論文 - 齊藤 暁
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The SARS-CoV-2 Lambda variant exhibits enhanced infectivity and immune resistance. 査読あり
Kimura I, Kosugi Y, Wu J, Zahradnik J, Yamasoba D, Butlertanaka EP, Tanaka YL, Uriu K, Liu Y, Morizako N, Shirakawa K, Kazuma Y, Nomura R, Horisawa Y, Tokunaga K, Ueno T, Takaori-Kondo A, Schreiber G, Arase H, Genotype to Phenotype Japan (G2P-Japan) Consortium., Motozono C, Saito A, Nakagawa S, Sato K
Cell reports 38 ( 2 ) 110218 - 110218 2021年12月
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Enhanced fusogenicity and pathogenicity of SARS-CoV-2 Delta P681R mutation. 査読あり
Saito A, Irie T, Suzuki R, Maemura T, Nasser H, Uriu K, Kosugi Y, Shirakawa K, Sadamasu K, Kimura I, Ito J, Wu J, Iwatsuki-Horimoto K, Ito M, Yamayoshi S, Loeber S, Tsuda M, Wang L, Ozono S, Butlertanaka EP, Tanaka YL, Shimizu R, Shimizu K, Yoshimatsu K, Kawabata R, Sakaguchi T, Tokunaga K, Yoshida I, Asakura H, Nagashima M, Kazuma Y, Nomura R, Horisawa Y, Yoshimura K, Takaori-Kondo A, Imai M, Genotype to Phenotype Japan (G2P-Japan) Consortium., Tanaka S, Nakagawa S, Ikeda T, Fukuhara T, Kawaoka Y, Sato K
Nature 602 ( 7896 ) 300 - 306 2021年11月
担当区分：筆頭著者 記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Springer Science and Business Media LLC
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Yoshida T, Takemoto H, Sakamaki T, Tokuyama N, Hart J, Hart T, Dupain J, Cobden A, Mulavwa M, Hashimoto C, Isaji M, Kaneko A, Enomoto Y, Sato E, Kooriyama T, Miyabe-Nishiwaki T, Suzuki J, Saito A, Furuichi T, Akari H
Primates; journal of primatology 62 ( 6 ) 897 - 903 2021年8月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Springer Science and Business Media LLC
DOI： 10.1007/s10329-021-00935-5
その他リンク： https://link.springer.com/article/10.1007/s10329-021-00935-5/fulltext.html
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How Do Flaviviruses Hijack Host Cell Functions by Phase Separation? 査読あり
Akatsuki Saito, Maya Shofa, Hirotaka Ode, Maho Yumiya, Junki Hirano, Toru Okamoto, Shige H. Yoshimura
Viruses 13 ( 8 ) 1479 - 1479 2021年7月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：MDPI AG
Viral proteins interact with different sets of host cell components throughout the viral life cycle and are known to localize to the intracellular membraneless organelles (MLOs) of the host cell, where formation/dissolution is regulated by phase separation of intrinsically disordered proteins and regions (IDPs/IDRs). Viral proteins are rich in IDRs, implying that viruses utilize IDRs to regulate phase separation of the host cell organelles and augment replication by commandeering the functions of the organelles and/or sneaking into the organelles to evade the host immune response. This review aims to integrate current knowledge of the structural properties and intracellular localizations of viral IDPs to understand viral strategies in the host cell. First, the properties of viral IDRs are reviewed and similarities and differences with those of eukaryotes are described. The higher IDR content in viruses with smaller genomes suggests that IDRs are essential characteristics of viral proteins. Then, the interactions of the IDRs of flaviviruses with the MLOs of the host cell are investigated with emphasis on the viral proteins localized in the nucleoli and stress granules. Finally, the possible roles of viral IDRs in regulation of the phase separation of organelles and future possibilities for antiviral drug development are discussed.
