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Article ; Online: Antiviral Agents against Omicron Subvariant BA.4.6 In Vitro. Reply.

Uraki, Ryuta / Imai, Masaki / Kawaoka, Yoshihiro

2023 Volume 388, Issue 5, Page(s) e12

MeSH term(s)	Humans ; Antiviral Agents/therapeutic use
Chemical Substances	Antiviral Agents
Language	English
Publishing date	2023-02-01
Publishing country	United States
Document type	Letter ; Comment
ZDB-ID	207154-x
ISSN	1533-4406 ; 0028-4793
ISSN (online)	1533-4406
ISSN	0028-4793
DOI	10.1056/NEJMc2216611
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Article ; Online: Temperature-variable apparatus for measuring Barnett field.

Umeda, Maki / Chudo, Hiroyuki / Imai, Masaki / Sato, Nana / Saitoh, Eiji

The Review of scientific instruments

2023 Volume 94, Issue 6

Abstract: We have developed experimental equipment for observing the Barnett effect, in which mechanical rotation magnetizes an object, at low temperatures. A sample in a rotor is rotated bidirectionally using a temperature-controlled high-pressure gas. The stray ... ...

Abstract	We have developed experimental equipment for observing the Barnett effect, in which mechanical rotation magnetizes an object, at low temperatures. A sample in a rotor is rotated bidirectionally using a temperature-controlled high-pressure gas. The stray field generated from the sample due to the Barnett effect was detected using a fluxgate magnetic sensor with a sensitivity on the order of several picoteslas, even at low temperatures. By replacing the rotor with a solenoid coil, the magnetic susceptibility of the sample was estimated from the stray field to be of the same order of magnitude as that due to the Barnett effect. The Barnett field was estimated using the dipole model. To assess the performance of the setup at low temperatures, measurements were performed on commercial magnetite (Fe3O4) nanogranules. We confirmed the accordance of the g' factor between the experimental results using the present setup and those of our previous study performed at room temperature.
Language	English
Publishing date	2023-10-20
Publishing country	United States
Document type	Journal Article
ZDB-ID	209865-9
ISSN	1089-7623 ; 0034-6748
ISSN (online)	1089-7623
ISSN	0034-6748
DOI	10.1063/5.0142318
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Article ; Online: A novel rhabdovirus detected in Anisakis larvae distributed in the coastal areas of Japan: Viral genome analysis and possible coevolutionary relationship between virus and host nematodes.

Sugimoto, Kana / Kobayashi, Daisuke / Ohshima, Shigeru / Imai, Masaki / Ohta, Nobuo

Parasitology international

2023 Volume 99, Page(s) 102834

Abstract: In the last decade, it has become evident that various RNA viruses infect helminths including Order Ascaridida. However, there is still no information available for viruses infecting Anisakis. We herewith demonstrate the presence of a novel rhabdovirus ... ...

Abstract	In the last decade, it has become evident that various RNA viruses infect helminths including Order Ascaridida. However, there is still no information available for viruses infecting Anisakis. We herewith demonstrate the presence of a novel rhabdovirus from Anisakis larvae detected by next-generation sequencing analysis and following RT-PCR. We determined the nearly all nucleotide sequence (12,376 nucleotides) of the viral genome composed of seven open reading frames, and we designated the virus as Suzukana rhabdo-like virus (SkRV). BLASTx search indicated that SkRV is a novel virus belonging to the subfamily Betanemrhavirus, rhabdovirus infecting parasitic nematodes of the Order Ascaridida. SkRV sequence was detectable only in the total RNA but not in the genomic DNA of Anisakis, ruling out the possibility of SkRV being an endogenous viral element incorporated into the host genomic DNA. When we individually tested Anisakis larvae obtained from Scomber japonicus migrating in the coastal waters of Japan, not all but around 40% were SkRV-positive. In the phylogenetic trees of Betanemrhavirus and of the host Ascaridida nematodes, we observed that evolutional distances of viruses were, to some extent, parallel with that of host nematodes, suggesting that viral evolution could have been correlated with evolution of the host. Although biological significance of SkRV on Anisakis larvae is still remained unknown, it is interesting if SkRV were somehow related to the pathogenesis of anisakiasis, because it is important matter of public health in Japan and European countries consuming raw marine fishes.
MeSH term(s)	Animals ; Anisakis/genetics ; Larva/genetics ; Rhabdoviridae/genetics ; Japan/epidemiology ; Phylogeny ; Anisakiasis/parasitology ; Fishes/parasitology ; DNA ; Fish Diseases/epidemiology ; Fish Diseases/parasitology
Chemical Substances	DNA (9007-49-2)
Language	English
Publishing date	2023-12-04
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	1363151-2
ISSN	1873-0329 ; 1383-5769
ISSN (online)	1873-0329
ISSN	1383-5769
DOI	10.1016/j.parint.2023.102834
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Article ; Online: Receptor-Binding Specificity of Influenza Viruses.

