Prolonged Norovirus Shedding in Infants ≤6 Months of Age With Gastroenteritis

Murata, Toshiro; Katsushima, Noriko; Mizuta, Katsumi; Muraki, Yasushi; Hongō, Seiji; Matsuzaki, Yoko

doi:10.1097/01.inf.0000247102.04997.e0

Cited by 144 publications

(107 citation statements)

References 18 publications

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“…While typically an acute disease, norovirus infections can be serious in the young, old, and immunocompromised, as these groups are at risk for more severe disease and death (1)(2)(3). Norovirus is spread rapidly in environments where people are found in close proximity, including schools and daycare centers, nursing homes, cruise ships, and hospitals.…”

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confidence: 99%

Within-Host Evolution Results in Antigenically Distinct GII.4 Noroviruses

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Lindesmith

Ferris

et al. 2014

J Virol

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Genogroup II, genotype 4 (GII.4) noroviruses are known to rapidly evolve, with the emergence of a new primary strain every 2 to 4 years as herd immunity to the previously circulating strain is overcome. Because viral genetic diversity is higher in chronic than in acute infection, chronically infected immunocompromised people have been hypothesized to be a potential source for new epidemic GII.4 strains. However, while some capsid protein residues are under positive selection and undergo patterned changes in sequence variation over time, the relationships between genetic variation and antigenic variation remains unknown. Based on previously published GII.4 strains from a chronically infected individual, we synthetically reconstructed virus-like particles (VLPs) representing early and late isolates from a small-bowel transplant patient chronically infected with norovirus, as well as the parental GII.4-2006b strain. We demonstrate that intrahost GII.4 evolution results in the emergence of antigenically distinct strains over time, comparable to the variation noted between the chronologically predominant GII.4 strains GII.4-2006b and GII.4-2009. Our data suggest that in some individuals the evolution that occurs during a chronic norovirus infection overlaps with changing antigenic epitopes that are associated with successive outbreak strains and may select for isolates that are potentially able to escape herd immunity from earlier isolates. IMPORTANCENoroviruses are agents of gastrointestinal illness, infecting an estimated 21 million people per year in the United States alone. In healthy individuals, symptomatic infection typically resolves within 24 to 48 h. However, symptoms may persist for years in immunocompromised individuals, and development of successful treatments for these patients is a continuing challenge. This work is relevant to the design of successful norovirus therapeutics for chronically infected patients; provides support for previous assertions that chronically infected individuals may serve as reservoirs for new, antigenically unique emergent strains; and furthers our understanding of genogroup II, genotype 4 (GII.4) norovirus immune-driven molecular evolution.

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confidence: 99%

Within-Host Evolution Results in Antigenically Distinct GII.4 Noroviruses

Debbink

Lindesmith

Ferris

et al. 2014

J Virol

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“…ORF1 encodes a nonstructural polyprotein that is processed posttranslationally by the viral protease; ORF2 encodes the capsid protein, the major structural component, which also mediates viral entry into target cells; ORF3 encodes a small basic protein that is associated with virions and is required for capsid assembly (12); and ORF4, which is highly conserved, was recently shown to play a role in murine norovirus pathogenesis (13). Despite the relatively brief duration of symptomatic NV illness, it is becoming increasingly clear that viral shedding can continue for weeks to months in immunocompetent individuals (14)(15)(16)(17)(18) and even for years in immunosuppressed patients (19)(20)(21)(22). The immunologic and virologic basis for NV persistence, however, remains unknown.…”

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confidence: 99%

Persistent Enteric Murine Norovirus Infection Is Associated with Functionally Suboptimal Virus-Specific CD8 T Cell Responses

Tomov

Osborne

Dolfi

et al. 2013

J Virol

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“…64,65 Long-term shedding was described among children less than 6 months, 63 in elderly, 64 hospitalized and immunosuppressed patients. 62 Predictive modeling of viral shedding classifies shedding into regular shedding with a mean of 14-16 d and long shedding with a mean ranging between 105 and 136 d 66 Recent studies suggest the lack of a significant difference of virus shedding between asymptomatic and symptomatic NoV infections despite the individual variation in virus peak levels detected in stool.…”

Section: Viral Shedding Natural Infection With Nov and Seroprotectionmentioning

confidence: 99%

“…59,60 More than 90% of individuals are seropositive to NoV by the time they reach adulthood; however, the role of pre-existing immunity is still not fully understood when related to protection or reducing the risk of acquiring new NoV infections. 15 The fact that asymptomatic infection occurs at an early age as reported by outbreak and human challenge studies 48,[61][62][63] provides critical insight to the potential reservoir of transmission at an early age and its clear implication on the need for an effective vaccine.…”

Section: Viral Shedding Natural Infection With Nov and Seroprotectionmentioning

confidence: 99%

Norovirus vaccines: Correlates of protection, challenges and limitations

Melhem

2016

Human Vaccines & Immunotherapeutics

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Norovirus (NoV) is responsible for at least 50% of all gastroenteritis outbreaks worldwide. NoVs are classified into 6 different genogroups (GGI-GGVI) based on the viral capsid protein with NoV genogroup II genotype 4 (GII.4) being the predominant strain causing human diseases. Supportive therapy involving reversal of dehydration and electrolyte deficiency is the main treatment of NoV gastroenteritis. However, the worldwide increased recognition of NoV as an important agent of diarrheal gastroenteritis prompted researchers to focus on establishing preventive strategies conferring long-lasting immunity. This review describes the current status of animal and human vaccine models/studies targeting NoV and addresses the factors hampering the development of a broadly effective vaccine.

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Prolonged Norovirus Shedding in Infants ≤6 Months of Age With Gastroenteritis

Abstract: Long-term virus shedding after the disappearance of clinical symptoms was observed. Caution should be exercised when handling the excrement of infants and young children infected with NV.

Cited by 144 publications

References 18 publications

Within-Host Evolution Results in Antigenically Distinct GII.4 Noroviruses

Within-Host Evolution Results in Antigenically Distinct GII.4 Noroviruses

Persistent Enteric Murine Norovirus Infection Is Associated with Functionally Suboptimal Virus-Specific CD8 T Cell Responses

Norovirus vaccines: Correlates of protection, challenges and limitations

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