Infectivity of Norovirus GI and GII from Bottled Mineral Water during a Waterborne Outbreak, Spain

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Norovirus infections are a leading cause of acute gastroenteritis outbreaks worldwide and across all age groups, with two main genogroups (GI and GII) infecting humans. The aim of our study was to investigate the occurrence of norovirus in saliva samples from individuals involved in outbreaks of acute gastroenteritis in closed and semiclosed institutions, and its relationship with the virus strain, virus shedding in stool, the occurrence of symptoms, age, and the secretor status of the individual. Epidemiological and clinical information was gathered from norovirus outbreaks occurring in Catalonia, Spain during 2017–2018, and stool and saliva samples were collected from affected and exposed resident individuals and workers. A total of 347 saliva specimens from 25 outbreaks were analyzed. Further, 84% of individuals also provided a paired stool sample. For GII infections, norovirus was detected in 17.9% of saliva samples from symptomatic cases and 5.2% of asymptomatic individuals. Positivity in saliva occurred in both secretors and nonsecretors. None of the individuals infected by norovirus GI was positive for the virus in saliva. Saliva positivity did not correlate with any of the studied symptoms but did correlate with age ≥ 65 years old. Individuals who were positive in saliva showed higher levels of virus shedding in stool. Mean viral load in positive saliva was 3.16 ± 1.08 log10 genome copies/mL, and the predominance of encapsidated genomes was confirmed by propidium monoazide (PMA)xx-viability RTqPCR assay. The detection of norovirus in saliva raises the possibility of oral-to-oral norovirus transmission during the symptomatic phase and, although to a lesser extent, even in cases of asymptomatic infections.

Section: Discussionsupporting

confidence: 75%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Detection of Norovirus in Saliva Samples from Acute Gastroenteritis Cases and Asymptomatic Subjects: Association with Age and Higher Shedding in Stool

Anfruns-Estrada

Sabrià

Fuentes

et al. 2020

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“…However, it should be read with caution that viral RNA level does not equal the amount of infectious virus. In a very recent study, by using viability PCR, it was revealed that only around 5% of all norovirus RNA genomes detected by qPCR came from intact virions [ 51 ]. Interestingly, one study revealed that HuNoV particles were packed within exosome-derived small vesicles of less than 200 nm [ 52 ].…”

Section: Discussionmentioning

confidence: 99%

Targeted Profiling of Immunological Genes during Norovirus Replication in Human Intestinal Enteroids

Chan

Zhang

Wong

et al. 2021

Norovirus is the leading cause of acute gastroenteritis worldwide. The pathogenesis of norovirus and the induced immune response remain poorly understood due to the lack of a robust virus culture system. The monolayers of two secretor-positive Chinese human intestinal enteroid (HIE) lines were challenged with two norovirus pandemic GII.4 Sydney strains. Norovirus RNA replication in supernatants and cell lysates were quantified by RT-qPCR. RNA expression levels of immune-related genes were profiled using PCR arrays. The secreted protein levels of shortlisted upregulated genes were measured in supernatants using analyte-specific enzyme-linked immunosorbent assay (ELISA). Productive norovirus replications were achieved in three (75%) out of four inoculations. The two most upregulated immune-related genes were CXCL10 (93-folds) and IFI44L (580-folds). Gene expressions of CXCL10 and IFI44L were positively correlated with the level of norovirus RNA replication (CXCL10: Spearman’s r = 0.779, p < 0.05; IFI44L: r = 0.881, p < 0.01). The higher level of secreted CXCL10 and IFI44L proteins confirmed their elevated gene expression. The two genes have been reported to be upregulated in norovirus volunteer challenges and natural human infections by other viruses. Our data suggested that HIE could mimic the innate immune response elicited in natural norovirus infection and, therefore, could serve as an experimental model for future virus-host interaction and antiviral studies.

“…GII strains account for ~90% of infections and occur earlier in life than GI infections [122,123]. Infection follows a fecal-oral route, with infection possible with small amounts of virion exposure [124][125][126][127]. Once infected, children may shed virus for weeks post-infection [128].…”

Section: Virus Backgroundmentioning

confidence: 99%

Serological Humoral Immunity Following Natural Infection of Children with High Burden Gastrointestinal Viruses

Zweigart

Becker‐Dreps

Bucardo

et al. 2021

Acute gastroenteritis (AGE) is a major cause of morbidity and mortality worldwide, resulting in an estimated 440,571 deaths of children under age 5 annually. Rotavirus, norovirus, and sapovirus are leading causes of childhood AGE. A successful rotavirus vaccine has reduced rotavirus hospitalizations by more than 50%. Using rotavirus as a guide, elucidating the determinants, breath, and duration of serological antibody immunity to AGE viruses, as well as host genetic factors that define susceptibility is essential for informing development of future vaccines and improving current vaccine candidates. Here, we summarize the current knowledge of disease burden and serological antibody immunity following natural infection to inform further vaccine development for these three high-burden viruses.