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Article ; Online: Seroprevalence of SARS-CoV-2 antibodies in dogs and cats during the early and mid-pandemic periods in Japan

Seiya Yamayoshi / Mutsumi Ito / Kiyoko Iwatsuki-Horimoto / Atsuhiro Yasuhara / Moe Okuda / Taiki Hamabata / Jurika Murakami / Calvin Duong / Tsukasa Yamamoto / Yudai Kuroda / Ken Maeda / Yoshihiro Kawaoka

One Health, Vol 17, Iss , Pp 100588- (2023)

2023

Abstract: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has continued to circulate in humans since its emergence in 2019. While infection in humans continues, numerous spillover events to at least 32 animal species, including companion and zoo ... ...

Abstract	Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has continued to circulate in humans since its emergence in 2019. While infection in humans continues, numerous spillover events to at least 32 animal species, including companion and zoo animals, have been reported. Since dogs and cats are highly susceptible to SARS-CoV-2 and have direct contact with their owners and other household members, it is important to know the prevalence of SARS-CoV-2 in dogs and cats. Here, we established an ELISA to detect serum antibodies against the receptor-binding domain and the ectodomain of the SARS-CoV-2 spike and nucleocapsid proteins. Using this ELISA, we assessed seroprevalence in 488 dog serum samples and 355 cat serum samples that were collected during the early pandemic period (between May and June of 2020) and 312 dog serum samples and 251 cat serum samples that were collected during the mid-pandemic period (between October 2021 and January 2022). We found that two dog serum samples (0.41%) collected in 2020, one cat serum sample (0.28%) collected in 2020, and four cat serum samples (1.6%) collected in 2021 were positive for antibodies against SARS-CoV-2. No dog serum samples collected in 2021 were positive for these antibodies. We conclude that the seroprevalence of SARS-CoV-2 antibodies in dogs and cats in Japan is low, suggesting that these animals are not a major SARS-CoV-2 reservoir.
Keywords	SARS-CoV-2 ; Seroprevalence ; Dog ; Cat ; COVID-19 ; Medicine (General) ; R5-920
Subject code	630
Language	English
Publishing date	2023-12-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Airway surveillance and lung viral control by memory T cells induced by COVID-19 mRNA vaccine

Brock Kingstad-Bakke / Thomas Cleven / Hailey Bussan / Boyd L. Yount Jr. / Ryuta Uraki / Kiyoko Iwatsuki-Horimoto / Michiko Koga / Shinya Yamamoto / Hiroshi Yotsuyanagi / Hongtae Park / Jay S. Mishra / Sathish Kumar / Ralph S. Baric / Peter J. Halfmann / Yoshihiro Kawaoka / M. Suresh

JCI Insight, Vol 8, Iss

2023 Volume 22

Abstract: Although SARS-CoV-2 evolution seeds a continuous stream of antibody-evasive viral variants, COVID-19 mRNA vaccines provide robust protection against severe disease and hospitalization. Here, we asked whether mRNA vaccine–induced memory T cells limit lung ...

Abstract	Although SARS-CoV-2 evolution seeds a continuous stream of antibody-evasive viral variants, COVID-19 mRNA vaccines provide robust protection against severe disease and hospitalization. Here, we asked whether mRNA vaccine–induced memory T cells limit lung SARS-CoV-2 replication and severe disease. We show that mice and humans receiving booster BioNTech mRNA vaccine developed potent CD8 T cell responses and showed similar kinetics of expansion and contraction of granzyme B/perforin-expressing effector CD8 T cells. Both monovalent and bivalent mRNA vaccines elicited strong expansion of a heterogeneous pool of terminal effectors and memory precursor effector CD8 T cells in spleen, inguinal and mediastinal lymph nodes, pulmonary vasculature, and most surprisingly in the airways, suggestive of systemic and regional surveillance. Furthermore, we document that: (a) CD8 T cell memory persists in multiple tissues for > 200 days; (b) following challenge with pathogenic SARS-CoV-2, circulating memory CD8 T cells rapidly extravasate to the lungs and promote expeditious viral clearance, by mechanisms that require CD4 T cell help; and (c) adoptively transferred splenic memory CD8 T cells traffic to the airways and promote lung SARS-CoV-2 clearance. These findings provide insights into the critical role of memory T cells in preventing severe lung disease following breakthrough infections with antibody-evasive SARS-CoV-2 variants.
Keywords	COVID-19 ; Immunology ; Medicine ; R
Subject code	610
Language	English
Publishing date	2023-11-01T00:00:00Z
Publisher	American Society for Clinical investigation
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Characterization of a SARS-CoV-2 EG.5.1 clinical isolate in vitro and in vivo

