What is the reservoir of emergent human norovirus strains?

Abstract

Since 1996, there have been at least six human norovirus pandemics. All of the pandemic strains are genetically related, segregating in the genogroup II, genotype 4 (GII.4) cluster within the Norovirus genus. Evidence indicates that these strains are closely related but antigenically distinct, supporting immune-driven viral evolution. Thus, norovirus vaccines will likely require periodic reformulation to protect from newly emergent strains. A major obstacle is that the reservoir of emergent strains is unknown. Noroviruses display tight species specificity and there is no evidence supporting zoonotic transmission, so an animal reservoir is considered unlikely. Moreover, available data indicate minimal viral diversity in most natural human infections. In this Gem, we discuss the widely speculated idea that chronically infected immunocompromised individuals are norovirus reservoirs and provide a rationale for the theory that elderly and malnourished hosts may also represent norovirus reservoirs.

FIG 1

Model of RNA virus evolution. The current framework for the adaptation rate of fast-evolving RNA viruses like noroviruses (black line) is the net result of the complexity of the viral quasispecies resulting from the inherent error rate of the RdRp (red line), the strength of the selective pressures applied to this viral population by the host (blue line), and the replication rate of the virus (not accounted for in this model). In this model, immunocompromised hosts (point 1) have a complex quasispecies because of the high error rate of the RdRp but low adaptation because of reduced selective pressure, healthy hosts (point 3) develop a robust immune response that limits the development of a complex quasispecies, and hosts with intermediate immunity (point 2) display the highest adaptation rate because of the development of weak selective pressure—this pressure is insufficient to completely control viral replication, so a complex quasispecies develops, but it is sufficient to drive the evolution of the virus. Adapted from reference .