Replicative Fitness of Seasonal Influenza A Viruses With Decreased Susceptibility to Baloxavir

Details

• Alternative Title:
  J Infect Dis
• Personal Author:
  Chesnokov, Anton ; Patel, Mira C. ; Mishin, Vasiliy P. ; De La Cruz, Juan A. ; Lollis, Lori ; Nguyen, Ha T. ; Dugan, Vivien ; Wentworth, David E. ; Gubareva, Larisa V.
• Description:
  Susceptibility of influenza A viruses to baloxavir can be affected by changes at amino acid residue 38 in the 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. Although 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.
• Subjects:
  Amino Acid Substitution Animals Antiviral Agents Article Baloxavir Acid Dibenzothiepins Disease Models, Animal Dogs Drug Resistance Drug Resistance, Viral Ferret Ferrets High-Throughput Nucleotide Sequencing Influenza Influenza A Virus, H1N1 Subtype Influenza A Virus, H3N2 Subtype Madin Darby Canine Kidney Cells Male Microbial Sensitivity Tests Morpholines Orthomyxoviridae Infections Oxazines Polymerase Acidic Protein Pyridines Pyridones RNA-Dependent RNA Polymerase Seasons Thiepins Treatment Outcome Triazines Viral Proteins Virus Replication

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• Source:
  J Infect Dis. 221(3):367-371
• Pubmed ID:
  31541547
• Pubmed Central ID:
  PMC8851376
• Document Type:
  Journal Article
• Funding:
  CC999999/ImCDC/Intramural CDC HHSUnited States/
• Volume:
  221
• Issue:
  3
• Collection(s):
  CDC Public Access
• Main Document Checksum:
  urn:sha256:32338d51622c1fa1a8c4706da7f3a7c4e86ff8dc437bddafd5d93e626258f50c
• Download URL:
  https://stacks.cdc.gov/view/cdc/114582/cdc_114582_DS1.pdf
• File Type:
  [PDF - 383.70 KB ]