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Human Norovirus Evolution in a Chronically Infected Host.

Sylvie Y Doerflinger1, Stefan Weichert2, Anna Koromyslova1

  • 1Department of Infectious Diseases, Virology, University of Heidelberg, Heidelberg, Germany; Schaller Research Group at the University of Heidelberg and the DKFZ, Heidelberg, Germany.

Msphere
|April 14, 2017
PubMed
Summary

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This summary is machine-generated.

Chronic norovirus infections in an immunocompromised patient yielded two new GII.4 variants. These variants showed distinct antigenicity but similar histo-blood group antigen binding, suggesting chronic infections may not generate epidemic strains.

Area of Science:

  • Virology
  • Immunology
  • Gastroenterology

Background:

  • Human noroviruses cause acute gastroenteritis and can be shed long after symptom resolution, potentially leading to transmission.
  • Chronic norovirus infections lasting months or years are hypothesized to act as reservoirs for novel strain generation, potentially evading herd immunity.
  • Norovirus genogroup II genotype 4 (GII.4) variants have dominated globally, with their emergence and persistence mechanisms still under investigation.

Purpose of the Study:

  • To investigate noroviruses isolated from a patient with a chronic infection exceeding six years.
  • To analyze the genetic, antigenic, and binding characteristics of norovirus capsid quasi-species during long-term infection.
  • To determine if chronically infected individuals can generate novel norovirus variants capable of causing outbreaks.
Keywords:
chronic infectionevolutionnorovirus

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Main Methods:

  • Analysis of norovirus capsid sequences isolated from a patient with a chronic infection.
  • Clustering of quasi-sequences into genetic and antigenic types.
  • Assessment of histo-blood group antigen (HBGA) and human milk oligosaccharide (HMO) binding profiles.
  • Comparison of isolated sequences with existing databases for novelty.

Main Results:

  • Isolated norovirus capsid sequences clustered into two main genetic types (A and B) with distinct antigenicities.
  • Numerous amino acid substitutions on the capsid surface did not alter HBGA binding profiles.
  • Divergent binding profiles were observed with human milk oligosaccharides (HMOs) between types A and B.
  • The isolated sequences, representing two new GII.4 variants, showed approximately 90% amino acid identity to known sequences and were not found in databases.
  • Despite quasi-species, HBGA binding remained similar between the two identified antigenic clusters.

Conclusions:

  • Chronically infected patients may not necessarily generate novel noroviruses that lead to widespread outbreaks.
  • The limited sequence divergence and conserved HBGA binding suggest restricted transmission potential for these chronic GII.4 variants.
  • Further research is needed to understand the full implications of chronic norovirus infections on viral evolution and epidemiology.