Noroviruses: The Most Common Pediatric Viral Enteric Pathogen at a Large University Hospital After Introduction of Rotavirus Vaccination

Koo, Hoonmo L.; Neill, Frederick H.; Estes, Mary K.; Muñoz, Flor M.; Cameron, Arlin G.; DuPont, Herbert L.; Atmar, Robert L.

doi:10.1093/jpids/pis070

Cited by 156 publications

(135 citation statements)

References 9 publications

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“…Our NGS data did not reveal the presence of norovirus, a leading cause of pediatric gastroenteritis (69,70,77,78), in any of the neonatal stool samples analyzed in this study. This finding was unexpected given an earlier surveillance study indicating that a third of all norovirus-infected Vellore neonates with GI disease were coinfected with RV (79).…”

Section: Discussioncontrasting

confidence: 63%

Absence of Genetic Differences among G10P[11] Rotaviruses Associated with Asymptomatic and Symptomatic Neonatal Infections in Vellore, India

Libonati

Dennis

Ramani

et al. 2014

J Virol

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Rotaviruses (RVs) are leading causes of severe diarrhea and vomiting in infants and young children. RVs with G10P[11] genotype specificity have been associated with symptomatic and asymptomatic neonatal infections in Vellore, India. To identify possible viral genetic determinants responsible for differences in symptomology, the genome sequences of G10P[11] RVs in stool samples of 19 neonates with symptomatic infections and 20 neonates with asymptomatic infections were determined by Sanger and next-generation sequencing. The data showed that all 39 viruses had identical genotype constellations (G10-P[11]-I2-R2-C2-M2-A1-N1-T1-E2-H3), the same as those of the previously characterized symptomatic N155 Vellore isolate. The data also showed that the RNA and deduced protein sequences of all the Vellore G10P[11] viruses were nearly identical; no nucleotide or amino acid differences were found that correlated with symptomatic versus asymptomatic infection. Next-generation sequencing data revealed that some stool samples, both from neonates with symptomatic infections and from neonates with asymptomatic infections, also contained one or more positive-strand RNA viruses (Aichi virus, astrovirus, or salivirus/klassevirus) suspected of being potential causes of pediatric gastroenteritis. However, none of the positive-strand RNA viruses could be causally associated with the development of symptoms. These results indicate that the diversity of clinical symptoms in Vellore neonates does not result from genetic differences among G10P[11] RVs; instead, other undefined factors appear to influence whether neonates develop gastrointestinal disease symptoms. IMPORTANCERotavirus (RV) strains have been identified that preferentially replicate in neonates, in some cases, without causing gastrointestinal disease. Surveillance studies have established that G10P[11] RVs are a major cause of neonatal infection in Vellore, India, with half of infected neonates exhibiting symptoms. We used Sanger and next-generation sequencing technologies to contrast G10P[11] RVs recovered from symptomatic and asymptomatic neonates. Remarkably, the data showed that the RNA genomes of the viruses were virtually indistinguishable and lacked any differences that could explain the diversity of clinical outcomes among infected Vellore neonates. The sequencing results also indicated that some symptomatic and some asymptomatic Vellore neonates were infected with other enteric viruses (Aichi virus, astrovirus, salvirus/klassevirus); however, none could be correlated with the presence of symptoms in neonates. Together, our findings suggest that other poorly defined factors, not connected to the genetic makeup of the Vellore G10P[11] viruses, influence whether neonates develop gastrointestinal disease symptoms.

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Section: Discussioncontrasting

confidence: 63%

Absence of Genetic Differences among G10P[11] Rotaviruses Associated with Asymptomatic and Symptomatic Neonatal Infections in Vellore, India

Libonati

Dennis

Ramani

et al. 2014

J Virol

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“…The TCH-060 strain of NoV used in our studies was isolated from an 11-year-old boy in 2003 at the Texas Children's Hospital, Houston, TX (43). Phylogenetic analysis of the VP1 amino acid sequence (GenBank accession number AEQ77282.1) confirmed that it belonged to the GI.7 genotype and showed that it is distant from the structurally characterized GI.1 and GI.2 strains (data not shown).…”

