Emergence of enterovirus D68 in Denmark, June 2014 to February 2015

Midgley, Sofie; Christiansen, Claus; Poulsen, Mille Weismann; Hansen, Christoffer Holst; Fischer, T K

doi:10.2807/1560-7917.es2015.20.17.21105

Cited by 53 publications

(46 citation statements)

References 16 publications

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“…One of the most striking features of the 2014 outbreak was that most EV-D68 infections were associated with severe respiratory diseases in children (36,40,41,(60)(61)(62)(63)(64)(65)69). However, we found no association between age, gender, or clinical symptoms and different viral subclades in our Kansas City population.…”

Section: Discussioncontrasting

confidence: 53%

“…During the 2014 outbreak, a novel subclade, B1, seems to have rapidly emerged and was dominant during the U.S. outbreak (38,60,61). During the same period, subclades A1 and B2 continued to be isolated in European countries (40,41,(62)(63)(64)(65). In addition, we found multiple viral introductions from other localities into the single locality of Kansas City during the 2014 U.S. outbreak despite the relatively small number of sequences collected (60), indicating that EV-D68 exhibits relatively fluid spatial dynamics within the United States.…”

Section: Discussionmentioning

confidence: 96%

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Molecular Evolution and Intraclade Recombination of Enterovirus D68 during the 2014 Outbreak in the United States

Tan

Hassan

Schuster

et al. 2016

J Virol

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In August 2014, an outbreak of enterovirus D68 (EV-D68) occurred in North America, causing severe respiratory disease in children. Due to a lack of complete genome sequence data, there is only a limited understanding of the molecular evolution and epidemiology of EV-D68 during this outbreak, and it is uncertain whether the differing clinical manifestations of EV-D68 infection are associated with specific viral lineages. We developed a high-throughput complete genome sequencing pipeline for EV-D68 that produced a total of 59 complete genomes from respiratory samples with a 95% success rate, including 57 genomes from Kansas City, MO, collected during the 2014 outbreak. With these data in hand, we performed phylogenetic analyses of complete genome and VP1 capsid protein sequences. Notably, we observed considerable genetic diversity among EV-D68 isolates in Kansas City, manifest as phylogenetically distinct lineages, indicative of multiple introductions of this virus into the city. In addition, we identified an intersubclade recombination event within EV-D68, the first recombinant in this virus reported to date. Finally, we found no significant association between EV-D68 genetic variation, either lineages or individual mutations, and a variety of demographic and clinical variables, suggesting that host factors likely play a major role in determining disease severity. Overall, our study revealed the complex pattern of viral evolution within a single geographic locality during a single outbreak, which has implications for the design of effective intervention and prevention strategies. IMPORTANCEUntil recently, EV-D68 was considered to be an uncommon human pathogen, associated with mild respiratory illness. However, in 2014 EV-D68 was responsible for more than 1,000 disease cases in North America, including severe respiratory illness in children and acute flaccid myelitis, raising concerns about its potential impact on public health. Despite the emergence of EV-D68, a lack of full-length genome sequences means that little is known about the molecular evolution of this virus within a single geographic locality during a single outbreak. Here, we doubled the number of publicly available complete genome sequences of EV-D68 by performing high-throughput next-generation sequencing, characterized the evolutionary history of this outbreak in detail, identified a recombination event, and investigated whether there was any correlation between the demographic and clinical characteristics of the patients and the viral variant that infected them. Overall, these results will help inform the design of intervention strategies for EV-D68.

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Section: Discussioncontrasting

confidence: 53%

Section: Discussionmentioning

confidence: 96%

Molecular Evolution and Intraclade Recombination of Enterovirus D68 during the 2014 Outbreak in the United States

Tan

Hassan

Schuster

et al. 2016

J Virol

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“…Our study examined the prevalence of EV-D68 in Thailand in children of less than 5 years of age, as they appeared to be the most vulnerable to infection (13). The EV-D68 prevalence of 0.6z found in Thailand between 2012 and 2014 (and 0.8z overall) is lower than the rates reported in Europe in recent years: 7.7z in Germany (24), 2z in the Netherlands (16), 17z in Norway (14), and 11z in Denmark (15). Our data suggest that the prevalence of EV-D68 in Thailand varies annually between 0-4.3z (mean ＝ 1.5z) and slightly above the 0.45z found in China (7) and 0.87z in Japan (11).…”

contrasting

confidence: 41%

“…A large outbreak in the United States and Canada in 2014 affected many more than the 1,100 laboratory-confirmed cases (13). Recently, reports of EV-D68 infections have continued to appear in Europe including in Norway (14), Denmark (15), and the Netherlands (16).…”

mentioning

confidence: 99%

Prevalence and Phylogenetic Characterization of Enterovirus D68 in Pediatric Patients with Acute Respiratory Tract Infection in Thailand