Cell Reports, Vol 42, Iss 12, Pp 113580- (2023)

2023

Abstract: Summary: EG.5.1 is a subvariant of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron XBB variant that is rapidly increasing in prevalence worldwide. However, the pathogenicity, transmissibility, and immune evasion properties of ... ...

Abstract	Summary: EG.5.1 is a subvariant of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron XBB variant that is rapidly increasing in prevalence worldwide. However, the pathogenicity, transmissibility, and immune evasion properties of isolates of EG.5.1 are largely unknown. Here, we show that there are no obvious differences in growth ability and pathogenicity between EG.5.1 and XBB.1.5 in hamsters. We also demonstrate that, like XBB.1.5, EG.5.1 is transmitted more efficiently between hamsters compared to its predecessor, BA.2. In contrast, unlike XBB.1.5, we detect EG.5.1 in the lungs of four of six exposed hamsters, suggesting that the virus properties of EG.5.1 are different from those of XBB.1.5. Finally, we find that the neutralizing activity of plasma from convalescent individuals against EG.5.1 was slightly, but significantly, lower than that against XBB.1.5 or XBB.1.9.2. Our data suggest that the different virus properties after transmission and the altered antigenicity of EG.5.1 may be driving its increasing prevalence over XBB.1.5 in humans.
Keywords	CP: Microbiology ; CP: Immunology ; Biology (General) ; QH301-705.5
Language	English
Publishing date	2023-12-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Differences among epitopes recognized by neutralizing antibodies induced by SARS-CoV-2 infection or COVID-19 vaccination

Shinya Yamamoto / Seiya Yamayoshi / Mutsumi Ito / Yuko Sakai-Tagawa / Ichiro Nakachi / Rie Baba / Shigenobu Kamimoto / Takayuki Ogura / Shigehiro Hagiwara / Hideaki Kato / Hideaki Nakajima / Yoshifumi Uwamino / Kazuma Yagi / Norio Sugaya / Hiroyuki Nagai / Makoto Saito / Eisuke Adachi / Michiko Koga / Takeya Tsutsumi /

Calvin Duong / Moe Okuda / Jurika Murakami / Yuri Furusawa / Michiko Ujie / Kiyoko Iwatsuki-Horimoto / Hiroshi Yotsuyanagi / Yoshihiro Kawaoka

iScience, Vol 26, Iss 7, Pp 107208- (2023)

2023

Abstract: Summary: SARS-CoV-2 has gradually acquired amino acid substitutions in its S protein that reduce the potency of neutralizing antibodies, leading to decreased vaccine efficacy. Here, we attempted to obtain mutant viruses by passaging SARS-CoV-2 in the ... ...

Abstract	Summary: SARS-CoV-2 has gradually acquired amino acid substitutions in its S protein that reduce the potency of neutralizing antibodies, leading to decreased vaccine efficacy. Here, we attempted to obtain mutant viruses by passaging SARS-CoV-2 in the presence of plasma samples from convalescent patients or vaccinees to determine which amino acid substitutions affect the antigenicity of SARS-CoV-2. Several amino acid substitutions in the S2 region, as well as the N-terminal domain (NTD) and receptor-binding domain (RBD), affected the neutralization potency of plasma samples collected from vaccinees, indicating that amino acid substitutions in the S2 region as well as those in the NTD and RBD affect neutralization by vaccine-induced antibodies. Furthermore, the neutralizing potency of vaccinee plasma samples against mutant viruses we obtained or circulating viruses differed among individuals. These findings suggest that genetic backgrounds of vaccinees influence the recognition of neutralizing epitopes.
Keywords	Immunology ; Virology ; Science ; Q
Language	English
Publishing date	2023-07-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: The Anticoagulant Nafamostat Potently Inhibits SARS-CoV-2 S Protein-Mediated Fusion in a Cell Fusion Assay System and Viral Infection In Vitro in a Cell-Type-Dependent Manner

