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  1. Article ; Online: Sarbecovirus ORF6 proteins hamper induction of interferon signaling

    Izumi Kimura / Yoriyuki Konno / Keiya Uriu / Kristina Hopfensperger / Daniel Sauter / So Nakagawa / Kei Sato

    Cell Reports, Vol 34, Iss 13, Pp 108916- (2021)

    2021  

    Abstract: Summary: The presence of an ORF6 gene distinguishes sarbecoviruses such as severe acute respiratory syndrome coronavirus (SARS-CoV) and SARS-CoV-2 from other betacoronaviruses. Here we show that ORF6 inhibits induction of innate immune signaling, ... ...

    Abstract Summary: The presence of an ORF6 gene distinguishes sarbecoviruses such as severe acute respiratory syndrome coronavirus (SARS-CoV) and SARS-CoV-2 from other betacoronaviruses. Here we show that ORF6 inhibits induction of innate immune signaling, including upregulation of type I interferon (IFN) upon viral infection as well as type I and III IFN signaling. Intriguingly, ORF6 proteins from SARS-CoV-2 lineages are more efficient antagonists of innate immunity than their orthologs from SARS-CoV lineages. Mutational analyses identified residues E46 and Q56 as important determinants of the antagonistic activity of SARS-CoV-2 ORF6. Moreover, we show that the anti-innate immune activity of ORF6 depends on its C-terminal region and that ORF6 inhibits nuclear translocation of IRF3. Finally, we identify naturally occurring frameshift/nonsense mutations that result in an inactivating truncation of ORF6 in approximately 0.2% of SARS-CoV-2 isolates. Our findings suggest that ORF6 contributes to the poor IFN activation observed in individuals with coronavirus disease 2019 (COVID-19).
    Keywords SARS-CoV-2 ; COVID-19 ; ORF6 ; type I interferon ; type III interferon ; interferon-stimulated gene ; Biology (General) ; QH301-705.5
    Subject code 570
    Language English
    Publishing date 2021-03-01T00:00:00Z
    Publisher Elsevier
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: SARS-CoV-2 ORF3b Is a Potent Interferon Antagonist Whose Activity Is Increased by a Naturally Occurring Elongation Variant

    Yoriyuki Konno / Izumi Kimura / Keiya Uriu / Masaya Fukushi / Takashi Irie / Yoshio Koyanagi / Daniel Sauter / Robert J. Gifford / So Nakagawa / Kei Sato

    Cell Reports, Vol 32, Iss 12, Pp 108185- (2020)

    2020  

    Abstract: Summary: One of the features distinguishing SARS-CoV-2 from its more pathogenic counterpart SARS-CoV is the presence of premature stop codons in its ORF3b gene. Here, we show that SARS-CoV-2 ORF3b is a potent interferon antagonist, suppressing the ... ...

    Abstract Summary: One of the features distinguishing SARS-CoV-2 from its more pathogenic counterpart SARS-CoV is the presence of premature stop codons in its ORF3b gene. Here, we show that SARS-CoV-2 ORF3b is a potent interferon antagonist, suppressing the induction of type I interferon more efficiently than its SARS-CoV ortholog. Phylogenetic analyses and functional assays reveal that SARS-CoV-2-related viruses from bats and pangolins also encode truncated ORF3b gene products with strong anti-interferon activity. Furthermore, analyses of approximately 17,000 SARS-CoV-2 sequences identify a natural variant in which a longer ORF3b reading frame was reconstituted. This variant was isolated from two patients with severe disease and further increased the ability of ORF3b to suppress interferon induction. Thus, our findings not only help to explain the poor interferon response in COVID-19 patients but also describe the emergence of natural SARS-CoV-2 quasispecies with an extended ORF3b gene that may potentially affect COVID-19 pathogenesis.
    Keywords SARS-CoV-2 ; COVID-19 ; ORF3b ; type I interferon ; evolution ; Biology (General) ; QH301-705.5
    Subject code 610
    Language English
    Publishing date 2020-09-01T00:00:00Z
    Publisher Elsevier
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article ; Online: The SARS-CoV-2 spike S375F mutation characterizes the Omicron BA.1 variant

    Izumi Kimura / Daichi Yamasoba / Hesham Nasser / Jiri Zahradnik / Yusuke Kosugi / Jiaqi Wu / Kayoko Nagata / Keiya Uriu / Yuri L. Tanaka / Jumpei Ito / Ryo Shimizu / Toong Seng Tan / Erika P. Butlertanaka / Hiroyuki Asakura / Kenji Sadamasu / Kazuhisa Yoshimura / Takamasa Ueno / Akifumi Takaori-Kondo / Gideon Schreiber /
    Mako Toyoda / Kotaro Shirakawa / Takashi Irie / Akatsuki Saito / So Nakagawa / Terumasa Ikeda / Kei Sato

    iScience, Vol 25, Iss 12, Pp 105720- (2022)

    2022  

    Abstract: Summary: Recent studies have revealed the unique virological characteristics of Omicron, particularly those of its spike protein, such as less cleavage efficacy in cells, reduced ACE2 binding affinity, and poor fusogenicity. However, it remains unclear ... ...

