Journal article
Norovirus Polymerase Fidelity Contributes to Viral Transmission In Vivo
Intrahost genetic diversity and replication error rates are intricately linked to RNA virus pathogenesis, with alterations in viral polymerase fidelity typically leading to attenuation during infections in vivo. We have previously shown that norovirus intrahost genetic diversity also influences viral pathogenesis using the murine norovirus model, as increasing viral mutation frequency using a mutagenic nucleoside resulted in clearance of a persistent infection in mice.
Given the role of replication fidelity and genetic diversity in pathogenesis, we have now investigated whether polymerase fidelity can also impact virus transmission between susceptible hosts. We have identified a high-fidelity norovirus RNA-dependent RNA polymerase mutant (I391L) which displays delayed replication kinetics in vivo but not in cell culture.
The I391L polymerase mutant also exhibited lower transmission rates between susceptible hosts than the wild-type virus and, most notably, another replication defective mutant that has wild-type levels of polymerase fidelity. These results provide the first experimental evidence that norovirus polymerase fidelity contributes to virus transmission between hosts and that maintaining diversity is important for the establishment of infection.
This work supports the hypothesis that the reduced polymerase fidelity of the pandemic GII.4 human norovirus isolates may contribute to their global dominance.
Language: | English |
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Publisher: | American Society for Microbiology |
Year: | 2016 |
Pages: | e00279-16-e00279-16 |
ISSN: | 23795042 , 15359786 and 15359778 |
Types: | Journal article |
DOI: | 10.1128/mSphere.00279-16 |
ORCIDs: | Arias Esteban, Armando , 0000-0002-5640-2266 and 0000-0002-9483-510X |
Microbiology QR1-502 noroviruses polymerase fidelity quasispecies virus transmission