Mizuki Yamamoto / Maki Kiso / Yuko Sakai-Tagawa / Kiyoko Iwatsuki-Horimoto / Masaki Imai / Makoto Takeda / Noriko Kinoshita / Norio Ohmagari / Jin Gohda / Kentaro Semba / Zene Matsuda / Yasushi Kawaguchi / Yoshihiro Kawaoka / Jun-ichiro Inoue

Viruses, Vol 12, Iss 629, p

2020 Volume 629

Abstract: Although infection by SARS-CoV-2, the causative agent of coronavirus pneumonia disease (COVID-19), is spreading rapidly worldwide, no drug has been shown to be sufficiently effective for treating COVID-19. We previously found that nafamostat mesylate, an ...

Abstract	Although infection by SARS-CoV-2, the causative agent of coronavirus pneumonia disease (COVID-19), is spreading rapidly worldwide, no drug has been shown to be sufficiently effective for treating COVID-19. We previously found that nafamostat mesylate, an existing drug used for disseminated intravascular coagulation (DIC), effectively blocked Middle East respiratory syndrome coronavirus (MERS-CoV) S protein-mediated cell fusion by targeting transmembrane serine protease 2 (TMPRSS2), and inhibited MERS-CoV infection of human lung epithelium-derived Calu-3 cells. Here we established a quantitative fusion assay dependent on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) S protein, angiotensin I converting enzyme 2 (ACE2) and TMPRSS2, and found that nafamostat mesylate potently inhibited the fusion while camostat mesylate was about 10-fold less active. Furthermore, nafamostat mesylate blocked SARS-CoV-2 infection of Calu-3 cells with an effective concentration (EC) 50 around 10 nM, which is below its average blood concentration after intravenous administration through continuous infusion. On the other hand, a significantly higher dose (EC 50 around 30 mM) was required for VeroE6/TMPRSS2 cells, where the TMPRSS2-independent but cathepsin-dependent endosomal infection pathway likely predominates. Together, our study shows that nafamostat mesylate potently inhibits SARS-CoV-2 S protein-mediated fusion in a cell fusion assay system and also inhibits SARS-CoV-2 infection in vitro in a cell-type-dependent manner. These findings, together with accumulated clinical data regarding nafamostat’s safety, make it a likely candidate drug to treat COVID-19.
Keywords	SARS-CoV-2 ; TMPRSS2 ; fusion inhibitor ; Microbiology ; QR1-502 ; covid19
Language	English
Publishing date	2020-06-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Book ; Online: The Anticoagulant Nafamostat Potently Inhibits SARS-CoV-2 S Protein-Mediated Fusion in a Cell Fusion Assay System and Viral Infection In Vitro in a Cell-Type-Dependent Manner

Viruses ; Volume 12 ; Issue 6

2020

Abstract	Although infection by SARS-CoV-2, the causative agent of coronavirus pneumonia disease (COVID-19), is spreading rapidly worldwide, no drug has been shown to be sufficiently effective for treating COVID-19. We previously found that nafamostat mesylate, an existing drug used for disseminated intravascular coagulation (DIC), effectively blocked Middle East respiratory syndrome coronavirus (MERS-CoV) S protein-mediated cell fusion by targeting transmembrane serine protease 2 (TMPRSS2), and inhibited MERS-CoV infection of human lung epithelium-derived Calu-3 cells. Here we established a quantitative fusion assay dependent on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) S protein, angiotensin I converting enzyme 2 (ACE2) and TMPRSS2, and found that nafamostat mesylate potently inhibited the fusion while camostat mesylate was about 10-fold less active. Furthermore, nafamostat mesylate blocked SARS-CoV-2 infection of Calu-3 cells with an effective concentration (EC)50 around 10 nM, which is below its average blood concentration after intravenous administration through continuous infusion. On the other hand, a significantly higher dose (EC50 around 30 mM) was required for VeroE6/TMPRSS2 cells, where the TMPRSS2-independent but cathepsin-dependent endosomal infection pathway likely predominates. Together, our study shows that nafamostat mesylate potently inhibits SARS-CoV-2 S protein-mediated fusion in a cell fusion assay system and also inhibits SARS-CoV-2 infection in vitro in a cell-type-dependent manner. These findings, together with accumulated clinical data regarding nafamostat’ s safety, make it a likely candidate drug to treat COVID-19.
Keywords	SARS-CoV-2 ; TMPRSS2 ; fusion inhibitor ; covid19
Language	English
Publishing date	2020-06-10
Publisher	Multidisciplinary Digital Publishing Institute
Publishing country	ch
Document type	Book ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Characterization of SARS-CoV-2 Omicron BA.2.75 clinical isolates

