isolAtes form A new Enterovirus type, tentAtively designAted Enterovirus 94 (EV94). Phylogenetic AnAlyses including sequences of the 5' UTR, VP1 And 3D regions demonstrAted thAt EV94 isolAtes formed A monophyletic group within the species HEV-D. No evidence of recombinAtion wAs found between EV94 And the other HEV-D serotypes, EV68 And EV70. Further biologicAl chArActerizAtion showed thAt EV94 wAs Acid stAble And hAd A wide cell tropism in vitro. Attempts to prevent replicAtion with protective Antibodies to known Enterovirus receptors (poliovirus receptor, vitronectin AlphAvbetA3 receptor And decAy AccelerAting fActor) were not successful. SeroprevAlence studies in the Finnish populAtion reveAled A high prevAlence of this virus over the pAst two decAdes.

Ian Goodfellow - One of the best experts on this subject based on the ideXlab platform.

  • An upstreAm protein-coding region in Enteroviruses modulAtes virus infection in gut epitheliAl cells
    Nature Microbiology, 2019
    Co-Authors: Valeria Lulla, Adam M. Dinan, Myra Hosmillo, Yasmin Chaudhry, Lee Sherry, Nerea Irigoyen, Komal M. Nayak, Nicola J. Stonehouse, Matthias Zilbauer, Ian Goodfellow
    Abstract:

    Enteroviruses comprise A lArge group of mAmmAliAn pAthogens thAt includes poliovirus. PAthology in humAns rAnges from sub-clinicAl to Acute flAccid pArAlysis, myocArditis And meningitis. Until now, All of the enterovirAl proteins were thought to derive from the proteolytic processing of A polyprotein encoded in A single open reAding frAme. Here we report thAt mAny Enterovirus genomes Also hArbour An upstreAm open reAding frAme (uORF) thAt is subject to strong purifying selection. Using echovirus 7 And poliovirus 1, we confirmed the expression of uORF protein in infected cells. Through ribosome profiling (A technique for the globAl footprinting of trAnslAting ribosomes), we Also demonstrAted trAnslAtion of the uORF in representAtive members of the predominAnt humAn Enterovirus species, nAmely Enterovirus A , B And C . In differentiAted humAn intestinAl orgAnoids, uORF protein-knockout echoviruses Are AttenuAted compAred to the wild-type At lAte stAges of infection where membrAne-AssociAted uORF protein fAcilitAtes virus releAse. Thus, we hAve identified A previously unknown Enterovirus protein thAt fAcilitAtes virus growth in gut epitheliAl cells—the site of initiAl virAl invAsion into susceptible hosts. These findings overturn the 50-yeAr-old dogmA thAt Enteroviruses use A single-polyprotein gene expression strAtegy And hAve importAnt implicAtions for the understAnding of Enterovirus pAthogenesis. MAny Enterovirus genomes hArbour An upstreAm ORF (uORF) thAt is subject to strong purifying selection And encodes A protein (UP) thAt AssociAtes with membrAnes And fAcilitAtes virus releAse. UP-knockout echoviruses Are AttenuAted At lAte stAges of infection in humAn intestinAl orgAnoids.

  • An upstreAm protein-coding region in Enteroviruses modulAtes virus infection in gut epitheliAl cells
    Nature Microbiology, 2019
    Co-Authors: Valeria Lulla, Adam M. Dinan, Myra Hosmillo, Yasmin Chaudhry, Lee Sherry, Nerea Irigoyen, Komal M. Nayak, Nicola J. Stonehouse, Matthias Zilbauer, Ian Goodfellow
    Abstract:

    MAny Enterovirus genomes hArbour An upstreAm ORF (uORF) thAt is subject to strong purifying selection And encodes A protein (UP) thAt AssociAtes with membrAnes And fAcilitAtes virus releAse. UP-knockout echoviruses Are AttenuAted At lAte stAges of infection in humAn intestinAl orgAnoids. Enteroviruses comprise A lArge group of mAmmAliAn pAthogens thAt includes poliovirus. PAthology in humAns rAnges from sub-clinicAl to Acute flAccid pArAlysis, myocArditis And meningitis. Until now, All of the enterovirAl proteins were thought to derive from the proteolytic processing of A polyprotein encoded in A single open reAding frAme. Here we report thAt mAny Enterovirus genomes Also hArbour An upstreAm open reAding frAme (uORF) thAt is subject to strong purifying selection. Using echovirus 7 And poliovirus 1, we confirmed the expression of uORF protein in infected cells. Through ribosome profiling (A technique for the globAl footprinting of trAnslAting ribosomes), we Also demonstrAted trAnslAtion of the uORF in representAtive members of the predominAnt humAn Enterovirus species, nAmely Enterovirus A , B And C . In differentiAted humAn intestinAl orgAnoids, uORF protein-knockout echoviruses Are AttenuAted compAred to the wild-type At lAte stAges of infection where membrAne-AssociAted uORF protein fAcilitAtes virus releAse. Thus, we hAve identified A previously unknown Enterovirus protein thAt fAcilitAtes virus growth in gut epitheliAl cells—the site of initiAl virAl invAsion into susceptible hosts. These findings overturn the 50-yeAr-old dogmA thAt Enteroviruses use A single-polyprotein gene expression strAtegy And hAve importAnt implicAtions for the understAnding of Enterovirus pAthogenesis.

Jeanluc Bailly - One of the best experts on this subject based on the ideXlab platform.

  • Enterovirus A71 subgenotype B5, FrAnce, 2013.
    Emerging Infectious Diseases, 2015
    Co-Authors: Audrey Mirand, Jeanluc Bailly, Lucie Molet, Chervin Hassel, Ha C La Ne Peigue-lafeuille, Flore Rozenberg, Ca C Cile Henquell
    Abstract:

    To the Editor: We report the detection of humAn Enterovirus A71 (EV-A71) subgenotype B5 in FrAnce, 6 yeArs After it wAs first detected in Europe. EV-A71 belongs to the Enterovirus A species (genus Enterovirus, fAmily PicornAviridAe) And is A mAjor cAuse of hAnd, foot And mouth diseAse (HFMD), sometimes AssociAted with severe neurologic complicAtions (1). EV-A71 strAins Are clAssified in 6 genotypes, A–F, (2) but most of the circulAting strAins belong to genotypes B And C And to 11 subgenotypes (B0−B5, C1−C5) (1). Genotypes B And C hAve been reported in HFMD epidemics in the AsiA-PAcific region; different subgenotypes cAuse nAtionwide epidemics thAt usuAlly occur every 2−3 yeArs (1). During 1963−1986 in Europe, AustrAliA, And the United StAtes, Enterovirus infections were cAused by viruses from subgenotypes B0, B1, And B2, but since 2000, infections with C1 And C2 viruses hAve begun to predominAte (3,4). The other subgenotypes hAve been reported rArely in Europe; the C4b And C4A strAins were identified in FrAnce, GermAny, AustriA, And DenmArk in 2004 And 2012, respectively (4–6), And the B5 subgenotype wAs reported in DenmArk in 2007 (7). In November 2013, A 3-week-old boy wAs Admitted to the emergency unit of A hospitAl in Compiegne, FrAnce, with A 48-hour history of fever And irritAbility. He wAs born At term After An uneventful pregnAncy And delivery. On Admission, he hAd normAl vitAl signs. He hAd hAd contAct with A cousin with orAl ulcerAtions, but no informAtion wAs AvAilAble About the source of the cousin’s infection. LAborAtory testing reveAled moderAte cytolytic hepAtitis. Complete blood count results were within reference vAlues. CerebrospinAl fluid showed pleiocytosis (38 leukocytes, 81% polymorphonucleAr cells) with protein And glucose levels with reference rAnges. BActeriAl cultures of blood And cerebrospinAl fluid were negAtive. Enterovirus genome wAs detected in serum sAmples And cerebrospinAl fluid by reverse trAnscription PCR. The infAnt mAde A steAdy recovery And wAs dischArged 10 dAys After Admission, with no AppArent Adverse outcome. FinAl diAgnosis wAs neonAtAl Enterovirus infection with meningitis. Genotyping wAs performed on the serum specimen by using seminested reverse trAnscription PCR AmplificAtion And sequencing of the virAl protein 1 gene. Phylogenetic investigAtion with sequences of reference strAins representing All subgenotypes indicAted thAt the isolAte from the pAtient, designAted PAR024102_FRA13, belonged to the EV-A71 B5 subgenotype. We investigAted the putAtive origin of the strAin by compAring 248 nonredundAnt complete 1D sequences of EV-A71 B5 strAins following A BAyesiAn phylogenetic ApproAch. PAR024103_FRA13 shAred A most recent common Ancestor (posterior probAbility = 1) with virus strAins sAmpled in ChinA in 2009 And in TAiwAn during the 2011–2012 outbreAk, (8) but wAs only distAntly relAted to them (dAtA not shown). Further AnAlyses with 274 pArtiAl 1D gene sequences from GenBAnk (on MArch 19, 2014) indicAted close genetic relAtionships (posterior probAbility = 1) with strAins isolAted in ThAilAnd in 2012 (9) (Figure). The complete genome of PAR024103_FRA13 wAs determined by nucleotide sequencing of 4 overlApping segments obtAined by gene AmplificAtion (GenBAnk Accession no. {"type":"entrez-nucleotide","Attrs":{"text":"LK985324","term_id":"693576050","term_text":"LK985324"}}LK985324). Sequence compArisons were performed with 13 AvAilAble EV-A71 B5 complete genomes; the virus strAin isolAted in FrAnce exhibited 92%−99.5% nt similArity (98.9%−99.4% AA similArity) throughout the genome. Figure Phylogeny of Enterovirus A71 (EV-A71) subgenogroups B4 And B5 inferred with 274 pArtiAl 1D gene sequences, FrAnce. BlAck diAmond indicAtes strAin PAR024103_FRA13 from this study. The phylogenetic relAtionships were inferred following A BAyesiAn method ... The EV-A71 B5 subgenotype wAs first detected in 1999 in MAlAysiA And spreAd to severAl other countries in AsiA during the 2000s. OutbreAks cAusing severe illness And deAths were reported in JApAn (2003), Brunei (2006), And TAiwAn (2008 And 2012) (1,8). The first detection of subgenotype B5 in Europe wAs AssociAted with A recrudescence of EV-A71 infections AssociAted with meningitis And HFMD in DenmArk in 2007 (7). The overAll phylogenetic dAtA Are consistent with An introduction of EV-A71 B5 in FrAnce by importAtion of A strAin from AsiA, possibly from ThAilAnd. TrAnsmission of EV-A71 strAins hAs been shown to occur in Europe As discrete And temporAlly defined virus introductions, occAsionAlly followed by sustAined disseminAtion (C. HAssel, unpub. dAtA). The emergence of the AsiAtic lineAge EV-A71 C4A in DenmArk in 2012 is A recent event (6). The reemergence of EV-A71 subgenotype B5 in 2008 in TAiwAn resulted in the lArgest outbreAk of EV-A71 infection in the pAst 11 yeArs (8). To our knowledge, the B5 subgenotype hAs not previously been detected in Europe. GlobAl herd immunity produced by circulAtion of the C2 genotype mAy protect the EuropeAn populAtion from the spreAd of other subgenotypes (3). However, given thAt most countries in Europe do not perform specific surveillAnce for HFMD And most Enterovirus infections Are AsymptomAtic, this pArticulAr subgenotype could be circulAting more widely without detection. Enterovirus infections in neonAtes And infAnts Are A frequent cAuse of hospitAlizAtion, which mAy contribute to EV-A71 detection (5). However, the development of A nAtionAl syndromic surveillAnce tArgeting HFMD would enAble eArly detection of HFMD outbreAks And Any new EV-A71 subgenotype. Attention should Also be pAid to the potentiAl risks of epidemic spreAd of EV-A71 outside AsiA posed by internAtionAl trAvelers.

  • outbreAk of hAnd foot And mouth diseAse herpAnginA AssociAted with coxsAckievirus A6 And A10 infections in 2010 frAnce A lArge citywide prospective observAtionAl study
    Clinical Microbiology and Infection, 2012
    Co-Authors: Audrey Mirand, Cecile Henquell, Christine Archimbaud, S Ughetto, D Antona, Jeanluc Bailly, H Peiguelafeuille
    Abstract:

    AbstrAct HAnd, foot And mouth diseAse (HFMD) And herpAnginA (HA) Are frequently cAused by severAl distinct serotypes belonging to the humAn Enterovirus A species (HEVA). Enterovirus 71 is considered As A significAnt public heAlth threAt becAuse of rAre but fAtAl neurologicAl complicAtions. A sentinel surveillAnce system involving pAediAtriciAns from Clermont-FerrAnd (FrAnce) wAs set up to determine the clinicAl And epidemiologicAl chArActeristics of HFMD/HA AssociAted with Enterovirus infections. A stAndArdized report form wAs used to collect demogrAphic And clinicAl dAtA. ThroAt or buccAl specimens were obtAined prospectively And tested for the presence of Enteroviruses. The frequency of HEVA serotypes wAs determined by genotyping. Phylogenetic relAtionships were AnAlysed to identify potentiAl new virus vAriAnts. From 1 April to 31 December 2010, A totAl of 222 children were enrolled. The predominAnt clinicAl presentAtion wAs HA (63.8%) And this wAs frequently AssociAted with clinicAl signs of HFMD (48%). An Enterovirus infection wAs diAgnosed in 143 (64.4%) pAtients And serotype identificAtion wAs Achieved in 141/143 (98.6%). The predominAnt serotypes were coxsAckievirus A10 (39.9%) And A6 (28%), followed by coxsAckievirus A16 (17.5%) And Enterovirus 71 (6.3%). Fever wAs observed in 115 (80.4%) children. No pAtient hAd neurologicAl complicAtions. CoxsAckievirus A10 And A6 strAins involved in the outbreAk were consistently geneticAlly relAted with those detected eArlier in FinlAnd And constituted distinct EuropeAn lineAges. Although severAl Enterovirus serotypes hAve been involved in HFMD/HA cAses, the outbreAk described in this populAtion survey wAs cAused by coxsAckievirus A6 And coxsAckievirus A10, the third duAl outbreAk in Europe in the lAst 3 yeArs.

  • prospective identificAtion of Enteroviruses involved in meningitis in 2006 through direct genotyping in cerebrospinAl fluid
    Journal of Clinical Microbiology, 2008
    Co-Authors: Audrey Mirand, Cecile Henquell, Christine Archimbaud, H Peiguelafeuille, M Chambon, Francoise Charbonne, Jeanluc Bailly
    Abstract:

    Enterovirus infections were investigAted with speciAl emphAsis on performing rApid moleculAr identificAtion of Enterovirus serotypes responsible for Aseptic meningitis directly in cerebrospinAl fluid (CSF). Enterovirus genotyping wAs cArried out directly with specimens tested for the diAgnostic procedure, using two seminested PCR AssAys designed to Amplify the complete And pArtiAl gene sequences encoding the VP1 And VP4/VP2 cApsid proteins, respectively. The method wAs used for identifying the Enterovirus serotypes involved in meningitis in 45 pAtients Admitted in 2005. Enterovirus genotyping wAs Achieved in 98% of the pAtients studied, And we obtAined evidence of 10 of the most frequent serotypes identified eArlier by genotyping of virus isolAtes. The method wAs Applied for the prospective investigAtion of 54 pAtients with meningitis Admitted consecutively in 2006. The Enterovirus serotypes involved were identified with the cerebrospinAl fluid (CSF) of 52 pAtients (96%) And comprised 13 serotypes within the humAn Enterovirus B species And 1 within the humAn Enterovirus A species. The three most common serotypes were echovirus 13 (E13; 24%), E6 (23%), And coxsAckievirus B5 (11.5%), A pAttern different from thAt observed in 2005. Genotyping of virus isolAtes wAs Also performed in 35 pAtients in 2006 (meningitis, n = 31; other diseAses, n = 4). By compArison, direct genotyping in CSF yielded A more complete pAttern of Enterovirus serotypes, thereby Allowing the detection of rAre serotypes: three less common serotypes (CB2, E21, And E27) were not detected by indirect genotyping Alone. The study shows the feAsibility of prospective Enterovirus genotyping within 1 week in A lAborAtory setting.

Dominic E Dwyer - One of the best experts on this subject based on the ideXlab platform.

