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 IV mutation literature information.


  Treatment-Emergent Influenza Variant Viruses With Reduced Baloxavir Susceptibility: Impact on Clinical and Virologic Outcomes in Uncomplicated Influenza.
 PMID: 31309975       2020       The Journal of infectious diseases
Abstract: BACKGROUND: Single-dose baloxavir rapidly reduces influenza virus titers and symptoms in patients with uncomplicated influenza, but viruses with reduced in vitro susceptibility due to amino acid substitutions at position 38 of polymerase acidic protein (PA/I38X) sometimes emerge.
Abstract: CONCLUSIONS: The emergence of viruses with PA/I38X substitutions following baloxavir treatment was associated with transient rises in infectious virus titers, prolongation of virus detectability, initial delay in symptom alleviation, and uncommonly with symptom rebound.
Abstract: Median time to sustained cessation of infectious virus detection was 192, 48, and 96 hours in the baloxavir recipients with PA/I38X


  Identification of antigenic epitopes in the haemagglutinin protein of H7 avian influenza virus.
 PMID: 31508993       2020       Avian pathology
Abstract: The epitope 103RESGSS107 was highly conserved among Eurasian lineage strains of H7 AIV, whereas three amino acid substitutions (E104R, E104K and E104G) in the epitope occurred in 98.44% of North-American lineage strains.


  Oseltamivir Resistance in Severe Influenza A(H1N1)pdm09 Pneumonia and Acute Respiratory Distress Syndrome: A French Multicenter Observational Cohort Study.
 PMID: 31538643       2020       Clinical infectious diseases
Abstract: In a multicenter cohort study including 22 oseltamivir-treated patients with influenza A(H1N1)pdm09 acute respiratory distress syndrome, prevalence of the H275Y substitution in the neuraminidase, responsible for highly reduced sensitivity to oseltamivir, was 23%.
Abstract: Patients infected with the H275Y mutant virus had higher day 28 mortality than others (80% vs 12%; P = .011).


  Baloxavir Marboxil in Japanese Pediatric Patients With Influenza: Safety and Clinical and Virologic Outcomes.
 PMID: 31538644       2020       Clinical infectious diseases
Abstract: Among patients with PA/I38T/M-substituted virus emergence, those with baseline hemagglutinin inhibition (HAI) antibody titer <40 experienced delay in time to illness alleviation (median, 85.4 vs 56.0 hours in patients with higher baseline HAI antibody titer).
Abstract: CONCLUSIONS: A single, oral dose of baloxavir marboxil was well tolerated and rapidly reduced viral titers, but the common emergence of PA/I38T/M-substituted viruses warrants consideration of alternative dosing regimens in young children.
Abstract: Emergence was associated with longer infectious virus detectability (median time, 180.0 hours) and time to illness alleviation (median, 79.6 vs 42.8 hours in patients without PA/I38T/M-substituted viruses).|m


  Genetic Characterization of a Novel Reassortant H5N6 Avian Influenza Virus Identified from a 10-Year-Old Girl.
 PMID: 31666492       2020       Japanese journal of infectious diseases
Abstract: Q226L and G228S mutations were not observed, but S128P, S137A, and T160A substitutions were identified in the receptor binding sites.
Abstract: The resistance mutation D198N in the neuraminidase (NA) protein was also identified in this strain.


  Discovery of M2 channel blockers targeting the drug-resistant double mutants M2-S31N/L26I and M2-S31N/V27A from the influenza A viruses.
 PMID: 31669761       2020       European journal of pharmaceutical sciences
Abstract: In this study, we identified four amantadine-resistant M2 mutants among avian and human influenza A H5N1 strains circulating between 2002 and 2019: the single S31N and V27A mutants, and the S31N/L26I and S31N/V27A double mutants.
Abstract: Three compounds 6, 7, and 15 were found to significantly block all three M2 mutants: M2-S31N, M2-S31N/L26I, and M2-S31N/V27A.
Abstract: Using r


  Hemagglutinin Stability Regulates H1N1 Influenza Virus Replication and Pathogenicity in Mice by Modulating Type I Interferon Responses in Dendritic Cells.
 PMID: 31694942       2020       Journal of virology
Abstract: Here, we investigated the mechanisms by which a destabilizing HA mutation, Y17H (activation pH, 6.0), attenuates virus replication and pathogenicity in DBA/2 mice compared to wild-type (WT) virus (activation pH, 5.5).
Abstract: In contrast, the HA-Y17H mutation reduced virus replication in murine airway murine nasal epithelial cell and murine tracheal epithelial cell cultures and attenuated virus replication, virus spread, the severity of infection, and cellular infiltration in the lungs of mice.
Abstract: Normalizing virus infection and weight loss in mice by inoculating them with Y17H virus at a dose 500-fold higher than that of WT virus revealed that the destabilized mutant virus triggered the upregulation of more host genes and increased type I IFN responses and cytokine expression in DBA/2 mouse lu


  High genetic stability in MDCK-SIAT1 passaged human influenza viruses.
 PMID: 30241880       2019       Journal of infection and chemotherapy
Abstract: NA D151G/N changes were not seen in any of the MDCK-SIAT1 passaged A/H3N2 viruses, even in the small variants analysis conducted using deep sequencing.
Abstract: MDCK-induced amino acid (AA) mutation, such as D151G/N in the neuraminidase (NA) of influenza A/H3N2 viruses, is of concern.


  Amino Acid Residue 217 in the Hemagglutinin Glycoprotein Is a Key Mediator of Avian Influenza H7N9 Virus Antigenicity.
 PMID: 30282714       2019       Journal of virology
Abstract: The HA gene sequences of viruses recovered after the fifth passage showed that the viruses readily acquired mutations at three different amino acid positions (A125T, A151T, and L217Q).
Abstract: The analysis showed that the emergent immune escape viruses contained mutations A125T, A151T, and L217Q in the hemagglutinin (HA) glycoprotein as early as passage 5 and that these mutations persisted until passage 10.
Abstract: The results revealed that a single mutation, L217Q, in the HA of H7N9 virus led to 23- and 8-fold reductions in hemagglutination inhibition (HI) titer with ferret and chick


  Molecular epidemiology of the hemagglutinin gene of prevalent influenza virus A/H1N1/pdm09 among patient in Iran.
 PMID: 30336188       2019       Virus research
Abstract: Phylogenetic analysis of the HA genes of the A/H1N1pdm09 viruses revealed the circulation of clade 6B1, characterized by amino acid substitutions S84N, S162N and I216T, where position 162 became glycosylated.



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