Ryuta Uraki / Shun Iida / Peter J. Halfmann / Seiya Yamayoshi / Yuichiro Hirata / Kiyoko Iwatsuki-Horimoto / Maki Kiso / Mutsumi Ito / Yuri Furusawa / Hiroshi Ueki / Yuko Sakai-Tagawa / Makoto Kuroda / Tadashi Maemura / Taksoo Kim / Sohtaro Mine / Noriko Iwamoto / Rong Li / Yanan Liu / Deanna Larson /

Shuetsu Fukushi / Shinji Watanabe / Ken Maeda / Zhongde Wang / Norio Ohmagari / James Theiler / Will Fischer / Bette Korber / Masaki Imai / Tadaki Suzuki / Yoshihiro Kawaoka

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

2023 Volume 11

Abstract: Omicron subvariants may differ in their replicative fitness and their potential to cause more severe disease. In this study, the authors characterized Omicron BA.2.75 in a hamster model and found that it replicates more efficiently in the lungs than BA.2 ...

Abstract	Omicron subvariants may differ in their replicative fitness and their potential to cause more severe disease. In this study, the authors characterized Omicron BA.2.75 in a hamster model and found that it replicates more efficiently in the lungs than BA.2 and BA.5.
Keywords	Science ; Q
Language	English
Publishing date	2023-03-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Experimental infection of Cynomolgus Macaques with highly pathogenic H5N1 influenza virus through the aerosol route

Tokiko Watanabe / Kiyoko Iwatsuki-Horimoto / Maki Kiso / Noriko Nakajima / Kenta Takahashi / Tiago Jose da Silva Lopes / Mutsumi Ito / Satoshi Fukuyama / Hideki Hasegawa / Yoshihiro Kawaoka

Scientific Reports, Vol 8, Iss 1, Pp 1-

2018 Volume 8

Abstract: Abstract Several animal models are used to study influenza viruses. Intranasal inoculation of animals with a liquid inoculum is one of the main methods used to experimentally infect animals with influenza virus; however, this method does not reflect the ... ...

Abstract	Abstract Several animal models are used to study influenza viruses. Intranasal inoculation of animals with a liquid inoculum is one of the main methods used to experimentally infect animals with influenza virus; however, this method does not reflect the natural infection with influenza virus by contact or aerosol route. Aerosol inhalation methods have been established with several influenza viruses for mouse and ferret models, but few studies have evaluated inoculation routes in a nonhuman primates (NHP) model. Here, we performed the experimental infection of NHPs with a highly pathogenic H5N1 influenza virus via the aerosol route and demonstrated that aerosol infection had no effect on clinical outcome, but caused broader infection throughout all of the lobes of the lung compared with a non-aerosolized approach. Aerosol infection therefore represents an option for inoculation of NHPs in future studies.
Keywords	Medicine ; R ; Science ; Q
Language	English
Publishing date	2018-03-01T00:00:00Z
Publisher	Nature Publishing Group
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Diversity of antigenic mutants of influenza A(H1N1)pdm09 virus escaped from human monoclonal antibodies

Atsuhiro Yasuhara / Seiya Yamayoshi / Priyanka Soni / Toru Takenaga / Chiharu Kawakami / Emi Takashita / Yuko Sakai-Tagawa / Ryuta Uraki / Mutsumi Ito / Kiyoko Iwatsuki-Horimoto / Tadahiro Sasaki / Kazuyoshi Ikuta / Shinya Yamada / Yoshihiro Kawaoka

Scientific Reports, Vol 7, Iss 1, Pp 1-

2017 Volume 9

Abstract: Abstract Since the 2017 Southern Hemisphere influenza season, the A(H1N1)pdm09-like virus recommended for use in the vaccine was changed because human, but not ferret, sera distinguish A(H1N1)pdm09 viruses isolated after 2013 from the previously ... ...

