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Avian influenza viruses of the H6 subtype are prevalent in wild ducks and likely play an important role in the ecology of influenza viruses through reassortment with other avian influenza viruses. Yet, only 152 Vietnamese H6 virus sequences were available in GISAID (Global Initiative on Sharing All Influenza Data) prior to this study with the most recent sequences being from 2018. Through surveillance in Vietnamese live bird markets from 2018 to 2021, we identified 287 samples containing one or several H6 viruses and other influenza A virus subtypes, demonstrating a high rate of co-infections among birds in Vietnamese live bird markets. For the 132 H6 samples with unique influenza virus sequences, we conducted phylogenetic and genetic analyses. Most of the H6 viruses were similar to each other and closely related to other H6 viruses; however, signs of reassortment with other avian influenza viruses were evident. At the genetic level, the Vietnamese H6 viruses characterized in our study encode a single basic amino acid at the HA cleavage site, consistent with low pathogenicity in poultry. The Vietnamese H6 viruses analyzed here possess an amino acid motif in HA that confers binding to both avian- and human-type receptors on host cells, consistent with their ability to infect mammals. The frequent detection of H6 viruses in Vietnamese live bird markets, the high rate of co-infections of birds with different influenza viruses, and the dual receptor-binding specificity of these viruses warrant their close monitoring for potential infection and spread among mammals. [ABSTRACT FROM AUTHOR]

Several small animal models, including mice, Syrian hamsters, guinea pigs, and ferrets are used to study the pathogenicity, transmissibility, and antigenicity of seasonal and pandemic influenza viruses. Moreover, animal models are essential for vaccination and challenge studies to evaluate the immunogenicity and protective efficacy of new vaccines. However, authentic human influenza viruses do not always replicate efficiently in these animal models. Previously, we developed a high-yield A/Puerto Rico/8/34 (PR8-HY) vaccine virus backbone that conferred an increased virus yield to several seasonal influenza vaccines in eukaryotic cells and embryonated chicken eggs. Here, we show that this PR8-HY genetic backbone also increases the replication of several seasonal influenza viruses in Syrian hamsters compared to the authentic viruses. Therefore, the PR8-HY backbone is useful for animal studies to assess the biological properties of influenza viral HA and NA. [ABSTRACT FROM AUTHOR]

The post‐translational acetylation of lysine residues is found in many nonhistone proteins and is involved in a wide range of biological processes. Recently, we showed that the nucleoprotein of the influenza A virus is acetylated by histone acetyltransferases (HATs), a phenomenon that affects viral transcription. Here, we report that the PA subunit of influenza A virus RNA‐dependent RNA polymerase is acetylated by the HATs, P300/CREB‐binding protein‐associated factor (PCAF), and general control nonderepressible 5 (GCN5), resulting in accelerated endonuclease activity. Specifically, the full‐length PA subunit expressed in cultured 293T cells was found to be strongly acetylated. Moreover, the partial recombinant protein of the PA N‐terminal region containing the endonuclease domain was also acetylated by PCAF and GCN5 in vitro, which facilitated its endonuclease activity. Mass spectrometry analyses identified K19 as a candidate acetylation target in the PA N‐terminal region. Notably, the substitution of the lysine residue at position 19 with glutamine, a mimic of the acetyl‐lysine residue, enhanced its endonuclease activity in vitro; this point mutation also accelerated influenza A virus RNA‐dependent RNA polymerase activity in the cell. Our findings suggest that PA acetylation is important for the regulation of the endonuclease and RNA polymerase activities of the influenza A virus. [ABSTRACT FROM AUTHOR]