H7N9 Influenza A Virus Exhibits Importin-α7–Mediated Replication in the Mammalian Respiratory Tract

Bertram, Stephanie; Thiele, Swantje; Dreier, Carola; Resa-Infante, Patricia; Preuß, Annette; Riel, Debby van; Mok, Chris Ka Pun; Schwalm, Folker; Peiris, Malik; Klenk, Hans‐Dieter; Gabriel, Gülşah

doi:10.1016/j.ajpath.2016.12.017

Cited by 9 publications

(7 citation statements)

References 39 publications

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“…7 ). Moreover, previous studies demonstrated that importin-α7 was crucial for enhanced viral replication and severe damage in mice using importin-α7 knockout mice 27 – 29 . Therefore, future studies will be required to investigate the molecular mechanism of the enhanced viral replication and pathogenicity mediated by the D701N mutation using the importin-α7 knockout mouse model.…”

Section: Discussionmentioning

confidence: 99%

Substitution of D701N in the PB2 protein could enhance the viral replication and pathogenicity of Eurasian avian-like H1N1 swine influenza viruses

Liu

Zhu

Feng

et al. 2018

Emerging Microbes & Infections

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Eurasian avian-like H1N1 (EA H1N1) swine influenza viruses (SIVs) have become predominant in pig populations in China and have recently been reported to have the most potential to raise the next pandemic in humans. The mutation D701N in the PB2 protein, which accounts for 31% of H1N1 SIVs, has previously been shown to contribute to the adaptation of the highly pathogenic H5N1 or H7N7 avian influenza viruses in mammals. However, little is known of the effects of this substitution on the EA H1N1 viruses. Herein, we investigated the contributions of 701N in the PB2 protein to an EA H1N1 SIV (A/Hunan/42443/2015(H1N1), HuN EA-H1N1), which had 701D in the PB2 protein. Our results found that viral polymerase activity, viral replication, and pathogenicity in mice were indeed enhanced due to the introduction of 701N into the PB2 protein, and the increased viral growth was partly mediated by the host factor importin-α7. Thus, substantial attention should be paid to the D701N mutation in pig populations.

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Section: Discussionmentioning

confidence: 99%

Substitution of D701N in the PB2 protein could enhance the viral replication and pathogenicity of Eurasian avian-like H1N1 swine influenza viruses

Liu

Zhu

Feng

et al. 2018

Emerging Microbes & Infections

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“…Similarly, importin-α interacts to different NLSs on viral polymerase subunits to mediate the nuclear import of vRNP such as NLS at aa residues 449–495 and 738–755 of PB2 [ 202 ], NLS at aa residues 187–211 of PB1 [ 203 ] and NLS at aa residues 124–139, E154, 186–247 of PA [ 204 ]. Interestingly, 319K (NP), 701N (PB2), and 627K (PB2) are important to adapt the binding of vRNP from influenza virus of avian origin to mammalian importin-α7 isoform [ 205 , 206 , 207 , 208 ]. However, IAVs with the avian signatures (627E and 701D) depend primarily on importin-α3 [ 207 , 208 ].…”

Section: Viral Determinants For Zoonotic Potential Of Iavmentioning

confidence: 99%

Zoonotic Potential of Influenza A Viruses: A Comprehensive Overview

Mostafa

Mettenleiter

et al. 2018

Viruses

209

221

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Influenza A viruses (IAVs) possess a great zoonotic potential as they are able to infect different avian and mammalian animal hosts, from which they can be transmitted to humans. This is based on the ability of IAV to gradually change their genome by mutation or even reassemble their genome segments during co-infection of the host cell with different IAV strains, resulting in a high genetic diversity. Variants of circulating or newly emerging IAVs continue to trigger global health threats annually for both humans and animals. Here, we provide an introduction on IAVs, highlighting the mechanisms of viral evolution, the host spectrum, and the animal/human interface. Pathogenicity determinants of IAVs in mammals, with special emphasis on newly emerging IAVs with pandemic potential, are discussed. Finally, an overview is provided on various approaches for the prevention of human IAV infections.

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“…Importin-α7 additionally promotes virus replication by a yet unknown mechanism beyond nuclear transport, supporting high-level IAV replication in various mammalian, including human cells (3). Most importantly, it could be shown that mice lacking the importin-α7 gene can no longer support high-titer virus replication of PB2 627K or 701N adapted influenza strains in the murine respiratory tract, leading to up to 100% survival upon influenza challenge (3,(6)(7)(8).…”

Section: Introductionmentioning

confidence: 99%

ANP32B Deficiency Protects Mice From Lethal Influenza A Virus Challenge by Dampening the Host Immune Response

et al. 2020

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Deciphering complex virus-host interactions is crucial for pandemic preparedness. In this study, we assessed the impact of recently postulated cellular factors ANP32A and ANP32B of influenza A virus (IAV) species specificity on viral pathogenesis in a genetically modified mouse model. Infection of ANP32A −/− and ANP32A +/+ mice with a seasonal H3N2 IAV or a highly pathogenic H5N1 human isolate did not result in any significant differences in virus tropism, innate immune response or disease outcome. However, infection of ANP32B −/− mice with H3N2 or H5N1 IAV revealed significantly reduced virus loads, inflammatory cytokine response and reduced pathogenicity compared to ANP32B +/+ mice. Genome-wide transcriptome analyses in ANP32B +/+ and ANP32B −/− mice further uncovered novel immune-regulatory pathways that correlate with reduced pathogenicity in the absence of ANP32B. These data show that ANP32B but not ANP32A promotes IAV pathogenesis in mice. Moreover, ANP32B might possess a yet unknown immune-modulatory function during IAV infection. Targeting ANP32B or its regulated pathways might therefore pose a new strategy to combat severe influenza.

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H7N9 Influenza A Virus Exhibits Importin-α7–Mediated Replication in the Mammalian Respiratory Tract

Cited by 9 publications

References 39 publications

Substitution of D701N in the PB2 protein could enhance the viral replication and pathogenicity of Eurasian avian-like H1N1 swine influenza viruses

Substitution of D701N in the PB2 protein could enhance the viral replication and pathogenicity of Eurasian avian-like H1N1 swine influenza viruses

Zoonotic Potential of Influenza A Viruses: A Comprehensive Overview

ANP32B Deficiency Protects Mice From Lethal Influenza A Virus Challenge by Dampening the Host Immune Response

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