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Intrahost viral evolution during chronic sapovirus infections.

BACKGROUND: Sapovirus is a common cause of self-limiting diarrhea. In immunocompromised individuals chronic infections occur, but are incompletely investigated.

OBJECTIVES: To investigate viral evolution in immunocompromised hosts during chronic sapovirus infection.

STUDY DESIGN: From January 2010 to September 2018 stool samples of 5333 in-patients were analyzed for the presence of sapovirus RNA by real-time RT-PCR. In follow-up samples of chronic diarrhea cases nucleic acid sequencing of sapovirus genomes was performed. Amino acid mutations were identified by alignments and compared to data from GenBank. Sapovirus genotypes were assessed by phylogenetic analysis of viral capsid gene (VP1).

RESULTS: Sapovirus RNA was present in 146 stool samples of 95 patients (1.8%), most frequently in young children and infants. In patients older than 14 years, sapoviruses were exclusively detected in immunocompromised patients. Chronic diarrhea occurred in almost one third of the sapovirus positive immunocompromised individuals (n = 5) and was established by different sapovirus genotypes (GI.2, GII.1, GII.3). The maximum observed duration of sapovirus shedding was 119 days. Accumulation of amino acid mutations during chronic infection was most often detected within VP1 P2 protruding subdomain. Reduction of immunosuppression was associated with decrease of viral load and clearance of sapovirus in stool.

CONCLUSIONS: Clinicians should consider immunocompromised individuals at risk to develop chronic diarrhea due to persistence of SaV infection. The identified VP1 mutations contribute to an understanding of sapovirus-host interactions. For further conclusions regarding virus immune escape and altered viral fitness structural data on sapovirus capsid and virus/receptor complex are necessary.

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