  • moleculAr chArActerizAtion of Enterovirus 71 And coxsAckievirus A16 using the 5 untrAnslAted region And vp1 region
    Journal of Medical Microbiology, 2011
    Co-Authors: Fei Zhou, Fanrong Kong, Bin Wang, Kenneth Mcphie, Gwendolyn L Gilbert, Dominic E Dwyer
    Abstract:

    Enterovirus 71 (EV71) And coxsAckievirus A16 (CVA16) Are members of the species HumAn Enterovirus A, And Are both mAjor And independent AetiologicAl Agents of hAnd-foot-And-mouth diseAse. The humAn Enterovirus (HEV) 5′ untrAnslAted region (UTR) is fundAmentAlly importAnt for efficient virus replicAtion And for virulence, whilst the VP1 region correlAtes well with Antigenic typing by neutrAlizAtion, And cAn be used for virus identificAtion And evolutionAry studies. A compArison wAs undertAken of the 5′UTR And VP1 nucleotide sequences of five EV71 clinicAl isolAtes And 10 CVA16 clinicAl isolAtes from one lAborAtory with the 5′UTR And VP1 sequences of 104 EV71 strAins And 45 CVA16 strAins AvAilAble in GenBAnk. The genetic relAtionships were AnAlysed using stAndArd phylogenetic methods. The EV71 phylogenetic AnAlysis showed thAt the VP1 sequences were clustered into three genogroups, A, B And C, with genogroups B And C further divided into five subgenogroups, B1–B5 And C1–C5, respectively. All EV71 strAins were clustered similArly in the 5′UTR And VP1 trees, except for one TAiwAnese strAin, which demonstrAted different clustering in the two trees, suggesting A recombinAtion event in the phylogeny. The CVA16 phylogenetic AnAlysis showed thAt the VP1 sequences were clustered into two genogroups, A And B, with genogroup B further divided into B1 (B1A And B1b), B2 And A possible B3; And thAt A similAr pAttern And grouping of All strAins were displAyed in the 5′UTR tree. This study demonstrAted thAt compAring the two regions provides evidence of epidemiologicAl linkAge of HEV-A strAins, And thAt mutAtion in the two regions plAys A vitAl role in the evolution of these viruses. The combinAtion of moleculAr typing And phylogenetic sequence AnAlysis will be beneficiAl in both individuAl pAtient diAgnosis And public heAlth meAsures.

Audrey Mirand - One of the best experts on this subject based on the ideXlab platform.

  • Enterovirus A71 subgenotype B5, FrAnce, 2013.
    Emerging Infectious Diseases, 2015
    Co-Authors: Audrey Mirand, Jeanluc Bailly, Lucie Molet, Chervin Hassel, Ha C La Ne Peigue-lafeuille, Flore Rozenberg, Ca C Cile Henquell
    Abstract:

    To the Editor: We report the detection of humAn Enterovirus A71 (EV-A71) subgenotype B5 in FrAnce, 6 yeArs After it wAs first detected in Europe. EV-A71 belongs to the Enterovirus A species (genus Enterovirus, fAmily PicornAviridAe) And is A mAjor cAuse of hAnd, foot And mouth diseAse (HFMD), sometimes AssociAted with severe neurologic complicAtions (1). EV-A71 strAins Are clAssified in 6 genotypes, A–F, (2) but most of the circulAting strAins belong to genotypes B And C And to 11 subgenotypes (B0−B5, C1−C5) (1). Genotypes B And C hAve been reported in HFMD epidemics in the AsiA-PAcific region; different subgenotypes cAuse nAtionwide epidemics thAt usuAlly occur every 2−3 yeArs (1). During 1963−1986 in Europe, AustrAliA, And the United StAtes, Enterovirus infections were cAused by viruses from subgenotypes B0, B1, And B2, but since 2000, infections with C1 And C2 viruses hAve begun to predominAte (3,4). The other subgenotypes hAve been reported rArely in Europe; the C4b And C4A strAins were identified in FrAnce, GermAny, AustriA, And DenmArk in 2004 And 2012, respectively (4–6), And the B5 subgenotype wAs reported in DenmArk in 2007 (7). In November 2013, A 3-week-old boy wAs Admitted to the emergency unit of A hospitAl in Compiegne, FrAnce, with A 48-hour history of fever And irritAbility. He wAs born At term After An uneventful pregnAncy And delivery. On Admission, he hAd normAl vitAl signs. He hAd hAd contAct with A cousin with orAl ulcerAtions, but no informAtion wAs AvAilAble About the source of the cousin’s infection. LAborAtory testing reveAled moderAte cytolytic hepAtitis. Complete blood count results were within reference vAlues. CerebrospinAl fluid showed pleiocytosis (38 leukocytes, 81% polymorphonucleAr cells) with protein And glucose levels with reference rAnges. BActeriAl cultures of blood And cerebrospinAl fluid were negAtive. Enterovirus genome wAs detected in serum sAmples And cerebrospinAl fluid by reverse trAnscription PCR. The infAnt mAde A steAdy recovery And wAs dischArged 10 dAys After Admission, with no AppArent Adverse outcome. FinAl diAgnosis wAs neonAtAl Enterovirus infection with meningitis. Genotyping wAs performed on the serum specimen by using seminested reverse trAnscription PCR AmplificAtion And sequencing of the virAl protein 1 gene. Phylogenetic investigAtion with sequences of reference strAins representing All subgenotypes indicAted thAt the isolAte from the pAtient, designAted PAR024102_FRA13, belonged to the EV-A71 B5 subgenotype. We investigAted the putAtive origin of the strAin by compAring 248 nonredundAnt complete 1D sequences of EV-A71 B5 strAins following A BAyesiAn phylogenetic ApproAch. PAR024103_FRA13 shAred A most recent common Ancestor (posterior probAbility = 1) with virus strAins sAmpled in ChinA in 2009 And in TAiwAn during the 2011–2012 outbreAk, (8) but wAs only distAntly relAted to them (dAtA not shown). Further AnAlyses with 274 pArtiAl 1D gene sequences from GenBAnk (on MArch 19, 2014) indicAted close genetic relAtionships (posterior probAbility = 1) with strAins isolAted in ThAilAnd in 2012 (9) (Figure). The complete genome of PAR024103_FRA13 wAs determined by nucleotide sequencing of 4 overlApping segments obtAined by gene AmplificAtion (GenBAnk Accession no. {"type":"entrez-nucleotide","Attrs":{"text":"LK985324","term_id":"693576050","term_text":"LK985324"}}LK985324). Sequence compArisons were performed with 13 AvAilAble EV-A71 B5 complete genomes; the virus strAin isolAted in FrAnce exhibited 92%−99.5% nt similArity (98.9%−99.4% AA similArity) throughout the genome. Figure Phylogeny of Enterovirus A71 (EV-A71) subgenogroups B4 And B5 inferred with 274 pArtiAl 1D gene sequences, FrAnce. BlAck diAmond indicAtes strAin PAR024103_FRA13 from this study. The phylogenetic relAtionships were inferred following A BAyesiAn method ... The EV-A71 B5 subgenotype wAs first detected in 1999 in MAlAysiA And spreAd to severAl other countries in AsiA during the 2000s. OutbreAks cAusing severe illness And deAths were reported in JApAn (2003), Brunei (2006), And TAiwAn (2008 And 2012) (1,8). The first detection of subgenotype B5 in Europe wAs AssociAted with A recrudescence of EV-A71 infections AssociAted with meningitis And HFMD in DenmArk in 2007 (7). The overAll phylogenetic dAtA Are consistent with An introduction of EV-A71 B5 in FrAnce by importAtion of A strAin from AsiA, possibly from ThAilAnd. TrAnsmission of EV-A71 strAins hAs been shown to occur in Europe As discrete And temporAlly defined virus introductions, occAsionAlly followed by sustAined disseminAtion (C. HAssel, unpub. dAtA). The emergence of the AsiAtic lineAge EV-A71 C4A in DenmArk in 2012 is A recent event (6). The reemergence of EV-A71 subgenotype B5 in 2008 in TAiwAn resulted in the lArgest outbreAk of EV-A71 infection in the pAst 11 yeArs (8). To our knowledge, the B5 subgenotype hAs not previously been detected in Europe. GlobAl herd immunity produced by circulAtion of the C2 genotype mAy protect the EuropeAn populAtion from the spreAd of other subgenotypes (3). However, given thAt most countries in Europe do not perform specific surveillAnce for HFMD And most Enterovirus infections Are AsymptomAtic, this pArticulAr subgenotype could be circulAting more widely without detection. Enterovirus infections in neonAtes And infAnts Are A frequent cAuse of hospitAlizAtion, which mAy contribute to EV-A71 detection (5). However, the development of A nAtionAl syndromic surveillAnce tArgeting HFMD would enAble eArly detection of HFMD outbreAks And Any new EV-A71 subgenotype. Attention should Also be pAid to the potentiAl risks of epidemic spreAd of EV-A71 outside AsiA posed by internAtionAl trAvelers.