Imai, Masaki / Takada, Kosuke / Kawaoka, Yoshihiro

Methods in molecular biology (Clifton, N.J.)

2022 Volume 2556, Page(s) 79–96

Abstract: Influenza A virus infection begins with the attachment of virus particles to sialic acid-containing receptors on the surface of host cells. This attachment is mediated by the viral surface glycoprotein hemagglutinin (HA). Influenza A viruses have a wide ... ...

Abstract	Influenza A virus infection begins with the attachment of virus particles to sialic acid-containing receptors on the surface of host cells. This attachment is mediated by the viral surface glycoprotein hemagglutinin (HA). Influenza A viruses have a wide host range, meaning they are able to infect many mammal and bird species. Influenza pandemics have been caused by viruses that contain genes from avian influenza viruses. Therefore, the infection of humans with avian influenza viruses, including avian H5Nx and H7Nx viruses, poses a huge threat to public health. These avian influenza viruses can transmit directly to humans from infected poultry, but do not spread easily among people, in part, due to differences in the receptor-binding specificities of human and avian influenza viruses. Therefore, conversion from avian- to human-type receptor-binding specificity is widely believed to be necessary for the efficient transmission of avian influenza viruses among humans. Accordingly, constant monitoring of the receptor-binding specificity of avian influenza viruses is important. In this chapter, we describe the protocol for assessing the receptor-binding specificity of influenza A viruses.
MeSH term(s)	Animals ; Hemagglutinins ; Hemagglutinins, Viral ; Humans ; Influenza A virus ; Influenza, Human ; Mammals ; Membrane Glycoproteins ; N-Acetylneuraminic Acid
Chemical Substances	Hemagglutinins ; Hemagglutinins, Viral ; Membrane Glycoproteins ; N-Acetylneuraminic Acid (GZP2782OP0)
Language	English
Publishing date	2022-09-29
Publishing country	United States
Document type	Journal Article
ISSN	1940-6029
ISSN (online)	1940-6029
DOI	10.1007/978-1-0716-2635-1_8
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Article ; Online: Development of a Mouse-Adapted Reporter SARS-CoV-2 as a Tool for Two-Photon In Vivo Imaging.

Ueki, Hiroshi / Kiso, Maki / Furusawa, Yuri / Iida, Shun / Yamayoshi, Seiya / Nakajima, Noriko / Imai, Masaki / Suzuki, Tadaki / Kawaoka, Yoshihiro

Viruses

2024 Volume 16, Issue 4

Abstract: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) often causes severe viral pneumonia. Although many studies using mouse models have examined the pathogenicity of SARS-CoV-2, COVID-19 pathogenesis remains poorly understood. In vivo imaging ... ...