DOI： 10.3390/v13081479
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SARS-CoV-2 B.1.617 mutations L452 and E484Q are not synergistic for antibody evasion 査読あり
Isabella Ferreira, Steven Kemp, Rawlings Datir, Akatsuki Saito, Bo Meng, Partha Rakshit, Akifumi Takaori-Kondo, Yusuke Kosugi, Keiya Uriu, Izumi Kimura, Kotaro Shirakawa, Adam Abdullahi, Anurag Agarwal, Seiya Ozono, Kenzo Tokunaga, Kei Sato, Ravindra K Gupta
The Journal of Infectious Diseases 2021年7月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Oxford University Press (OUP)
<title>Abstract</title>
The SARS-CoV-2 B.1.617 variant emerged in the Indian state of Maharashtra in late 2020. There have been fears that two key mutations seen in the receptor binding domain L452R and E484Q would have additive effects on evasion of neutralising antibodies. We report that spike bearing L452R and E484Q confers modestly reduced sensitivity to BNT162b2 mRNA vaccine-elicited antibodies following either first or second dose. The effect is similar in magnitude to the loss of sensitivity conferred by L452R or E484Q alone. These data demonstrate reduced sensitivity to vaccine elicited neutralising antibodies by L452R and E484Q but lack of synergistic loss of sensitivity. -
Natto extract, a Japanese fermented soybean food, directly inhibits viral infections including SARS-CoV-2 in vitro. 査読あり
Oba M, Rongduo W, Saito A, Okabayashi T, Yokota T, Yasuoka J, Sato Y, Nishifuji K, Wake H, Nibu Y, Mizutani T
Biochemical and biophysical research communications 570 21 - 25 2021年7月
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Hiroko Inagaki, Akatsuki Saito, Chiho Kaneko, Hironobu Sugiyama, Tamaki Okabayashi, Shouichi Fujimoto
Pathogens 10 ( 6 ) 754 - 754 2021年6月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：MDPI AG
More than 1 year has passed since social activities have been restricted due to the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). More recently, novel SARS-CoV-2 variants have been spreading around the world, and there is growing concern that they may have higher transmissibility and that the protective efficacy of vaccines may be weaker against them. Immediate measures are needed to reduce human exposure to the virus. In this study, the antiviral efficacy of deep-ultraviolet light-emitting diode (DUV-LED) irradiation (280 ± 5 nm, 3.75 mW/cm2) against three SARS-CoV-2 variants was evaluated. For the B.1.1.7, B.1.351, and P.1 variant strains, irradiation of the virus stocks for 1 s resulted in infectious titer reduction rates of 96.3%, 94.6%, and 91.9%, respectively, and with irradiation for 5 s, the rates increased to 99.9%, 99.9%, and 99.8%, respectively. We also tested the effect of pulsed DUV-LED irradiation (7.5 mW/cm2, duty rate: 50%, frequency: 1 kHz) under the same output conditions as for continuous irradiation and found that the antiviral efficacy of pulsed and continuous irradiation was the same. These findings suggest that by further developing and optimizing the DUV-LED device to increase its output, it may be possible to instantly inactivate SARS-CoV-2 with DUV-LED irradiation.
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SARS-CoV-2 spike L452R variant evades cellular immunity and increases infectivity 査読あり 国際誌
Chihiro Motozono, Mako Toyoda, Jiri Zahradnik, Akatsuki Saito, Hesham Nasser, Toong Seng Tan, Isaac Ngare, Izumi Kimura, Keiya Uriu, Yusuke Kosugi, Yuan Yue, Ryo Shimizu, Jumpei Ito, Shiho Torii, Akiko Yonekawa, Nobuyuki Shimono, Yoji Nagasaki, Rumi Minami, Takashi Toya, Noritaka Sekiya, Takasuke Fukuhara, Yoshiharu Matsuura, Gideon Schreiber, Terumasa Ikeda, So Nakagawa, Takamasa Ueno, Kei Sato
Cell Host & Microbe 29 ( 7 ) 1124 - 1136.e11 2021年6月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Elsevier BV
Many SARS-CoV-2 variants with naturally acquired mutations have emerged. These mutations can affect viral properties such as infectivity and immune resistance. Although the sensitivity of naturally occurring SARS-CoV-2 variants to humoral immunity has been investigated, sensitivity to human leukocyte antigen (HLA)-restricted cellular immunity remains largely unexplored. Here, we demonstrate that two recently emerging mutations in the receptor-binding domain of the SARS-CoV-2 spike protein, L452R (in B.1.427/429 and B.1.617) and Y453F (in B.1.1.298), confer escape from HLA-A24-restricted cellular immunity. These mutations reinforce affinity toward the host entry receptor ACE2. Notably, the L452R mutation increases spike stability, viral infectivity, viral fusogenicity, and thereby promotes viral replication. These data suggest that HLA-restricted cellular immunity potentially affects the evolution of viral phenotypes and that a further threat of the SARS-CoV-2 pandemic is escape from cellular immunity.
