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

Abstract

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.

Viral shedding in gastroenteritis in children caused by variants and novel recombinant norovirus infections

“…NoV infection can induce an immune response and inflammation and may drive viral replication, prolonging shedding during acute infection. [20] The GII.4 strain had a longer shedding duration than the other NoV strains we studied. A longer shedding period could be associated with gene mutations or recombination.…”

“…A longer shedding period could be associated with gene mutations or recombination. [ 20 , 21 ] Hospitalized patients infected with NoV strains with mutations in the VP1 domain were observed to shed the virus for up to 2 months. [22] Mutations in P2 of the VP1 domain are also associated with prolonged shedding.…”

A next generation sequencing-based method to study the intra-host genetic diversity of norovirus in patients with acute and chronic infection

“…We observed an enrichment of non-synonymous SNVs in the P2 domain of VP1 which matches the expectation that the most exposed and possibly the most antigenic part of the virus bears the highest pressure to diverge. In fact, the majority of studies analyzing NoV intra-host genetic diversity have been restricted to identify potential changes at VP1 [ 12 , 14 , 21 , 24 , 35 , 36 ]. By analyzing near-full length NoV genomes, we also observed an enrichment of non-synonymous mutations in VP2, which suggests that during chronic infection this gene can also be under pressure to diverge.…”

“…The gold standard method to study intra-host NoV populations involves cloning viral RT-PCR amplicons into plasmids followed by Sanger sequencing [ 16 , 19 , 20 , 24 ], a labour intensive method that requires a relatively large number of clones to be processed in order to obtain an accurate assessment of the viral diversity. An alternative approach uses next generation sequencing (NGS) technologies, which process millions of fragments of nucleic acid in a single experiment.…”

Bioactive Ingredients in Chinese Herbal Medicines That Target Non-coding RNAs: Promising New Choices for Disease Treatment

“…Antibiotics and antiviral drugs are basic treatments for infectious diseases; however, a deteriorating situation caused by antibiotic abuse, drug-resistance, and viral mutations is shifting the focus of research attention to other therapeutic and complementary drugs for treatment of these conditions (Miyoshi et al, 2015; Jiang et al, 2019). To date, two bioactive ingredients of CHMs have been found to contribute to the treatment of infection through regulation of miRNAs.…”