Abstract	Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) often causes severe viral pneumonia. Although many studies using mouse models have examined the pathogenicity of SARS-CoV-2, COVID-19 pathogenesis remains poorly understood. In vivo imaging analysis using two-photon excitation microscopy (TPEM) is useful for elucidating the pathology of COVID-19, providing pathological insights that are not available from conventional histological analysis. However, there is no reporter SARS-CoV-2 that demonstrates pathogenicity in C57BL/6 mice and emits sufficient light intensity for two-photon in vivo imaging. Here, we generated a mouse-adapted strain of SARS-CoV-2 (named MASCV2-p25) and demonstrated its efficient replication in the lungs of C57BL/6 mice, causing fatal pneumonia. Histopathologic analysis revealed the severe inflammation and infiltration of immune cells in the lungs of MASCV2-p25-infected C57BL/6 mice, not unlike that observed in COVID-19 patients with severe pneumonia. Subsequently, we generated a mouse-adapted reporter SARS-CoV-2 (named MASCV-Venus-p9) by inserting the fluorescent protein-encoding gene Venus into MASCV2-p25 and sequential lung-to-lung passages in C57BL/6 mice. C57BL/6 mice infected with MASCV2-Venus-p9 exhibited severe pneumonia. In addition, the TPEM of the lungs of the infected C57BL/6J mice showed that the infected cells emitted sufficient levels of fluorescence for easy observation. These findings suggest that MASCV2-Venus-p9 will be useful for two-photon in vivo imaging studies of the pathogenesis of severe COVID-19 pneumonia.
MeSH term(s)	Animals ; Mice ; SARS-CoV-2/genetics ; SARS-CoV-2/pathogenicity ; SARS-CoV-2/physiology ; COVID-19/virology ; Mice, Inbred C57BL ; Lung/virology ; Lung/pathology ; Lung/diagnostic imaging ; Disease Models, Animal ; Humans ; Genes, Reporter ; Virus Replication
Language	English
Publishing date	2024-03-29
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2516098-9
ISSN	1999-4915 ; 1999-4915
ISSN (online)	1999-4915
ISSN	1999-4915
DOI	10.3390/v16040537
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Article ; Online: In vitro and in vivo characterization of SARS-CoV-2 strains resistant to nirmatrelvir.

Kiso, Maki / Furusawa, Yuri / Uraki, Ryuta / Imai, Masaki / Yamayoshi, Seiya / Kawaoka, Yoshihiro

Nature communications

2023 Volume 14, Issue 1, Page(s) 3952

Abstract: Nirmatrelvir, an oral antiviral agent that targets a SARS-CoV-2 main protease (3CLpro), is clinically useful against infection with SARS-CoV-2 including its omicron variants. Since most omicron subvariants have reduced sensitivity to many monoclonal ... ...

Abstract	Nirmatrelvir, an oral antiviral agent that targets a SARS-CoV-2 main protease (3CLpro), is clinically useful against infection with SARS-CoV-2 including its omicron variants. Since most omicron subvariants have reduced sensitivity to many monoclonal antibody therapies, potential SARS-CoV-2 resistance to nirmatrelvir is a major public health concern. Several amino acid substitutions have been identified as being responsible for reduced susceptibility to nirmatrelvir. Among them, we selected L50F/E166V and L50F/E166A/L167F in the 3CLpro because these combinations of substitutions are unlikely to affect virus fitness. We prepared and characterized delta variants possessing Nsp5-L50F/E166V and Nsp5-L50F/E166A/L167F. Both mutant viruses showed decreased susceptibility to nirmatrelvir and their growth in VeroE6/TMPRSS2 cells was delayed. Both mutant viruses showed attenuated phenotypes in a male hamster infection model, maintained airborne transmissibility, and were outcompeted by wild-type virus in co-infection experiments in the absence of nirmatrelvir, but less so in the presence of the drug. These results suggest that viruses possessing Nsp5-L50F/E166V and Nsp5-L50F/E166A/L167F do not become dominant in nature. However, it is important to closely monitor the emergence of nirmatrelvir-resistant SARS-CoV-2 variants because resistant viruses with additional compensatory mutations could emerge, outcompete the wild-type virus, and become dominant.
MeSH term(s)	Male ; Animals ; Cricetinae ; COVID-19 ; SARS-CoV-2/genetics ; Amino Acid Substitution ; Antiviral Agents/pharmacology ; Lactams ; Leucine ; Nitriles
Chemical Substances	Antiviral Agents ; Lactams ; Leucine (GMW67QNF9C) ; Nitriles
Language	English
Publishing date	2023-07-04
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/s41467-023-39704-x
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Article ; Online: Cardiomyopathy Does Not Exacerbate the Severity of Pneumonia Caused by a SARS-CoV-2 Delta Variant in the J2N-k Hamster Model.

Iwatsuki-Horimoto, Kiyoko / Ito, Mutsumi / Okuda-Hamabata, Moe / Takagi, Hisayoshi / Imai, Masaki / Kawaoka, Yoshihiro

Viruses

2023 Volume 15, Issue 12

Abstract: Cardiovascular disease is one of many risk factors that have been linked to increased severity or mortality in coronavirus disease 2019 (COVID-19) patients; however, the exact role of SARS-CoV-2 in the pathogenesis of cardiac inflammatory injury has not ... ...

