Intrahost norovirus evolution in chronic infection over 5 years of shedding in a kidney transplant recipient

Steyer, Andrej (author), Konte, Tilen (author), Sagadin, Martin (author), Kolenc, Marko (author), Škoberne, Andrej (author), Germ, Julija (author), Dovč, Tadeja (author), Arnol, Miha (author), Poljšak-Prijatelj, Mateja (author)

Noroviruses are the leading cause of acute gastroenteritis, and they can affect humans of all age groups. In immunocompromised patients, norovirus infections can develop into chronic diarrhea or show prolonged asymptomatic virus shedding. Chronic norovirus infections are frequently reported for solid organ transplant recipients, with rapid intrahost norovirus evolution seen. In this report, we describe a case of chronic norovirus infection in an immunocompromised patient who was followed up for over 5 years. The purpose of the study was to specify the norovirus evolution in a chronically infected immunocompromised host and identify possible selection sites in norovirus capsid protein. During the follow-up period, 25 sequential stool samples were collected and nine of them were selected to generate amplicons covering viral RNA-dependent RNA polymerase (RdRp) and viral capsid protein (VP1) genes. Amplicons were sequenced using next-generation sequencing. Single nucleotide polymorphisms were defined, which demonstrated a nearly 3-fold greater mutation rate in the VP1 genome region compared to the RdRp genome region (7.9 vs. 2.8 variable sites/100 nucleotides, respectively). This indicates that mutations in the virus genome were not accumulated randomly, but are rather the result of mutant selection during the infection cycle. Using ShoRAH software we were able to reconstruct haplotypes occurring in each of the nine selected samples. The deduced amino-acid haplotype sequences were aligned and the positions were analyzed for selective pressure using the Datamonkey program. Only 12 out of 25 positive selection sites were within the commonly described epitopes A, B, C, and D of the VP1 protein. New positive selection sites were determined that have not been described before and might reflect adaptation of the norovirus toward optimal histo-blood-group antigen binding, or modification of the norovirus antigenic properties. These data provide new insights into norovirus evolutionary dynamics and indicate new putative epitope "hot-spots" of modified and optimized norovirus-host interactions.

• Language: English
• Keywords: norovirus, molecular evolution, chronic infection, solid organ transplantation, HBGA binding
• Work type: Article
• Typology: 1.01 - Original Scientific Article
• Organization: MF - Faculty of Medicine
• Publication status: Published
• Publication version: Version of Record
• Year: 2018
• Number of pages: 12 str.
• Numbering: Vol. 9, art. 371
• PID: 20.500.12556/RUL-128737
• UDC: 578
• ISSN on article: 1664-302X
• DOI: 10.3389/fmicb.2018.00371
• COBISS.SI-ID: 33668057
• Publication date in RUL: 26.07.2021

Record is a part of a journal

• Title: Frontiers in microbiology
• Shortened title: Front. microbiol.
• Publisher: Frontiers Research Foundation
• ISSN: 1664-302X
• COBISS.SI-ID: 4146296

Licences

• License: CC BY 4.0, Creative Commons Attribution 4.0 International
• Link: http://creativecommons.org/licenses/by/4.0/
• Description: This is the standard Creative Commons license that gives others maximum freedom to do what they want with the work as long as they credit the author.
• Licensing start date: 02.03.2018

Secondary language

• Language: Slovenian
• Keywords: norovirus, molekularna evolucija, kronična okužba, presaditev organov, vezava HBGA

Projects

• Funder: ARRS - Slovenian Research Agency
• Project number: P3-0083
• Name: Odnosi parazitskega obstajanja