    Abstract Summary: Recent studies have revealed the unique virological characteristics of Omicron, particularly those of its spike protein, such as less cleavage efficacy in cells, reduced ACE2 binding affinity, and poor fusogenicity. However, it remains unclear which mutation(s) determine these three virological characteristics of Omicron spike. Here, we show that these characteristics of the Omicron spike protein are determined by its receptor-binding domain. Of interest, molecular phylogenetic analysis revealed that acquisition of the spike S375F mutation was closely associated with the explosive spread of Omicron in the human population. We further elucidated that the F375 residue forms an interprotomer pi-pi interaction with the H505 residue of another protomer in the spike trimer, conferring the attenuated cleavage efficiency and fusogenicity of Omicron spike. Our data shed light on the evolutionary events underlying the emergence of Omicron at the molecular level.
    Keywords Molecular biology ; Virology ; Science ; Q
    Subject code 612
    Language English
    Publishing date 2022-12-01T00:00:00Z
    Publisher Elsevier
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  4. Article ; Online: Convergent evolution of SARS-CoV-2 Omicron subvariants leading to the emergence of BQ.1.1 variant

    Jumpei Ito / Rigel Suzuki / Keiya Uriu / Yukari Itakura / Jiri Zahradnik / Kanako Terakado Kimura / Sayaka Deguchi / Lei Wang / Spyros Lytras / Tomokazu Tamura / Izumi Kida / Hesham Nasser / Maya Shofa / Mst Monira Begum / Masumi Tsuda / Yoshitaka Oda / Tateki Suzuki / Jiei Sasaki / Kaori Sasaki-Tabata /
    Shigeru Fujita / Kumiko Yoshimatsu / Hayato Ito / Naganori Nao / Hiroyuki Asakura / Mami Nagashima / Kenji Sadamasu / Kazuhisa Yoshimura / Yuki Yamamoto / Tetsuharu Nagamoto / Jin Kuramochi / Gideon Schreiber / Akatsuki Saito / Keita Matsuno / Kazuo Takayama / Takao Hashiguchi / Shinya Tanaka / Takasuke Fukuhara / Terumasa Ikeda / Kei Sato

    Nature Communications, Vol 14, Iss 1, Pp 1-

    2023  Volume 20

    Abstract: Abstract In late 2022, various Omicron subvariants emerged and cocirculated worldwide. These variants convergently acquired amino acid substitutions at critical residues in the spike protein, including residues R346, K444, L452, N460, and F486. Here, we ... ...

    Abstract Abstract In late 2022, various Omicron subvariants emerged and cocirculated worldwide. These variants convergently acquired amino acid substitutions at critical residues in the spike protein, including residues R346, K444, L452, N460, and F486. Here, we characterize the convergent evolution of Omicron subvariants and the properties of one recent lineage of concern, BQ.1.1. Our phylogenetic analysis suggests that these five substitutions are recurrently acquired, particularly in younger Omicron lineages. Epidemic dynamics modelling suggests that the five substitutions increase viral fitness, and a large proportion of the fitness variation within Omicron lineages can be explained by these substitutions. Compared to BA.5, BQ.1.1 evades breakthrough BA.2 and BA.5 infection sera more efficiently, as demonstrated by neutralization assays. The pathogenicity of BQ.1.1 in hamsters is lower than that of BA.5. Our multiscale investigations illuminate the evolutionary rules governing the convergent evolution for known Omicron lineages as of 2022.
    Keywords Science ; Q
    Subject code 612
    Language English
    Publishing date 2023-05-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  5. Article ; Online: A role for gorilla APOBEC3G in shaping lentivirus evolution including transmission to humans.

    Yusuke Nakano / Keisuke Yamamoto / Mahoko Takahashi Ueda / Andrew Soper / Yoriyuki Konno / Izumi Kimura / Keiya Uriu / Ryuichi Kumata / Hirofumi Aso / Naoko Misawa / Shumpei Nagaoka / Soma Shimizu / Keito Mitsumune / Yusuke Kosugi / Guillermo Juarez-Fernandez / Jumpei Ito / So Nakagawa / Terumasa Ikeda / Yoshio Koyanagi /
    Reuben S Harris / Kei Sato

    PLoS Pathogens, Vol 16, Iss 9, p e

    2020  Volume 1008812

    Abstract: The APOBEC3 deaminases are potent inhibitors of virus replication and barriers to cross-species transmission. For simian immunodeficiency virus (SIV) to transmit to a new primate host, as happened multiple times to seed the ongoing HIV-1 epidemic, the ... ...

    Abstract The APOBEC3 deaminases are potent inhibitors of virus replication and barriers to cross-species transmission. For simian immunodeficiency virus (SIV) to transmit to a new primate host, as happened multiple times to seed the ongoing HIV-1 epidemic, the viral infectivity factor (Vif) must be capable of neutralizing the APOBEC3 enzymes of the new host. Although much is known about current interactions of HIV-1 Vif and human APOBEC3s, the evolutionary changes in SIV Vif required for transmission from chimpanzees to gorillas and ultimately to humans are poorly understood. Here, we demonstrate that gorilla APOBEC3G is a factor with the potential to hamper SIV transmission from chimpanzees to gorillas. Gain-of-function experiments using SIVcpzPtt Vif revealed that this barrier could be overcome by a single Vif acidic amino acid substitution (M16E). Moreover, degradation of gorilla APOBEC3F is induced by Vif through a mechanism that is distinct from that of human APOBEC3F. Thus, our findings identify virus adaptations in gorillas that preceded and may have facilitated transmission to humans.
    Keywords Immunologic diseases. Allergy ; RC581-607 ; Biology (General) ; QH301-705.5
    Language English
    Publishing date 2020-09-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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