Increased Activity of Coxsackievirus B1 Strains Associated with Severe Disease among Young Infants in the United States, 2007–2008

Wikswo, Mary E.; Khetsuriani, Nino; Fowlkes, Ashley; Zheng, Xiaotian; Peñaranda, Silvia; Verma, Natasha; Shulman, Stanford T.; Sircar, Kanta; Robinson, Christine C.; Schmidt, Terry; Schnurr, David P.; Oberste, M. Steven

doi:10.1086/605090

Cited by 77 publications

(49 citation statements)

References 31 publications

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“…Therefore, prospective studies are needed to confirm the risk effect of CVB infections and to evaluate their etiologic fraction. In any case, the present observations together with previous studies showing that CVB1 infection is frequent (31) and able to cause insulitis and islet cell damage in young babies (32) as well as pancreatitis, transient diabetes (33,34), and persisting infection in mice (2) make it an attractive target for further studies addressing the possible role of EVs in the pathogenesis of type 1 diabetes. Author Contributions.…”

Section: Discussionsupporting

confidence: 62%

Virus Antibody Survey in Different European Populations Indicates Risk Association Between Coxsackievirus B1 and Type 1 Diabetes

et al. 2014

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Enteroviruses (EVs) have been connected to type 1 diabetes in various studies. The current study evaluates the association between specific EV subtypes and type 1 diabetes by measuring typespecific antibodies against the group B coxsackieviruses (CVBs), which have been linked to diabetes in previous surveys. Altogether, 249 children with newly diagnosed type 1 diabetes and 249 control children matched according to sampling time, sex, age, and country were recruited in Finland, Sweden, England, France, and Greece between 2001 and 2005 (mean age 9 years; 55% male). Antibodies against CVB1 were more frequent among diabetic children than among control children (odds ratio 1.7 [95% CI 1.0-2.9]), whereas other CVB types did not differ between the groups. CVB1-associated risk was not related to HLA genotype, age, or sex. Finnish children had a lower frequency of CVB antibodies than children in other countries. The results support previous studies that suggested an association between CVBs and type 1 diabetes, highlighting the possible role of CVB1 as a diabetogenic virus type. A connection between enterovirus (EV) infections and human type 1 diabetes has been documented in a variety of studies (1-3). Meta-analyses of studies on direct detection of EVs in blood or tissues have indicated a clear risk effect (odds ratios [ORs] 5.5-17.4) (4), whereas serological studies have shown inconsistent results (5). Accordingly, invasive infection, as reflected by the presence of EV in blood or tissues, rather than superficial

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Section: Discussionsupporting

confidence: 62%

Virus Antibody Survey in Different European Populations Indicates Risk Association Between Coxsackievirus B1 and Type 1 Diabetes

et al. 2014

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“…The earliest coxsackievirus B strains were isolated in the 1940s and 1950s in children with symptoms of acute meningitis or paralytic poliomyelitis (24) and were classified into six types, CVB1 to CVB6, as members of the enterovirus B species (9). Coxsackievirus B infections are associated with severe neurological manifestations and are involved in acute myocarditis and fatal neonatal infections (24,25). CVB5 is frequent in virus isolation records, as it consistently appears in the top five commonly identified EV types in the United States and France (13,14) and has exhibited the highest annual prevalence in a number of countries (26,27).…”

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confidence: 99%

Phylogenetic Patterns of Human Coxsackievirus B5 Arise from Population Dynamics between Two Genogroups and Reveal Evolutionary Factors of Molecular Adaptation and Transmission

Henquell

Mirand

Richter

et al. 2013

J Virol

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The aim of this study was to gain insights into the tempo and mode of the evolutionary processes that sustain genetic diversity in coxsackievirus B5 (CVB5) and into the interplay with virus transmission. We estimated phylodynamic patterns with a large sample of virus strains collected in Europe by Bayesian statistical methods, reconstructed the ancestral states of genealogical nodes, and tested for selection. The genealogies estimated with the structural one-dimensional gene encoding the VP1 protein and nonstructural 3CD locus allowed the precise description of lineages over time and cocirculating virus populations within the two CVB5 clades, genogroups A and B. Strong negative selection shaped the evolution of both loci, but compelling phylogenetic data suggested that immune selection pressure resulted in the emergence of the two genogroups with opposed evolutionary pathways. The genogroups also differed in the temporal occurrence of the amino acid changes. The virus strains of genogroup A were characterized by sequential acquisition of nonsynonymous changes in residues exposed at the virus 5-fold axis. The genogroup B viruses were marked by selection of three changes in a different domain (VP1 C terminus) during its early emergence. These external changes resulted in a selective sweep, which was followed by an evolutionary stasis that is still ongoing after 50 years. The inferred population history of CVB5 showed an alternation of the prevailing genogroup during meningitis epidemics across Europe and is interpreted to be a consequence of partial cross-immunity.

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“…CVB1 was initially isolated in 1948 near Coxsackie, NY, but a new variant of CVB1 emerged in 2007 and was detected at nearly 50 sites in the United States. Large clusters of cases occurred in Chicago, IL, and Los Angeles, CA, including cases of sepsis, myocarditis, and deaths among newborns (6,42,45). Since then, CVB1 has been the most commonly identified enterovirus in the United States (7).…”

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confidence: 99%

Fluoxetine Is a Potent Inhibitor of Coxsackievirus Replication

Zuo

Quinn²,

Kye³

et al. 2012

Antimicrob Agents Chemother

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ABSTRACTNo antiviral drugs currently exist for the treatment of enterovirus infections, which are often severe and potentially life threatening. Molecular screening of small molecule libraries identified fluoxetine, a selective serotonin reuptake inhibitor, as a potent inhibitor of coxsackievirus replication. Fluoxetine did not interfere with either viral entry or translation of the viral genome. Instead, fluoxetine and its metabolite norfluoxetine markedly reduced the synthesis of viral RNA and protein. In view of its favorable pharmacokinetics and safety profile, fluoxetine warrants additional study as a potential antiviral agent for enterovirus infections.

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Increased Activity of Coxsackievirus B1 Strains Associated with Severe Disease among Young Infants in the United States, 2007–2008

Abstract: Healthcare providers and public health departments should be vigilant to the possibility of continuing CVB1-associated neonatal illness, and testing and continued reporting of enterovirus infections should be encouraged.

Cited by 77 publications

References 31 publications

Virus Antibody Survey in Different European Populations Indicates Risk Association Between Coxsackievirus B1 and Type 1 Diabetes

Virus Antibody Survey in Different European Populations Indicates Risk Association Between Coxsackievirus B1 and Type 1 Diabetes

Phylogenetic Patterns of Human Coxsackievirus B5 Arise from Population Dynamics between Two Genogroups and Reveal Evolutionary Factors of Molecular Adaptation and Transmission

Fluoxetine Is a Potent Inhibitor of Coxsackievirus Replication

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