In:
PLOS Pathogens, Public Library of Science (PLoS), Vol. 17, No. 5 ( 2021-5-6), p. e1009527-
Abstract:
Baloxavir is approved in several countries for the treatment of uncomplicated influenza in otherwise-healthy and high-risk patients. Treatment-emergent viruses with reduced susceptibility to baloxavir have been detected in clinical trials, but the likelihood of widespread occurrence depends on replication capacity and onward transmission. We evaluated the fitness of A/H3N2 and A/H1N1pdm09 viruses with the polymerase acidic (PA) I38T-variant conferring reduced susceptibility to baloxavir relative to wild-type (WT) viruses, using a competitive mixture ferret model, recombinant viruses and patient-derived virus isolates. The A/H3N2 PA/I38T virus showed a reduction in within-host fitness but comparable between-host fitness to the WT virus, while the A/H1N1pdm09 PA/I38T virus had broadly similar within-host fitness but substantially lower between-host fitness. Although PA/I38T viruses replicate and transmit between ferrets, our data suggest that viruses with this amino acid substitution have lower fitness relative to WT and this relative fitness cost was greater in A/H1N1pdm09 viruses than in A/H3N2 viruses.
Type of Medium:
Online Resource
ISSN:
1553-7374
DOI:
10.1371/journal.ppat.1009527
DOI:
10.1371/journal.ppat.1009527.g001
DOI:
10.1371/journal.ppat.1009527.g002
DOI:
10.1371/journal.ppat.1009527.g003
DOI:
10.1371/journal.ppat.1009527.g004
DOI:
10.1371/journal.ppat.1009527.g005
DOI:
10.1371/journal.ppat.1009527.g006
DOI:
10.1371/journal.ppat.1009527.g007
DOI:
10.1371/journal.ppat.1009527.s001
DOI:
10.1371/journal.ppat.1009527.s002
DOI:
10.1371/journal.ppat.1009527.s003
DOI:
10.1371/journal.ppat.1009527.s004
DOI:
10.1371/journal.ppat.1009527.s005
DOI:
10.1371/journal.ppat.1009527.s006
DOI:
10.1371/journal.ppat.1009527.s007
DOI:
10.1371/journal.ppat.1009527.s008
DOI:
10.1371/journal.ppat.1009527.s009
DOI:
10.1371/journal.ppat.1009527.s010
DOI:
10.1371/journal.ppat.1009527.s011
DOI:
10.1371/journal.ppat.1009527.s012
DOI:
10.1371/journal.ppat.1009527.s013
DOI:
10.1371/journal.ppat.1009527.r001
DOI:
10.1371/journal.ppat.1009527.r002
DOI:
10.1371/journal.ppat.1009527.r003
DOI:
10.1371/journal.ppat.1009527.r004
Language:
English
Publisher:
Public Library of Science (PLoS)
Publication Date:
2021
detail.hit.zdb_id:
2205412-1
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