Abstract	Cardiovascular disease is one of many risk factors that have been linked to increased severity or mortality in coronavirus disease 2019 (COVID-19) patients; however, the exact role of SARS-CoV-2 in the pathogenesis of cardiac inflammatory injury has not been established. A previous study reported that SARS-CoV-2 causes more severe disease with cardiomyopathy in a J2N-k animal model. Here, we investigated the sensitivity of J2N-k hamsters, as a cardiomyopathy animal model, to a delta strain of SARS-CoV-2 compared to J2N-n control animals. We found that J2N-k hamsters were less susceptible to this delta strain than J2N-n animals, and we found no evidence that cardiomyopathy is a risk factor in this animal model. Since the previous study reported that SARS-CoV-2 causes more severe disease with cardiomyopathy in the same animal model, further analysis of the relationship between cardiomyopathy and SARS-CoV-2 infection is needed.
MeSH term(s)	Humans ; Cricetinae ; Animals ; SARS-CoV-2 ; COVID-19/complications ; Cardiomyopathies/etiology ; Disease Models, Animal ; Mesocricetus
Language	English
Publishing date	2023-11-21
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2516098-9
ISSN	1999-4915 ; 1999-4915
ISSN (online)	1999-4915
ISSN	1999-4915
DOI	10.3390/v15122280
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Article: Expression of a Crry/p65 is reduced in acute lung injury induced by extracellular histones

Nagano, Fumihiko / Mizuno, Tomohiro / Imai, Masaki / Takahashi, Kazuo / Tsuboi, Naotake / Maruyama, Shoichi / Mizuno, Masashi

FEBS Open Bio. 2022 Jan., v. 12, no. 1

2022

Abstract: Acute lung injury (ALI) occurs in patients with severe sepsis and has a mortality rate of 40%–60%. Severe sepsis promotes the release of histones from dying cells, which can induce platelet aggregation, activate coagulation and cause endothelial cell (EC) ...

Abstract	Acute lung injury (ALI) occurs in patients with severe sepsis and has a mortality rate of 40%–60%. Severe sepsis promotes the release of histones from dying cells, which can induce platelet aggregation, activate coagulation and cause endothelial cell (EC) death. We previously reported that the expression of membrane complement receptor type 1‐related gene Y (Crry)/p65, which plays a principal role in defence against abnormal activation of complement in the blood, is reduced in response to peritoneal mesothelial cell injury, and we hence hypothesized that a similar mechanism occurs in pulmonary ECs. In this study, we examined the role of Crry/p65 in histone‐mediated ALI using an experimental animal model. In ALI model mice, exposure to extracellular histones induces lung injury and results in a decrease in Crry/p65 expression. The levels of lactic acid dehydrogenase (LDH), a marker of cell damage, were significantly increased in the serum of ALI model compared with vehicle mice. The significant inverse correlation between the expression of Crry/p65 and LDH levels in plasma revealed an association between Crry/p65 expression and cell damage. The levels of complement component 3a (C3a) were also significantly increased in the serum of the ALI model compared with vehicle mice. Notably, a C3a receptor antagonist ameliorated lung injury induced by histones. We hypothesize that extracellular histones induce complement activation via down‐regulation of Crry/p65 and that C3a might serve as a therapeutic target for the treatment of ALI.
Keywords	animal models ; antagonists ; blood serum ; coagulation ; complement ; death ; endothelial cells ; genes ; histones ; laboratory animals ; lactate dehydrogenase ; lungs ; mortality ; platelet aggregation ; therapeutics
Language	English
Dates of publication	2022-01
Size	p. 192-202.
Publishing place	John Wiley & Sons, Ltd
Document type	Article
Note	JOURNAL ARTICLE
ZDB-ID	2651702-4
ISSN	2211-5463
ISSN	2211-5463
DOI	10.1002/2211-5463.13322
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Effectiveness of HEPA Filters at Removing Infectious SARS-CoV-2 from the Air.