Abstract	Abstract Since the 2017 Southern Hemisphere influenza season, the A(H1N1)pdm09-like virus recommended for use in the vaccine was changed because human, but not ferret, sera distinguish A(H1N1)pdm09 viruses isolated after 2013 from the previously circulating strains. An amino acid substitution, lysine to glutamine, at position 166 (H3 numbering) in the major antigenic site of HA was reported to be responsible for the antigenic drift. Here, we obtained two anti-A(H1N1)pdm09 HA monoclonal antibodies that failed to neutralize viruses isolated after 2013 from a vaccinated volunteer. Escape mutations were identified at position 129, 165, or 166 in the major antigenic site of HA. Competitive growth of the escape mutant viruses with the wild-type virus revealed that some escape mutants possessing an amino acid substitution other than K166Q showed superior growth to that of the wild-type virus. These results suggest that in addition to the K166Q mutation that occurred in epidemic strains, other HA mutations can confer resistance to antibodies that recognize the K166 area, leading to emergence of epidemic strains with such mutations.
Keywords	Medicine ; R ; Science ; Q
Subject code	570
Language	English
Publishing date	2017-12-01T00:00:00Z
Publisher	Nature Publishing Group
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Multi-omics of NET formation and correlations with CNDP1, PSPB, and L-cystine levels in severe and mild COVID-19 infections

Lisa M. Bramer / Robert D. Hontz / Amie J. Eisfeld / Amy C. Sims / Young-Mo Kim / Kelly G. Stratton / Carrie D. Nicora / Marina A. Gritsenko / Athena A. Schepmoes / Osamu Akasaka / Michiko Koga / Takeya Tsutsumi / Morio Nakamura / Ichiro Nakachi / Rie Baba / Hiroki Tateno / Shoji Suzuki / Hideaki Nakajima / Hideaki Kato /

Kazunari Ishida / Makoto Ishii / Yoshifumi Uwamino / Keiko Mitamura / Vanessa L. Paurus / Ernesto S. Nakayasu / Isaac K. Attah / Andrew G. Letizia / Katrina M. Waters / Thomas O. Metz / Karen Corson / Yoshihiro Kawaoka / Vincent R. Gerbasi / Hiroshi Yotsuyanagi / Kiyoko Iwatsuki-Horimoto

Heliyon, Vol 9, Iss 3, Pp e13795- (2023)

2023

Abstract: The detailed mechanisms of COVID-19 infection pathology remain poorly understood. To improve our understanding of SARS-CoV-2 pathology, we performed a multi-omics and correlative analysis of an immunologically naïve SARS-CoV-2 clinical cohort from blood ... ...

Abstract	The detailed mechanisms of COVID-19 infection pathology remain poorly understood. To improve our understanding of SARS-CoV-2 pathology, we performed a multi-omics and correlative analysis of an immunologically naïve SARS-CoV-2 clinical cohort from blood plasma of uninfected controls, mild, and severe infections. Consistent with previous observations, severe patient populations showed an elevation of pulmonary surfactant levels. Intriguingly, mild patients showed a statistically significant elevation in the carnosine dipeptidase modifying enzyme (CNDP1). Mild and severe patient populations showed a strong elevation in the metabolite L-cystine (oxidized form of the amino acid cysteine) and enzymes with roles in glutathione metabolism. Neutrophil extracellular traps (NETs) were observed in both mild and severe populations, and NET formation was higher in severe vs. mild samples. Our correlative analysis suggests a potential protective role for CNDP1 in suppressing PSPB release from the pulmonary space whereas NET formation correlates with increased PSPB levels and disease severity. In our discussion we put forward a possible model where NET formation drives pulmonary occlusions and CNDP1 promotes antioxidation, pleiotropic immune responses, and vasodilation by accelerating histamine synthesis.
Keywords	CNDP1 ; Carnosinase ; COVID-19 ; SARS-CoV-2 ; NETs ; ROS ; Science (General) ; Q1-390 ; Social sciences (General) ; H1-99
Subject code	572
Language	English
Publishing date	2023-03-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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