Mutations in the H7 HA and PB1 genes of avian influenza a viruses increase viral pathogenicity and contact transmission in guinea pigs

Dreier, Carola; Resa-Infante, Patricia; Thiele, Swantje; Stanelle-Bertram, Stephanie; Walendy-Gnirß, Kerstin; Speiseder, Thomas; Preuß, Annette; Müller, Zacharias; Klenk, Hans‐Dieter; Stech, Jürgen; Gabriel, Gülşah

doi:10.1080/22221751.2019.1663131

Cited by 7 publications

(6 citation statements)

References 35 publications

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“…7 Mutations in the polymerase genes of viruses are reported to enhance their virulence. [8][9][10] Mutations in the RdRp gene sequence were first reported in virus isolates from Europe in February 2020, and then in virus isolates from North America in March 2020. 2 In particular, a mutation at position 14408, which leads to an amino acid substitution (P323L) in RdRp, was identified as a mutation hotspot, and in silico analysis suggests that this change may affect stability of the tertiary complex of RdRp.…”

Section: Introductionmentioning

confidence: 99%

Mutations in SARS‐CoV‐2 nsp7 and nsp8 proteins and their predicted impact on replication/transcription complex structure

Reshamwala

Likhite

Degani

et al. 2021

Journal of Medical Virology

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Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) RNA‐dependent RNA polymerase (RdRp) has been identified to be a mutation hot spot, with the P323L mutation being commonly observed in viral genomes isolated from North America. RdRp forms a complex with nonstructural proteins nsp7 and nsp8 to form the minimal replication/transcription machinery required for genome replication. As mutations in RdRp may affect formation of the RdRp–nsp7–nsp8 supercomplex, we analyzed viral genomes to identify mutations in nsp7 and nsp8 protein sequences. Based on in silico analysis of predicted structures of the supercomplex comprising of native and mutated proteins, we demonstrate that specific mutations in nsp7 and nsp8 proteins may have a role in stabilization of the replication/transcription complex.

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Section: Introductionmentioning

confidence: 99%

Mutations in SARS‐CoV‐2 nsp7 and nsp8 proteins and their predicted impact on replication/transcription complex structure

Reshamwala

Likhite

Degani

et al. 2021

Journal of Medical Virology

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“…Lina et al employed guinea pigs to show that adaptive amino acid substitutions account for the increased transmissibility of H9N2 avian influenza virus [109]. Mutations in the HA and PB1 genes were also demonstrated to increase pathogenicity and transmissibility of influenza viruses in the guinea pig model [110,111]. Previous studies using guinea pigs have shown that IAVs are transmissible via aerosolized fomites, microscopic particulates released from virus-contaminated surfaces (such as fur, skin, or bedding) [112], or respiratory droplets [113].…”

Section: Guinea Pig Modelmentioning

confidence: 99%

Animal Models for Influenza Research: Strengths and Weaknesses

Nguyen

Rollon

Choi

2021

Viruses

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Influenza remains one of the most significant public health threats due to its ability to cause high morbidity and mortality worldwide. Although understanding of influenza viruses has greatly increased in recent years, shortcomings remain. Additionally, the continuous mutation of influenza viruses through genetic reassortment and selection of variants that escape host immune responses can render current influenza vaccines ineffective at controlling seasonal epidemics and potential pandemics. Thus, there is a knowledge gap in the understanding of influenza viruses and a corresponding need to develop novel universal vaccines and therapeutic treatments. Investigation of viral pathogenesis, transmission mechanisms, and efficacy of influenza vaccine candidates requires animal models that can recapitulate the disease. Furthermore, the choice of animal model for each research question is crucial in order for researchers to acquire a better knowledge of influenza viruses. Herein, we reviewed the advantages and limitations of each animal model—including mice, ferrets, guinea pigs, swine, felines, canines, and non-human primates—for elucidating influenza viral pathogenesis and transmission and for evaluating therapeutic agents and vaccine efficacy.

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“…Вирусы ВПГП подтипа Н5 способны инфицировать человека, несмотря на то что их гемагглютинин преиму щественно взаимодействует с клеточными рецептора ми SAα2,3gal. Однако при успешной репродукции ви руса гриппа в клетках млекопитающих исследователи выявляли мутации в других вирусных генах, которые предполагаются как маркеры адаптации вируса гриппа для размножения в организме млекопитающих [6][7][8][9][10][11]…”

Section: Conflict Of Interestunclassified

Analysis of marker substitutions in A/chicken/Astrakhan/2171-1/2020 H5N8 isolate of avian influenza virus recovered in the Astrakhan Oblast

Зиняков¹,

Андриясов²,

Овчинникова³

et al. 2021

Veterinariâ segodnâ

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At the end of 2020, a large-scale bird death was registered at one of the poultry farms in the Astrakhan region, the cause of which was avian influenza. Data on detection of the marker substitutions in viral proteins of avian influenza virus A/chicken/Astrakhan/2171-1/2020 isolate are presented in the paper. Type A Н5N8 avian influenza virus was identified with complex PCR-based methods in the submitted samples. Hemagglutinin gene fragment sequencing identified REKRRKR/ GLF, highly pathogenic avian influenza virus isolate-characteristic amino acid sequence of the hemagglutinin cleavage site. Phylogenetic analysis of nucleotide sequences of hemagglutinin gene segment (848–1105 bp ORF) allowed A/chicken/Astrakhan/2171-1/2020 H5N8 isolate to be classified to highly pathogenic avian influenza virus genetic clade 2.3.4.4. Comparative analysis of genome segments using available databases showed that A/chicken/Astrakhan/2171-1/2020 H5N8 virus related to А/Н5 avian influenza virus isolates detected in the Russian Federation in 2016–2020. Analysis of the studied virus isolate hemagglutinin amino acid identified AIV-characteristic G225QRG228 amino acids in the receptor-binding domain of the protein enabling high-affinity binding to avian epithelial cell SAα-2,3- gal receptors. Single mutations, 70G in NEP protein and 13Р in PB1 protein, out of the list of the reported influenza virus mutations affecting successful influenza virus replication in mammals were identified. No mutations affecting virus sensitivity to anti-viral medicines, rimantadin, amantadine, oseltamivir and zanamivir, were detected. The following mutations recognized as pathogenicity determinants in mice were found: 42S in the NS1 protein and 30D protein 215A in M1 protein.

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Mutations in the H7 HA and PB1 genes of avian influenza a viruses increase viral pathogenicity and contact transmission in guinea pigs

Cited by 7 publications

References 35 publications

Mutations in SARS‐CoV‐2 nsp7 and nsp8 proteins and their predicted impact on replication/transcription complex structure

Mutations in SARS‐CoV‐2 nsp7 and nsp8 proteins and their predicted impact on replication/transcription complex structure

Animal Models for Influenza Research: Strengths and Weaknesses

Analysis of marker substitutions in A/chicken/Astrakhan/2171-1/2020 H5N8 isolate of avian influenza virus recovered in the Astrakhan Oblast

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