tetano
Editor, Senior Moderator
J Infect Dis. 2019 Sep 21. pii: jiz472. doi: 10.1093/infdis/jiz472. [Epub ahead of print]
[h=1]Replicative fitness of seasonal influenza A viruses with decreased susceptibility to baloxavir.[/h] Chesnokov A[SUP]1[/SUP], Patel MC[SUP]1,[/SUP][SUP]2[/SUP], Mishin VP[SUP]1[/SUP], De La Cruz JA[SUP]1,[/SUP][SUP]2[/SUP], Lollis L[SUP]1,[/SUP][SUP]2[/SUP], Nguyen HT[SUP]1,[/SUP][SUP]2[/SUP], Dugan V[SUP]1[/SUP], Wentworth DE[SUP]1[/SUP], Gubareva LV[SUP]1[/SUP].
[h=3]Author information[/h] 1 Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention (CDC), Atlanta, United States of America. 2 Battelle Memorial Institute, Atlanta, United States of America.
[h=3]Abstract[/h] Susceptibility of influenza A viruses to baloxavir can be affected by changes at amino acid residue 38 in polymerase acidic (PA) protein. Information on replicative fitness of PA-I38-substituted viruses remains sparse. We demonstrated that substitutions I38L/M/S/T not only had a differential effect on baloxavir susceptibility (9- to 116-fold), but also on in vitro replicative fitness. While I38L conferred undiminished growth, other substitutions led to mild attenuation. In a ferret model, control viruses outcompeted those carrying I38M or I38T substitutions, although their advantage was limited. These findings offer insights into the attributes of baloxavir resistant viruses needed for informed risk assessment.
Published by Oxford University Press for the Infectious Diseases Society of America 2019. This work is written by (a) US Government employee(s) and is in the public domain in the US.
[h=4]KEYWORDS:[/h] Cap-dependent endonuclease inhibitor; antiviral; baloxavir acid; drug resistance; ferret; influenza; polymerase acidic protein; replicative fitness
PMID: 31541547 DOI: 10.1093/infdis/jiz472
[h=1]Replicative fitness of seasonal influenza A viruses with decreased susceptibility to baloxavir.[/h] Chesnokov A[SUP]1[/SUP], Patel MC[SUP]1,[/SUP][SUP]2[/SUP], Mishin VP[SUP]1[/SUP], De La Cruz JA[SUP]1,[/SUP][SUP]2[/SUP], Lollis L[SUP]1,[/SUP][SUP]2[/SUP], Nguyen HT[SUP]1,[/SUP][SUP]2[/SUP], Dugan V[SUP]1[/SUP], Wentworth DE[SUP]1[/SUP], Gubareva LV[SUP]1[/SUP].
[h=3]Author information[/h] 1 Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention (CDC), Atlanta, United States of America. 2 Battelle Memorial Institute, Atlanta, United States of America.
[h=3]Abstract[/h] Susceptibility of influenza A viruses to baloxavir can be affected by changes at amino acid residue 38 in polymerase acidic (PA) protein. Information on replicative fitness of PA-I38-substituted viruses remains sparse. We demonstrated that substitutions I38L/M/S/T not only had a differential effect on baloxavir susceptibility (9- to 116-fold), but also on in vitro replicative fitness. While I38L conferred undiminished growth, other substitutions led to mild attenuation. In a ferret model, control viruses outcompeted those carrying I38M or I38T substitutions, although their advantage was limited. These findings offer insights into the attributes of baloxavir resistant viruses needed for informed risk assessment.
Published by Oxford University Press for the Infectious Diseases Society of America 2019. This work is written by (a) US Government employee(s) and is in the public domain in the US.
[h=4]KEYWORDS:[/h] Cap-dependent endonuclease inhibitor; antiviral; baloxavir acid; drug resistance; ferret; influenza; polymerase acidic protein; replicative fitness
PMID: 31541547 DOI: 10.1093/infdis/jiz472