PB2 and HA mutations increase the virulence of highly pathogenic H5N5 clade 2.3.4.4 avian influenza virus in mice

Yu, Zhijun; Cheng, Kaihui; Sun, Weiyang; Zhang, Xing-Hai; Xia, Xianzhu; Gao, Yuwei

doi:10.1007/s00705-017-3631-7

Cited by 10 publications

(9 citation statements)

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“…Adaptation of A/duck/Liaoning/LN/2011(H5N5) to mice resulted in virulence mutations PB2-E627K and HA2-F110L, which decreased MLD 50 values in mice 1000-fold and 3.16-fold, respectively [ 205 ]. Based on the position of HA2-F110L in the hinge region of the central triple-stranded core of the HA protein, the mutation has been speculated to alter HA stability.…”

Section: H5nxmentioning

confidence: 99%

Hemagglutinin Stability and Its Impact on Influenza A Virus Infectivity, Pathogenicity, and Transmissibility in Avians, Mice, Swine, Seals, Ferrets, and Humans

Russell

2021

Viruses

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Genetically diverse influenza A viruses (IAVs) circulate in wild aquatic birds. From this reservoir, IAVs sporadically cause outbreaks, epidemics, and pandemics in wild and domestic avians, wild land and sea mammals, horses, canines, felines, swine, humans, and other species. One molecular trait shown to modulate IAV host range is the stability of the hemagglutinin (HA) surface glycoprotein. The HA protein is the major antigen and during virus entry, this trimeric envelope glycoprotein binds sialic acid-containing receptors before being triggered by endosomal low pH to undergo irreversible structural changes that cause membrane fusion. The HA proteins from different IAV isolates can vary in the pH at which HA protein structural changes are triggered, the protein causes membrane fusion, or outside the cell the virion becomes inactivated. HA activation pH values generally range from pH 4.8 to 6.2. Human-adapted HA proteins tend to have relatively stable HA proteins activated at pH 5.5 or below. Here, studies are reviewed that report HA stability values and investigate the biological impact of variations in HA stability on replication, pathogenicity, and transmissibility in experimental animal models. Overall, a stabilized HA protein appears to be necessary for human pandemic potential and should be considered when assessing human pandemic risk.

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Section: H5nxmentioning

confidence: 99%

Hemagglutinin Stability and Its Impact on Influenza A Virus Infectivity, Pathogenicity, and Transmissibility in Avians, Mice, Swine, Seals, Ferrets, and Humans

Russell

2021

Viruses

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“…This set of protection seeks to safeguard the immune response of the host body in several ways, like the inhibition of interferon, latent infections, or the presence of fusion proteins in the viral capsid [90] . Besides, viruses can mutate and might result in more tropism and virulence, thus increasing the evasion from the immunologic system, aggravating the clinical condition of the host [92 , 93] .…”

Section: Virusmentioning

confidence: 99%

Biosensors for the detection of respiratory viruses: A review

Ribeiro¹,

Cordeiro²,

Freitas³

et al. 2020

Talanta Open

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Highlights A review containing the newest contributions of biosensors for respiratory viruses’ detection is presented. Influenza virus, coronavirus and respiratory syncytial virus were extensively analyzed. Tables containing biosensors information regarding the detection of the viruses are presented. Discussion based on the new trends and authors accomplishments are applied. SARS-CoV-2 biosensors already published were included and analyzed.

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“…Graef et al uncovered the PB2 subunit is a major virulence determinant of influenza viruses by interacting with the mitochondrial antiviral signaling protein and inhibiting expression of beta interferon (Graef et al, 2010). Yu et al found adaptive changes that confer increased virulence in mammals on HA and PB2 segments using generated mouse-adapted viruses (Yu et al, 2018). Our proposed model has further revealed the importance of PB2 and HA segments on the inference of virulence compared with other segments through computational analysis.…”

Section: Importance Of Single Segment-based Ensemble Cnn Modelmentioning

confidence: 99%

VirPreNet: A weighted ensemble convolutional neural network for the virulence prediction of influenza A virus using all 8 segments

Yin

Luo

Zhuang

et al. 2020

Preprint

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MotivationInfluenza viruses are persistently threatening public health, causing annual epidemics and sporadic pandemics. The evolution of influenza viruses remains to be the main obstacle in the effectiveness of antiviral treatments due to rapid mutations. Previous work has been investigated to reveal the determinants of virulence of the influenza A virus. To further facilitate flu surveillance, explicit detection of influenza virulence is crucial to protect public health from potential future pandemics.ResultsIn this paper, we propose a weighted ensemble convolutional neural network for the virulence prediction of influenza A viruses named VirPreNet that uses all 8 segments. Firstly, mouse lethal dose 50 is exerted to label the virulence of infections into two classes, namely avirulent and virulent. A numerical representation of amino acids named ProtVec is applied to the 8-segments in a distributed manner to encode the biological sequences. After splittings and embeddings of influenza strains, the ensemble convolutional neural network is constructed as the base model on the influenza dataset of each segment, which serves as the VirPreNet’s main part. Followed by a linear layer, the initial predictive outcomes are integrated and assigned with different weights for the final prediction. The experimental results on the collected influenza dataset indicate that VirPreNet achieves state-of-the-art performance combining ProtVec with our proposed architecture. It outperforms baseline methods on the independent testing data. Moreover, our proposed model reveals the importance of PB2 and HA segments on the virulence prediction. We believe that our model may provide new insights into the investigation of influenza virulence.Contactyinr0002@e.ntu.edu.sgAvailability and ImplementationCodes and data to generate the VirPreNet are publicly available at https://github.com/Rayin-saber/VirPreNet

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PB2 and HA mutations increase the virulence of highly pathogenic H5N5 clade 2.3.4.4 avian influenza virus in mice

Cited by 10 publications

References 50 publications

Hemagglutinin Stability and Its Impact on Influenza A Virus Infectivity, Pathogenicity, and Transmissibility in Avians, Mice, Swine, Seals, Ferrets, and Humans

Hemagglutinin Stability and Its Impact on Influenza A Virus Infectivity, Pathogenicity, and Transmissibility in Avians, Mice, Swine, Seals, Ferrets, and Humans

Biosensors for the detection of respiratory viruses: A review

VirPreNet: A weighted ensemble convolutional neural network for the virulence prediction of influenza A virus using all 8 segments

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