Nearly Complete Genome Sequences of 17 Enterovirus D68 Strains from Kansas City, Missouri, 2018

Pakala, Suman B.; Tan, Yi; Hassan, Ferdaus; Mai, Annie; Markowitz, Robert H George; Shilts, Meghan H.; Rajagopala, Seesandra V.; Selvarangan, Rangaraj; Das, Suman

doi:10.1128/mra.00388-19

Cited by 6 publications

(6 citation statements)

References 16 publications

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“…On the other hand, phylogenetic analyses suggested rapid evolution of EV-D68 (14,15,(36)(37)(38)(39). In particular, a recent analysis suggests a possibility of antigenic evolution of EV-D68 and reinfection of adults with A1 and A2 subclades (39).…”

Section: Discussionmentioning

confidence: 99%

“…The possibility that the historical strains are likely to have been maintained in various cell cultures for decades, a condition that is known to select for different phenotypes and is often used to create attenuated strains (35), adds further uncertainty to the differences in neurovirulence between historical and contemporary strains. Although rapid evolution of EV-D68 at the population level, including the possibility of antigenic evolution, has been previously suggested (14,15,(36)(37)(38)(39), it is unclear whether the evolution of EV-D68 is associated with the recent emergence of AFM.…”

Section: Spatiotemporal Association Between Ev-d68 and Afmmentioning

confidence: 99%

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Epidemiological dynamics of enterovirus D68 in the United States and implications for acute flaccid myelitis

et al. 2021

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Acute flaccid myelitis (AFM) recently emerged in the United States as a rare but serious neurological condition since 2012. Enterovirus D68 (EV-D68) is thought to be a main causative agent, but limited surveillance of EV-D68 in the United States has hampered the ability to assess their causal relationship. Using surveillance data from the BioFire Syndromic Trends epidemiology network in the United States from January 2014 to September 2019, we characterized the epidemiological dynamics of EV-D68 and found latitudinal gradient in the mean timing of EV-D68 cases, which are likely climate driven. We also demonstrated a strong spatiotemporal association of EV-D68 with AFM. Mathematical modeling suggested that the recent dominant biennial cycles of EV-D68 dynamics may not be stable. Nonetheless, we predicted that a major EV-D68 outbreak, and hence an AFM outbreak, would have still been possible in 2020 under normal epidemiological conditions. Nonpharmaceutical intervention efforts due to the ongoing COVID-19 pandemic are likely to have reduced the sizes of EV-D68 and AFM outbreaks in 2020, illustrating the broader epidemiological impact of the pandemic.

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Section: Discussionmentioning

confidence: 99%

Section: Spatiotemporal Association Between Ev-d68 and Afmmentioning

confidence: 99%

Epidemiological dynamics of enterovirus D68 in the United States and implications for acute flaccid myelitis

et al. 2021

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“…Also, more than one-third (57 of 160, 35.6%) of our cases in 2016 were from patient specimens collected in June and July. Frequently, such specimens may not be selected and subsequently examined for EV-D68 (15,21,31,32). It is unclear whether such a selection bias contributed to dissociation in the number of EV-68 and AFM cases reported in the US in 2016 (7,33).…”

Section: Resultsmentioning

confidence: 99%

Biennial Upsurge and Molecular Epidemiology of Enterovirus D68 Infection in New York, USA, 2014 to 2018