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Rapid Inactivation of SARS-CoV-2 with Ozonated Water 査読あり
Hiroko Inagaki, Akatsuki Saito, Putu Eka Sudaryatma, Hironobu Sugiyama, Tamaki Okabayashi, Shouichi Fujimoto
Ozone: Science & Engineering 43 ( 3 ) 208 - 212 2021年5月
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Bovine respiratory coronavirus enhances bacterial adherence by upregulating expression of cellular receptors on bovine respiratory epithelial cells 査読あり
Watcharapong Fahkrajang, Putu Eka Sudaryatma, Hirohisa Mekata, Saori Hamabe, Akatsuki Saito, Tamaki Okabayashi
Veterinary Microbiology 255 109017 - 109017 2021年4月
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Yumi Kirino, Keita Ishijima, Miho Miura, Taro Nomachi, Eugene Mazimpaka, Putu Eka Sudaryatma, Atsushi Yamanaka, Ken Maeda, Takayuki Sugimoto, Akatsuki Saito, Hirohisa Mekata, Tamaki Okabayashi
Viruses 13 ( 2 ) 229 - 229 2021年2月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：MDPI AG
Severe fever with thrombocytopenia syndrome virus (SFTSV) is the causative agent of SFTS, an emerging tick-borne disease in East Asia, and is maintained in enzootic cycles involving ticks and a range of wild animal hosts. Direct transmission of SFTSV from cats and dogs to humans has been identified in Japan, suggesting that veterinarians and veterinary nurses involved in small-animal practice are at occupational risk of SFTSV infection. To characterize this risk, we performed a sero-epidemiological survey in small-animal-practice workers and healthy blood donors in Miyazaki prefecture, which is the prefecture with the highest per capita number of recorded cases of SFTS in Japan. Three small-animal-practice workers were identified as seropositive by ELISA, but one had a negative neutralization-test result and so was finally determined to be seronegative, giving a seropositive rate of 2.2% (2 of 90), which was significantly higher than that in healthy blood donors (0%, 0 of 1000; p < 0.05). The seroprevalence identified here in small-animal-practice workers was slightly higher than that previously reported in other high-risk workers engaged in agriculture and forestry in Japan. Thus, enhancement of small-animal-practice workers’ awareness of biosafety at animal hospitals is necessary for control of SFTSV.
DOI： 10.3390/v13020229
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Saori Matsuoka, Takeo Kuwata, Hiroshi Ishii, Tsuyoshi Sekizuka, Makoto Kuroda, Masato Sano, Midori Okazaki, Hiroyuki Yamamoto, Mikiko Shimizu, Shuzo Matsushita, Yohei Seki, Akatsuki Saito, Hiromi Sakawaki, Vanessa M. Hirsch, Tomoyuki Miura, Hirofumi Akari, Tetsuro Matano
Journal of Virology 95 ( 7 ) 2021年1月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：American Society for Microbiology
<title>ABSTRACT</title>
Virus infection induces B cells with a wide variety of B-cell receptor (BCR) repertoires. Patterns of induced BCR repertoires are different in individuals, while the underlying mechanism causing this difference remains largely unclear. In particular, the impact of germ line BCR immunoglobulin (Ig) gene polymorphism on B-cell/antibody induction has not fully been determined. In the present study, we found a potent antibody induction associated with a germ line BCR Ig gene polymorphism. B404 class antibodies, which were previously reported as potent anti-simian immunodeficiency virus (anti-SIV) neutralizing antibodies using the germ line VH3.33 gene-derived Ig heavy chain, were induced in 5 of 10 rhesus macaques after SIVsmH635FC infection. Investigation of VH3.33 genes in B404 class antibody inducers (<italic>n</italic> = 5) and noninducers (<italic>n</italic> = 5) revealed association of B404 class antibody induction with a germ line VH3.33 polymorphism. Analysis of reconstructed antibodies indicated that the VH3.33 residue 38 is the determinant for B404 class antibody induction. B404 class antibodies were induced in all the macaques possessing the B404-associated VH3.33 allele, even under undetectable viremia. Our results show that a single nucleotide polymorphism in germ line VH genes could be a determinant for induction of potent antibodies against virus infection, implying that germ line VH gene polymorphisms can be a factor restricting effective antibody induction or responsiveness to vaccination.