Ueki, Hiroshi / Ujie, Michiko / Komori, Yosuke / Kato, Tatsuo / Imai, Masaki / Kawaoka, Yoshihiro

mSphere

2022 Volume 7, Issue 4, Page(s) e0008622

Abstract: Coronavirus disease 2019 (COVID-19) spreads by airborne transmission; therefore, the development and functional evaluation of air-cleaning technologies are essential for infection control. Air filtration using high-efficiency particulate air (HEPA) ... ...

Abstract	Coronavirus disease 2019 (COVID-19) spreads by airborne transmission; therefore, the development and functional evaluation of air-cleaning technologies are essential for infection control. Air filtration using high-efficiency particulate air (HEPA) filters may be effective; however, no quantitative assessment of the effectiveness of these filters in the removal of infectious severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from the air has been reported. To evaluate the removal effect of HEPA filtration on airborne SARS-CoV-2, here, we disseminated infectious SARS-CoV-2 aerosols in a test chamber in a biosafety level 3 facility and filtered the air with a HEPA-filtered air cleaner in the chamber. The air cleaner with the HEPA filter continuously removed the infectious SARS-CoV-2 from the air in a running-time-dependent manner, and the virus capture ratios were 85.38%, 96.03%, and >99.97% at 1, 2, and 7.1 ventilation volumes, respectively. The air-cleaning performance of a HEPA filter coated with an antiviral agent consisting mainly of a monovalent copper compound was also evaluated, and the capture ratio was found to be comparable to that of the conventional HEPA filter. This study provides insights into the proper use and performance of HEPA-filtered air cleaners to prevent the spread of COVID-19.
MeSH term(s)	Air Conditioning ; Antiviral Agents ; COVID-19/prevention & control ; Filtration ; Humans ; SARS-CoV-2
Chemical Substances	Antiviral Agents
Language	English
Publishing date	2022-08-10
Publishing country	United States
Document type	Journal Article
ISSN	2379-5042
ISSN (online)	2379-5042
DOI	10.1128/msphere.00086-22
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Article ; Online: Characterization of H9N2 Avian Influenza Viruses Isolated from Poultry Products in a Mouse Model.

Murakami, Jurika / Shibata, Akihiro / Neumann, Gabriele / Imai, Masaki / Watanabe, Tokiko / Kawaoka, Yoshihiro

Viruses

2022 Volume 14, Issue 4

Abstract: Low pathogenic H9N2 avian influenza viruses have spread in wild birds and poultry worldwide. Recently, the number of human cases of H9N2 virus infection has increased in China and other countries, heightening pandemic concerns. In Japan, H9N2 viruses are ...

Abstract	Low pathogenic H9N2 avian influenza viruses have spread in wild birds and poultry worldwide. Recently, the number of human cases of H9N2 virus infection has increased in China and other countries, heightening pandemic concerns. In Japan, H9N2 viruses are not yet enzootic; however, avian influenza viruses, including H5N1, H7N9, H5N6, and H9N2, have been repeatedly detected in raw poultry meat carried by international flight passengers from Asian countries to Japan. Although H9N2 virus-contaminated poultry products intercepted by the animal quarantine service at the Japan border have been characterized in chickens and ducks, the biological properties of those H9N2 viruses in mammals remain unclear. Here, we characterized the biological features of two H9N2 virus isolates [A/chicken/Japan/AQ-HE28-50/2016 (Ck/HE28-50) and A/chicken/Japan/AQ-HE28-57/2016 (Ck/HE28-57)] in a mouse model. We found that these H9N2 viruses replicate well in the respiratory tract of infected mice without adaptation, and that Ck/HE28-57 caused body weight loss in the infected mice. Our results indicate that H9N2 avian influenza viruses isolated from raw chicken meat products illegally brought to Japan can potentially infect and cause disease in mammals.
MeSH term(s)	Animals ; Chickens ; China ; Disease Models, Animal ; Influenza A Virus, H5N1 Subtype ; Influenza A Virus, H7N9 Subtype ; Influenza A Virus, H9N2 Subtype/genetics ; Influenza in Birds ; Mammals ; Mice ; Phylogeny ; Poultry ; Poultry Diseases ; Poultry Products
Language	English
Publishing date	2022-03-30
Publishing country	Switzerland
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2516098-9
ISSN	1999-4915 ; 1999-4915
ISSN (online)	1999-4915
ISSN	1999-4915
DOI	10.3390/v14040728
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