Section: Resultsmentioning

confidence: 82%

Structural Analysis of Determinants of Histo-Blood Group Antigen Binding Specificity in Genogroup I Noroviruses

Shanker

Czakó

Sankaran

et al. 2014

J Virol

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Human noroviruses (NoVs) cause acute epidemic gastroenteritis. Susceptibility to the majority of NoV infections is determined by genetically controlled secretor-dependent expression of histo-blood group antigens (HBGAs), which are also critical for NoV attachment to host cells. Human NoVs are classified into two major genogroups (genogroup I [GI] and GII), with each genogroup further divided into several genotypes. GII NoVs are more prevalent and exhibit periodic emergence of new variants, suggested to be driven by altered HBGA binding specificities and antigenic drift. Recent epidemiological studies show increased activity among GI NoVs, with some members showing the ability to bind nonsecretor HBGAs. NoVs bind HBGAs through the protruding (P) domain of the major capsid protein VP1. GI NoVs, similar to GII, exhibit significant sequence variations in the P domain; it is unclear how these variations affect HBGA binding specificities. To understand the determinants of possible strainspecific HBGA binding among GI NoVs, we determined the structure of the P domain of a GI.7 clinical isolate and compared it to the previously determined P domain structures of GI.1 and GI.2 strains. Our crystallographic studies revealed significant structural differences, particularly in the loop regions of the GI.7 P domain, altering its surface topography and electrostatic landscape and potentially indicating antigenic variation. The GI.7 strain bound to H-and A-type, Lewis secretor, and Lewis nonsecretor families of HBGAs, allowing us to further elucidate the structural determinants of nonsecretor HBGA binding among GI NoVs and to infer several contrasting and generalizable features of HBGA binding in the GI NoVs. IMPORTANCEHuman noroviruses (NoVs) cause acute epidemic gastroenteritis. Recent epidemiological studies have shown increased prevalence of genogroup I (GI) NoVs. Although secretor-positive status is strongly correlated with NoV infection, cases of NoV infection associated with secretor-negative individuals are reported. Biochemical studies have shown that GI NoVs exhibit genotypedependent binding to nonsecretor histo-blood group antigens (HBGAs). From our crystallographic studies of a GI.7 NoV, in comparison with previous studies on GI.1 and GI.2 NoVs, we show that genotypic differences translate to extensive structural changes in the loop regions that significantly alter the surface topography and electrostatic landscape of the P domain; these features may be indicative of antigenic variations contributing to serotypic differentiation in GI NoVs and also differential modulation of the HBGA binding characteristics. A significant finding is that the threshold length and the structure of one of the loops are critical determinants in the binding of GI NoVs to nonsecretor HBGAs.

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“…In the United States alone, they annually cause 19-21 million symptomatic infections resulting in up to 71,000 hospitalizations and 800 deaths. 1 In fact, they have become the leading cause of severe childhood diarrhea since the introduction of a successful rotavirus vaccination program 2,3 and they are the predominant cause of foodborne disease outbreaks. 4 In developing countries, HuNoVs are likely even more devastating, an idea underscored by an estimate that they cause over a million clinic visits and 200,000 fatalities in young children in impoverished parts of the globe.…”

Section: Introductionmentioning

confidence: 99%

Identification of a novel cellular target and a co-factor for norovirus infection – B cells & commensal bacteria

Karst

2015

Gut Microbes

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Noroviruses: The Most Common Pediatric Viral Enteric Pathogen at a Large University Hospital After Introduction of Rotavirus Vaccination

Cited by 156 publications

References 9 publications

Absence of Genetic Differences among G10P[11] Rotaviruses Associated with Asymptomatic and Symptomatic Neonatal Infections in Vellore, India

Absence of Genetic Differences among G10P[11] Rotaviruses Associated with Asymptomatic and Symptomatic Neonatal Infections in Vellore, India

Structural Analysis of Determinants of Histo-Blood Group Antigen Binding Specificity in Genogroup I Noroviruses

Identification of a novel cellular target and a co-factor for norovirus infection – B cells & commensal bacteria

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