<bold>IMPORTANCE</bold> Vaccines against a wide variety of infectious diseases have been developed mostly to induce antibodies targeting pathogens. However, a small but significant percentage of people fail to mount potent antibody responses after vaccination, while the underlying mechanism of host failure in antibody induction remains largely unclear. In particular, the impact of germ line B-cell receptor (BCR)/antibody immunoglobulin (Ig) gene polymorphism on B-cell/antibody induction has not fully been determined. In the present study, we found a potent anti-simian immunodeficiency virus neutralizing antibody induction associated with a germ line BCR/antibody Ig gene polymorphism in rhesus macaques. Our results demonstrate that a single nucleotide polymorphism in germ line Ig genes could be a determinant for induction of potent antibodies against virus infection, implying that germ line BCR/antibody Ig gene polymorphisms can be a factor restricting effective antibody induction or responsiveness to vaccination.DOI： 10.1128/jvi.02455-20
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Rapid inactivation of SARS-CoV-2 with Deep-UV LED irradiation. 査読あり
Inagaki H, Saito A, Sugiyama H, Okabayashi T, Fujimoto S
Emerging microbes & infections 1 - 8 2020年7月
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Bovine Respiratory Syncytial Virus Decreased Pasteurella multocida Adherence by Downregulating the Expression of Intercellular Adhesion Molecule-1 on the Surface of Upper Respiratory Epithelial Cells. 査読あり 国際誌
Sudaryatma PE, Saito A, Mekata H, Kubo M, Fahkrajang W, Okabayashi T
Veterinary microbiology 246 108748 - 108748 2020年7月
記述言語：英語 掲載種別：研究論文（学術雑誌）
The synergistic infection of bovine respiratory syncytial virus (BRSV) and Pasteurella multocida (PM) may predispose cattle to develop severe pneumonia. Previously, we reported that BRSV infection significantly decreased PM adherence to the upper respiratory epithelial cells. It may allow bacteria to invade into the lower respiratory tract and lead to severe pneumonia. To investigate whether BRSV infection regulates the cell surface adherence receptor on bovine trachea epithelial cells (bTECs), we performed proteomic and functional analyses. BRSV infection decreased the expression of intercellular adhesion molecule-1 (ICAM1) on bTECs. Inhibition and knockdown experiments using anti-ICAM1 antibody and siRNAs targeting ICAM1 indicated that PM adherence to bTECs was dependent on ICAM1 expression. These data suggest that under normal conditions bTECs may capture PM in the upper respiratory tract, while BRSV infection reverses this mechanism. The proposed gateway function of bTECs is disrupted by BRSV infection that may facilitate bacterial invasion into the lower respiratory tract and lead to secondary or more severe respiratory infection.
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The 4th and 112th Residues of Viral Capsid Cooperatively Modulate Capsid-CPSF6 Interactions of HIV-1. 査読あり
Saito A, Sultana T, Ode H, Nohata K, Samune Y, Nakayama EE, Iwatani Y, Shioda T
AIDS research and human retroviruses 2020年2月
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Putu Eka Sudaryatma, Akatsuki Saito, Hirohisa Mekata, Meiko Kubo, Watcharapong Fahkrajang, Eugene Mazimpaka, Tamaki Okabayashi
Frontiers in microbiology 11 1676 - 1676 2020年
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Frontiers Media SA
Coinfection by bovine respiratory syncytial virus (BRSV) and Pasteurella multocida (PM) frequently has been observed in cattle that develop severe pneumonia. We recently reported that BRSV infection significantly increased PM adherence to bovine lower respiratory tract epithelial cells. However, the molecular mechanisms of enhanced PM adherence are not completely understood. To investigate whether BRSV infection regulates any cellular adherence receptors on bovine bronchus- and lung-epithelial cells, we performed proteomic and functional analyses. The proteomic analysis showed that BRSV infection increased the accumulation of the platelet-activating factor receptor (PAFR) in both cell types. Molecular experiments, including specific blockade, knockdown, and overexpression of PAFR, indicated that PM adherence to these cell types depended on PAFR expression. These findings highlight the role, in cattle with severe pneumonia, of the synergistic effect of coinfection by BRSV and PM in the lower respiratory tract.
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Evaluation of novel rapid detection kits for dengue virus NS1 antigen in Dhaka, Bangladesh, in 2017 査読あり
Suzuki K, Nakayama EE, Saito A, Egawa A, Sato T, Phadungsombat J, Rahim R, Hasan A, Iwamoto H, Rahman M, Shioda T
Virology Journal 2019年12月
記述言語：英語 掲載種別：研究論文（学術雑誌）
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Discovery of a small molecule inhibitor targeting dengue virus NS5 RNA-dependent RNA polymerase. 査読あり
Shimizu H, Saito A, Mikuni J, Nakayama EE, Koyama H, Honma T, Shirouzu M, Sekine SI, Shioda T
PLoS neglected tropical diseases 13 ( 11 ) e0007894 2019年11月
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Suzuki K, Phadungsombat J, Nakayama EE, Saito A, Egawa A, Sato T, Rahim R, Hasan A, Lin MY, Takasaki T, Rahman M, Shioda T
Infection, Genetics and Evolution 2019年11月
記述言語：英語 掲載種別：研究論文（学術雑誌）
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Multiple pathways to avoid IFN-β sensitivity of HIV-1 by mutations in capsid 査読あり
Sultana T, Mamede JI, Saito A, Ode H, Nohata K, Cohen R, Nakayama EE, Iwatani Y, Yamashita M, Hope TJ, Shioda T
Journal of Virology 93 ( 23 ) 2019年9月
記述言語：英語 掲載種別：研究論文（学術雑誌）
DOI： 10.1128/JVI.00986-19