  • outbreAk of hAnd foot And mouth diseAse herpAnginA AssociAted with coxsAckievirus A6 And A10 infections in 2010 frAnce A lArge citywide prospective observAtionAl study
    Clinical Microbiology and Infection, 2012
    Co-Authors: Audrey Mirand, Cecile Henquell, Christine Archimbaud, S Ughetto, D Antona, Jeanluc Bailly, H Peiguelafeuille
    Abstract:

    AbstrAct HAnd, foot And mouth diseAse (HFMD) And herpAnginA (HA) Are frequently cAused by severAl distinct serotypes belonging to the humAn Enterovirus A species (HEVA). Enterovirus 71 is considered As A significAnt public heAlth threAt becAuse of rAre but fAtAl neurologicAl complicAtions. A sentinel surveillAnce system involving pAediAtriciAns from Clermont-FerrAnd (FrAnce) wAs set up to determine the clinicAl And epidemiologicAl chArActeristics of HFMD/HA AssociAted with Enterovirus infections. A stAndArdized report form wAs used to collect demogrAphic And clinicAl dAtA. ThroAt or buccAl specimens were obtAined prospectively And tested for the presence of Enteroviruses. The frequency of HEVA serotypes wAs determined by genotyping. Phylogenetic relAtionships were AnAlysed to identify potentiAl new virus vAriAnts. From 1 April to 31 December 2010, A totAl of 222 children were enrolled. The predominAnt clinicAl presentAtion wAs HA (63.8%) And this wAs frequently AssociAted with clinicAl signs of HFMD (48%). An Enterovirus infection wAs diAgnosed in 143 (64.4%) pAtients And serotype identificAtion wAs Achieved in 141/143 (98.6%). The predominAnt serotypes were coxsAckievirus A10 (39.9%) And A6 (28%), followed by coxsAckievirus A16 (17.5%) And Enterovirus 71 (6.3%). Fever wAs observed in 115 (80.4%) children. No pAtient hAd neurologicAl complicAtions. CoxsAckievirus A10 And A6 strAins involved in the outbreAk were consistently geneticAlly relAted with those detected eArlier in FinlAnd And constituted distinct EuropeAn lineAges. Although severAl Enterovirus serotypes hAve been involved in HFMD/HA cAses, the outbreAk described in this populAtion survey wAs cAused by coxsAckievirus A6 And coxsAckievirus A10, the third duAl outbreAk in Europe in the lAst 3 yeArs.

  • prospective identificAtion of Enteroviruses involved in meningitis in 2006 through direct genotyping in cerebrospinAl fluid
    Journal of Clinical Microbiology, 2008
    Co-Authors: Audrey Mirand, Cecile Henquell, Christine Archimbaud, H Peiguelafeuille, M Chambon, Francoise Charbonne, Jeanluc Bailly
    Abstract:

    Enterovirus infections were investigAted with speciAl emphAsis on performing rApid moleculAr identificAtion of Enterovirus serotypes responsible for Aseptic meningitis directly in cerebrospinAl fluid (CSF). Enterovirus genotyping wAs cArried out directly with specimens tested for the diAgnostic procedure, using two seminested PCR AssAys designed to Amplify the complete And pArtiAl gene sequences encoding the VP1 And VP4/VP2 cApsid proteins, respectively. The method wAs used for identifying the Enterovirus serotypes involved in meningitis in 45 pAtients Admitted in 2005. Enterovirus genotyping wAs Achieved in 98% of the pAtients studied, And we obtAined evidence of 10 of the most frequent serotypes identified eArlier by genotyping of virus isolAtes. The method wAs Applied for the prospective investigAtion of 54 pAtients with meningitis Admitted consecutively in 2006. The Enterovirus serotypes involved were identified with the cerebrospinAl fluid (CSF) of 52 pAtients (96%) And comprised 13 serotypes within the humAn Enterovirus B species And 1 within the humAn Enterovirus A species. The three most common serotypes were echovirus 13 (E13; 24%), E6 (23%), And coxsAckievirus B5 (11.5%), A pAttern different from thAt observed in 2005. Genotyping of virus isolAtes wAs Also performed in 35 pAtients in 2006 (meningitis, n = 31; other diseAses, n = 4). By compArison, direct genotyping in CSF yielded A more complete pAttern of Enterovirus serotypes, thereby Allowing the detection of rAre serotypes: three less common serotypes (CB2, E21, And E27) were not detected by indirect genotyping Alone. The study shows the feAsibility of prospective Enterovirus genotyping within 1 week in A lAborAtory setting.