Abstract: From examining the protein alignments, we found several residue changes in the seal virus that did not occur in the bird viruses, including D701N in the PB2 segment, a rare mutation, and a hallmark of mammalian adaptation of bird viruses.
Discussion: D701N is common in canine and horse H3N8 IAV (see Supplementary Table S4), but does not occur in birds, and was found associated with highly-pathogenic H5N1 viruses which infected humans.
Discussion: D701N mutation was also found in the A/harbor_seal/Massachusetts/1/2011, but not in the H10N7 outbreak, despite sustained transmission in seals for several months, nor in any other previously sequenced seal PB2 genes.
Discussion: This likely indicates adaptation to the seal environment, a hypothesis supported by the occurrence of the PMID: 32215564
2020
The Journal of infectious diseases
Abstract: Circulating 3C.2a viruses showed considerable diversity in the hemagglutinin glycoprotein and the egg-adapted vaccine strain also bore mutations, notably T160K loss-of-glycosylation.
N-benzyl 4,4-disubstituted piperidines as a potent class of influenza H1N1 virus inhibitors showing a novel mechanism of hemagglutinin fusion peptide interaction.
PMID: 32220685
2020
European journal of medicinal chemistry
Abstract: Furthermore, the HA1-S326V mutation resulting in resistance to 2 is close to the proposed new binding pocket.
Insertion of Basic Amino Acids in the Hemagglutinin Cleavage Site of H4N2 Avian Influenza Virus (AIV)-Reduced Virus Fitness in Chickens is Restored by Reassortment with Highly Pathogenic H5N1 AIV.
PMID: 32231159
2020
International journal of molecular sciences
Abstract: Efficient cell culture replication of T327R/K carrying H4N2 viruses increased by treatment with trypsin, particularly in MDCK cells, and reassortment with HPAIV H5N1.
Abstract: Here, we investigated the virulence of this virus in chickens after expansion of the polybasic CS by substitution of T327R (322PEKRRRR/G329) or T327K (322PEKRRKR/G329) with or without reassortment with HPAIV H5N1 and H7N7.
Method: For TMPRSS2 and HAT, HEK293T cells that do not express an endogenous HAT or TMPRSS2, were co-transfected with 1 microg pCAGGS plasmids containing H4N2_T327K, as well as 10 ng plasmid coding for each protease in the presence or absence of 50 microM furin inhibitior MI-1148 (kindly provided by Torsten Steinmetzer, Institute of Pharmaceutical Chemistry, Philipps-University Marburg, Marburg, Germany).
Method: Furthermore,
Treatment-Emergent Influenza Virus Polymerase Acidic Substitutions Independent of Those at I38 Associated With Reduced Baloxavir Susceptibility and Virus Rebound in Trials of Baloxavir Marboxil.
PMID: 32253432
2020
The Journal of infectious diseases
Abstract: Influenza viruses harboring treatment-emergent I38F/M/N/T substitutions in the polymerase acidic (PA) endonuclease exhibited reduced susceptibility to baloxavir and were associated with virus rebound and variable clinical response in clinical trials.
Abstract: US regulatory review of registrational trial data also identified treatment-emergent PA substitutions E23K in A/H1N1 viruses and E23G/K, A37T, and E199G in A/H3N2 viruses, which conferred reduced susceptibility to baloxavir, although to a lesser degree than I38F/M/N/T substitutions, and were associated with virus rebound.
Baloxavir Marboxil 2% Granules in Japanese Children With Influenza: An Open-label Phase 3 Study.
PMID: 32433222
2020
The Pediatric infectious disease journal
Discussion: Age-based analyses showed that young children with PA/I38X-substituted virus had longer TTIA and some also had co-infections with other viruses (Figure, Supplemental Digital Content 8, http://links.lww.com/INF/D975), which were also observed in the miniSTONE-2 study.
Discussion: In children with fever resolution before day 4, fever recurrence was observed in approximately 60% of children with PA/I38X-substituted virus or influenza B after day 4, although fever resolved again during the 14-day observation period (Figure, Supplemental Digital Content 7B, http://links.lww.com/INF/D974).
Discussion: In the current study, 5 children (19.2% of 26 children with paired sequence data available) were identified as having PA/I38X-substituted virus.
Discussion: Increas
Laninamivir-Interferon Lambda 1 Combination Treatment Promotes Resistance by Influenza A Virus More Rapidly than Laninamivir Alone.
PMID: 32393488
2020
Antimicrobial agents and chemotherapy
Abstract: Moreover, the E119G NA mutation emerged together with concomitant hemagglutinin (HA) mutations (T197A and D222G), which were selected more rapidly by combination treatment with laninamivir plus IFN-lambda1 (passages 2 and 3, respectively) than by laninamivir alone (passage 10).
Abstract: Surprisingly, laninamivir used in combination with IFN-lambda1 promoted the emergence of the E119G NA mutation five passages earlier than laninamivir alone (passage 2 versus passage 7, respectively).
mRNA display with library of even-distribution reveals cellular interactors of influenza virus NS1.
Abstract: We also use md-LED to identify a mutant of NS1, D92Y, results in a loss of interaction with CPSF1.
Introduction: In addition, we explore the use of md-LED to examine the differential cellular binders of wild-type NS1 and a point mutant, D92Y, which had been previously shown to weaken NS1's known function in disrupting the interferon response.
Introduction: We find that the D92Y mutant failed to engage CPSF1, likely resulting in an increased host response.
Meth
Method: HA-tagged WT or D92Y mutant NS1 protein was expressed in 293T cells, lysed at 2 days post transfection and bound with anti-HA overnight at 4 C.
Substitutions in the PB2 methionine 283 residue affect H5 subtype avian influenza virus virulence.
PMID: 32351035
2020
Transboundary and emerging diseases
Abstract: The substitution PB2-M283I had an opposite phenotype.
Abstract: The substitution PB2-M283L displayed high virulence, resulting in a greater virus load in different tissues, more severe histopathological lesions and proinflammatory cytokines burst in mice.
Abstract: The substitution PB2-M283L enhanced the growth capacity and polymerase activity in human and mammalian cells in comparison to the rWT virus.
Baloxavir for the treatment of Influenza in allogeneic hematopoietic stem cell transplant recipients previously treated with oseltamivir.
Abstract: Of the three patients infected with wild-type influenza virus, two cleared the virus after baloxavir treatment, while the third patient developed the polymerase I38T variant linked to baloxavir resistance.
Abstract: RESULTS: Two patients were infected with influenza A/H1pdm09 carrying a neuraminidase variant (H275Y) linked to oseltamivir resistance.
IV mutation literature information.
PMID: 
2020
Virus evolution
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