et al. 2020

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Enterovirus D68 (EV-D68) infection has been associated with outbreaks of severe respiratory illness and increased cases of non-polio acute flaccid myelitis. The patterns of EV-D68 circulation and molecular epidemiology are not fully understood. In this study nasopharyngeal (NP) specimens collected from patients in the Lower Hudson Valley, New York from 2014 to 2018 were examined for Rhinovirus/Enterovirus (RhV/EV) by the FilmArray Respiratory Panel. Selected RhV/EV-positive NP specimens were analyzed using two EV-D68-specific real-time RT-PCR assays, Sanger sequencing and metatranscriptomic next-generation sequencing. A total of 2,398 NP specimens were examined. EV-D68 was detected in 348 patients with NP specimens collected in 2014 (n=94), 2015 (n=0), 2016 (n=160), 2017 (n=5) and 2018 (n=89), demonstrating a biennial upsurge of EV-D68 infection in the study area. Ninety-one complete or nearly complete EV-D68 genome sequences were obtained. Genomic analysis of these EV-D68 strains revealed dynamics and evolution of circulating EV-D68 strains since 2014. The dominant EV-D68 strains causing the 2014 outbreak belonged to subclade B1, with a few belonging to subclade B2. New EV-D68 subclade B3 strains emerged in 2016 and continued in circulation in 2018. Clade D strains that are rarely detected in the US also arose and spread in 2018. The establishment of distinct viral strains and their variable circulation patterns provides essential information for future surveillance, diagnosis, vaccine development, and prediction of EV-D68-associated disease prevalence and potential outbreaks.

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“…Between 1970 and 2005, only 26 cases were reported to the CDC and the virus was generally associated with mild upper respiratory illness [8,9].In 2014, unprecedented outbreaks of EV-D68 associated with severe respiratory disease and acute flaccid myelitis emerged throughout the world [3,. Since 2014, there have been biannual patterns of severe disease associated with EV-D68 [31][32][33][34][35][36][37][38][39][40][41][42][43][44][45][46][47][48][49][50]. This unique pattern of recurring outbreaks and severe pathology sheds light on the importance of understanding evolutionary changes in contemporary EV-D68 strains.…”

Section: Introductionmentioning

confidence: 99%

Contemporary Enterovirus D68 strains show enhanced replication and translation at 37°C

Smith

Pekosz

2020

Preprint

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Enterovirus D68 (EV-D68) emerged in 2014 as an important pathogen linked to severe lower respiratory disease and acute flaccid myelitis outbreaks. Historically associated with mild common-cold-like symptoms, clusters of severe disease attributed to EV-D68 appeared during a series of outbreaks in 2014, 2016, and 2018. Previous studies of historic EV-D68 strains demonstrated attenuated replication at temperatures of the lower respiratory tract (37°C), when compared to the upper respiratory tract (32°C). By testing a panel of historic and contemporary EV-D68 strains at 32°C and 37°C, we demonstrate that contemporary strains of EV-D68 undergo little to no attenuation at increased temperatures. Contemporary strains produced higher levels of viral proteins at 32°C and 37°C than historic strains, although both strains infected similar numbers of cells and had comparable amounts of replication complexes. IRES activity assays with dual-luciferase reporter plasmids demonstrated enhanced translation in recent EV-D68 strains mapped to regions of variability in the 5' UTR found only in contemporary strains. Using an infectious clone system, we demonstrate that the translation advantage dictated by the 5' UTR does not solely mediate temperature sensitivity. The strain-dependent effects of temperature on the EV-D68 life cycle gives insight into the susceptibility of the lower respiratory system to contemporary strains. IMPORTANCEEnterovirus-D68 (EV-D68) emerged in 2014 as a causative agent of biannual severe pediatric respiratory disease and acute flaccid myelitis (AFM). We show that recent EV-D68 viruses have gained the ability to replicate at 37⁰C. Enhanced virus protein translation seemed to correlate with enhanced virus replication at 37⁰C but other genetic factors are also contributing to this phenotype. An enhanced ability to replicate at core body temperature may have allowed EV-D68 to penetrate both lower in the respiratory tract and into the central nervous system, explaining the recent surge in severe disease associated with virus infection.

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Nearly Complete Genome Sequences of 17 Enterovirus D68 Strains from Kansas City, Missouri, 2018

Cited by 6 publications

References 16 publications

Epidemiological dynamics of enterovirus D68 in the United States and implications for acute flaccid myelitis

Epidemiological dynamics of enterovirus D68 in the United States and implications for acute flaccid myelitis

Biennial Upsurge and Molecular Epidemiology of Enterovirus D68 Infection in New York, USA, 2014 to 2018

Contemporary Enterovirus D68 strains show enhanced replication and translation at 37°C

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