et al. 2016

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SUMMARY: Enterovirus D68 (EV-D68) is associated with severe lower respiratory tract infection and neurological abnormalities including acute myelitis and cranial nerve dysfunction. To determine whether an increased incidence of EV-D68 occurs in Southeast Asia, we retrospectively tested specimens collected from Thai pediatric patients who were less than 5 years of age and presented with acute respiratory tract infections between 2012 and 2014. Reverse transcription-polymerase chain reaction and nucleotide sequencing of the 5 ? -UTR/VP2 region were used to identify EV-D68. We also examined the epidemiological pattern of EV-D68 since 2009, when it was first identified in Thailand, and compiled records of clinical manifestations in children with confirmed EV-D68 infection. From 837 samples, 5 samples (0.6z) tested positive for EV-D68. All patients presented with viral pneumonia and required hospitalization. Phylogenetic analysis of the VP4/VP2 regions revealed that EV-D68 strains circulating in Thailand between 2012 and 2014 were closely related to strains reported in Japan, United Kingdom, China, and France. Continued surveillance of probable EV-D68-associated severe respiratory tract infection and the development of a rapid diagnostic test for EV-D68 are essential in supporting awareness and facilitating disease prevention and control.Enterovirus D68 (EV-D68) is a subtype of Enterovirus enterovirus D within the family Picornaviridae. It was first isolated in the United States in 1962 from respiratory specimens obtained from 4 pediatric patients with pneumonia and bronchiolitis (1). Since then, EV-D68 infections have occurred in small numbers and accounted for only 26 reports among enteroviruses detected in the United States during the 36-year surveillance period from 1970-2005 (2). Between 2008-2010, clusters of EV-D68 emerged in the Philippines, Japan, the Netherlands, and the United States (3). EV-D68 infections have

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“…A global upsurge of EV-D68 infections in patients with respiratory tract infections (RTIs) has been observed in recent years (2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21). In 2014, a large outbreak of EV-D68 infections occurred in the United States, which raised public health concern owing to severe respiratory illness and neurological complications (22)(23)(24)(25)(26)(27)(28)(29)(30).…”

mentioning

confidence: 99%

3C Protease of Enterovirus D68 Inhibits Cellular Defense Mediated by Interferon Regulatory Factor 7

Zou

Liu

Lei

et al. 2016

J Virol

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Human enterovirus 68 (EV-D68) is a member of the EV-D species, which belongs to the EV genus of the Picornaviridae family.Over the past several years, clusters of EV-D68 infections have occurred worldwide. A recent outbreak in the United States is the largest one associated with severe respiratory illness and neurological complication. Although clinical symptoms are recognized, the virus remains poorly understood. Here we report that EV-D68 inhibits innate antiviral immunity by downregulation of interferon regulatory factor 7 (IRF7), an immune factor with a pivotal role in viral pathogenesis. This process depends on 3C pro , an EV-D68-encoded protease, to mediate IRF7 cleavage. When expressed in host cells, 3C pro targets Q167 and Q189 within the constitutive activation domain, resulting in cleavage of IRF7. Accordingly, wild-type IRF7 is fully active. However, IRF7 cleavage abrogated its capacity to activate type I interferon expression and limit replication of EV-D68. Notably, IRF7 cleavage strictly requires the protease activity of 3C pro . Together, these results suggest that a dynamic interplay between 3C pro and IRF7 may determine the outcome of EV-D68 infection. IMPORTANCE EV-D68 is a globally emerging pathogen, but the molecular basis of EV-D68 pathogenesis is unclear. Here we report that EV-D68 inhibits innate immune responses by targeting an immune factor, IRF7. This involves the 3C protease encoded by EV-D68, which mediates the cleavage of IRF7. These observations suggest that the 3C pro -IRF7 interaction may represent an interface that dictates EV-D68 infection.E nterovirus D68 (EV-D68) was first isolated from children with lower respiratory tract infections in California, USA, in 1962 and belongs to the species Enterovirus D within the Enterovirus genus, Picornaviridae (1). A global upsurge of EV-D68 infections in patients with respiratory tract infections (RTIs) has been observed in recent years (2-21). In 2014, a large outbreak of EV-D68 infections occurred in the United States, which raised public health concern owing to severe respiratory illness and neurological complications (22)(23)(24)(25)(26)(27)(28)(29)(30).Although linked to clinical disease, EV-D68 remains poorly characterized. EV-D68 is structurally similar to other enteroviruses (31). The virus possesses a genome approximately 7.4 kb in size, with the capacity to encode a large precursor that is processed into structural proteins (VP1, VP2, VP3, and VP4) and nonstructural proteins (2A, 2B, 2C, 3A, 3B, 3C, and 3D) (17). Viral infection initiates with sialic acids of the epithelial cells (32). In this process, the virus preferentially binds to ␣2,6-linked sialic acids rather than to ␣2,3-linked sialic acids (33). In addition, EV-D68 is able to infect leukocyte cells (34). As such, active replication of EV-D68 is thought to trigger cytokine responses (35).It is well established that the pattern-recognition receptors (PRRs) initiate innate antiviral immunity through activation of interferon regulatory factor 3 (IRF3), interferon r...

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Emergence of enterovirus D68 in Denmark, June 2014 to February 2015

Abstract: Binary file ES_Abstracts_Final_ECDC.txt matches

Cited by 53 publications

References 16 publications

Molecular Evolution and Intraclade Recombination of Enterovirus D68 during the 2014 Outbreak in the United States

Molecular Evolution and Intraclade Recombination of Enterovirus D68 during the 2014 Outbreak in the United States

Prevalence and Phylogenetic Characterization of Enterovirus D68 in Pediatric Patients with Acute Respiratory Tract Infection in Thailand

3C Protease of Enterovirus D68 Inhibits Cellular Defense Mediated by Interferon Regulatory Factor 7

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