Prevalence of Reovirus‐Specific Antibodies in Young Children in Nashville, Tennessee

Tai, J Y; Williams, John V.; Edwards, Kathryn M.; Wright, Peter F.; Crowe, James E.; Dermody, Terence S.

doi:10.1086/428911

Cited by 115 publications

(85 citation statements)

References 11 publications

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“…3 When administering viruses as therapeutic agents, it is possible that the route of vector delivery may qualitatively and quantitatively influence the nature of the antiviral immune response. For example, intracranial and intralesional delivery (sites of relative immune privilege) may result in a different response to systemic intravenous administration.…”

Section: Introductionmentioning

confidence: 99%

Characterization of the adaptive and innate immune response to intravenous oncolytic reovirus (Dearing type 3) during a phase I clinical trial

et al. 2008

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Section: Introductionmentioning

confidence: 99%

Characterization of the adaptive and innate immune response to intravenous oncolytic reovirus (Dearing type 3) during a phase I clinical trial

et al. 2008

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“…They are ubiquitous nonpathogenic viruses that can be isolated from the respiratory and gastrointestinal tracts of humans (1), although they are not associated with a specific clinical syndrome. Most healthy adults possess antireoviral antibodies, suggesting a high incidence of subclinical infection in early life (2). Three serotypes of reovirus (type 1 Lang, type 2 Jones, and type 3 Abney and type 3 Dearing) have been defined based on their antibody neutralization and hemagglutinationinhibitory activities (3).…”

mentioning

confidence: 99%

Enhanced In vitro and In vivo Cytotoxicity of Combined Reovirus and Radiotherapy

Twigger

Vidal

White

et al. 2008

Clinical Cancer Research

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Purpose:To test combination treatment schedules of reovirus and radiation in human and murine tumor cells in vitro and in vivo. Experimental Design: In vitro cytotoxicity and cell cycle effects of reovirus given alone and combined with radiotherapy were assessed by colorimetric, tissue culture infectious dose 50, and fluorescence-activated cell sorting^based assays. Interactions between the agents were evaluated using combination index analysis. The effect of different schedules of reovirus and radiotherapy on viral replication and cytotoxicity was tested in vitro and the combination was assessed in three tumor models in vivo. Results: Characterization of reovirus cytotoxicity in a panel of cell lines yielded a range of sensitivities. Combined reovirus and radiotherapy yielded statistically significantly increased cytotoxicity, particularly in cell lines with moderate susceptibility to reovirus alone. The enhanced cytotoxicity of the combination occurred independently of treatment sequence or schedule. Radiation did not affect viral replication and only reduced reoviral cytotoxicity after clinically irrelevant single doses (>50 Gy). Combination index analysis revealed synergy between radiation (3-10 Gy) and reovirus at multiplicities of infection between 0.001and 1. Combination treatment significantly increased apoptosis in tumor cells relative to either single-agent treatment. In vivo studies using xenograft and syngeneic tumors showed enhanced activity of the combination relative to reovirus or radiation alone (P < 0.001).Conclusions: Combining reovirus and radiotherapy synergistically enhances cytotoxicity in a variety of tumor cells in vitro and in vivo.These results offer strong support for translational clinical trials of reovirus plus radiotherapy that have been initiated in the clinic.

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“…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). Similarly, our NGS data indicated that the Vellore neonates were not infected with orthoreovirus, reovirus, or saffold virus, all RNA viruses that frequently infect children (67,70,76,(80)(81)(82)(83). At its simplest, the absence of NGS reads for these RNA viruses suggests a possible lack of neonatal exposure or susceptibility to these viruses or a lack of circulation of such viruses in the Vellore area or CMC nurseries.…”

Section: Discussionmentioning

confidence: 48%

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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Prevalence of Reovirus‐Specific Antibodies in Young Children in Nashville, Tennessee

Cited by 115 publications

References 11 publications

Characterization of the adaptive and innate immune response to intravenous oncolytic reovirus (Dearing type 3) during a phase I clinical trial

Characterization of the adaptive and innate immune response to intravenous oncolytic reovirus (Dearing type 3) during a phase I clinical trial

Enhanced In vitro and In vivo Cytotoxicity of Combined Reovirus and Radiotherapy

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

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