Single Base Substitutions in the Capsid Region of the Norovirus Genome during Viral Shedding in Cases of Infection in Areas Where Norovirus Infection Is Endemic

Obara, Mayumi; Hasegawa, Sumiyo; Iwai, Masae; Horimoto, Eiji; Nakamura, Kenzo; Kurata, Takeshi; Saito, N.; Oe, Hiroshi; Takizawa, Takenori

doi:10.1128/jcm.01932-07

Cited by 13 publications

(10 citation statements)

References 28 publications

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“…Noroviruses typically cause acute infection in healthy individuals, resulting in symptomatic infection for 24 to 48 h, followed by virus shedding for 2 to 4 weeks (18,19). However, some immu-nocompromised individuals, such as transplant patients on immunosuppressive drugs, those with primary immunodeficiencies, cancer patients undergoing chemotherapy, and those with HIV infections, may develop chronic norovirus infection.…”

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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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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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“…As described by Obara et al, two hotel employees shed NoV for one and two months, respectively, and the mutations were observed at nine nucleotide positons in VP1 including epitope A(297). They also noted that these changes seemed not to be caused by immune‐driven pressure because the mutations were not restricted to the P2 domain [Obara et al, ]. However in this study, the mutations in the epitopes A (297), D (394), and E (407) in inpatient six, and epitopes A (294, 297, 368, and 372) and D (393 and 394) in inpatient 8 were observed.…”

Section: Discussionmentioning

confidence: 46%

Long‐term viral shedding and viral genome mutation in norovirus infection

Miyoshi

Uchino

Yoshida

et al. 2015

Journal of Medical Virology

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The duration of viral shedding in the patients from two outbreaks and four sporadic cases of norovirus (NoV) infections was investigated. The longest period of viral shedding into feces was for 173 days in an inpatient from one case of outbreak. The VP1 sequence from two long-term viral shedding cases in the outbreak revealed four synonymous and one non-synonymous mutations in one inpatient at 26 days from the onset of illness, and nine synonymous and two non-synonymous mutations and a deletion, 10 synonymous mutations and a deletion in other inpatient at 29 days and 54 days from the onset of illness, respectively. Ten of the 11 amino acid positions detected in these two inpatients were in the outermost P2 domain of the viral capsid protein, and mutations at positions 295, 297, and 394 were shared in the inpatients. Mutations in the P2 domain were in epitopes A and D or near epitopes A, C, and E, suggesting that the long-term carrier state of norovirus infection contributes to the generation of escape mutants by host immunoselection.

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“…Molecular analysis of the sequences these amplicons were also compared with those from the prototype strains from each of the NoV genogroups (GI-GVI), and in all twelve cases single base substitutions from either C to T, or T to C, were observed between our amplicons and rat NoV references. While these base changes were not predicted to lead to amino acid substitutions, these polymorphisms probably describe the independent evolution of NoV strains [30]. The recombination of single-stranded RNA viruses, allowing the emergence of new viral strains, is known to occur often in the Caliciviridae family [29].…”

Section: Discussionmentioning

confidence: 99%

A semi-nested RT-PCR assay for detection of norovirus in rat fecal samples

et al. 2019

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Norovirus is a highly prevalent pathogen that can infect a wide range of host species. Thus far, there have only been two reports of norovirus infection in rats. Diagnostic assays for the detection of norovirus are well established, but a specific molecular assay for the diagnosis of norovirus infection in laboratory rats has not yet been reported. In this study, we describe the development of a sensitive, semi-nested RT-PCR assay for detection of norovirus in fecal samples from Rattus norvegicus, reared in animal facilities under different sanitary barrier conditions. Additionally, we describe the first report of the presence of norovirus in rat colonies from Brazilian animal facilities.

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Single Base Substitutions in the Capsid Region of the Norovirus Genome during Viral Shedding in Cases of Infection in Areas Where Norovirus Infection Is Endemic

Cited by 13 publications

References 28 publications

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

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

Long‐term viral shedding and viral genome mutation in norovirus infection

A semi-nested RT-PCR assay for detection of norovirus in rat fecal samples

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