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  1. Article ; Online: Increased expression of CD38 on endothelial cells in SARS-CoV-2 infection in cynomolgus macaques.

    Nguyen, Cong Thanh / Nakayama, Misako / Ishigaki, Hirohito / Kitagawa, Yoshinori / Kakino, Akemi / Ohno, Marumi / Shingai, Masashi / Suzuki, Yasuhiko / Sawamura, Tatsuya / Kida, Hiroshi / Itoh, Yasushi

    Virology

    2024  Volume 594, Page(s) 110052

    Abstract: SARS-CoV-2 infection causes activation of endothelial cells (ECs), leading to dysmorphology and dysfunction. To study the pathogenesis of endotheliopathy, the activation of ECs in lungs of cynomolgus macaques after SARS-CoV-2 infection and changes in ... ...

    Abstract SARS-CoV-2 infection causes activation of endothelial cells (ECs), leading to dysmorphology and dysfunction. To study the pathogenesis of endotheliopathy, the activation of ECs in lungs of cynomolgus macaques after SARS-CoV-2 infection and changes in nicotinamide adenine dinucleotide (NAD) metabolism in ECs were investigated, with a focus on the CD38 molecule, which degrades NAD in inflammatory responses after SARS-CoV-2 infection. Activation of ECs was seen from day 3 after SARS-CoV-2 infection in macaques, with increases of intravascular fibrin and NAD metabolism-associated enzymes including CD38. In vitro, upregulation of CD38 mRNA in human ECs was detected after interleukin 6 (IL-6) trans-signaling induction, which was increased in the infection. In the presence of IL-6 trans-signaling stimulation, however, CD38 mRNA silencing induced significant IL-6 mRNA upregulation in ECs and promoted EC apoptosis after stimulation. These results suggest that upregulation of CD38 in patients with COVID-19 has a protective role against IL-6 trans-signaling stimulation induced by SARS-CoV-2 infection.
    MeSH term(s) Humans ; Animals ; COVID-19/metabolism ; Endothelial Cells/metabolism ; Interleukin-6/genetics ; Interleukin-6/metabolism ; NAD ; SARS-CoV-2/metabolism ; Macaca/metabolism ; RNA, Messenger/metabolism
    Chemical Substances Interleukin-6 ; NAD (0U46U6E8UK) ; RNA, Messenger
    Language English
    Publishing date 2024-03-14
    Publishing country United States
    Document type Journal Article
    ZDB-ID 200425-2
    ISSN 1096-0341 ; 0042-6822
    ISSN (online) 1096-0341
    ISSN 0042-6822
    DOI 10.1016/j.virol.2024.110052
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: GR Utilizes a Co-Chaperone Cytoplasmic CAR Retention Protein to Form an N/C Interaction.

    Ohno, Marumi / Negishi, Masahiko

    Nuclear receptor signaling

    2018  Volume 15, Page(s) 1550762918801072

    Abstract: The N-terminal domain (NTD) of nuclear receptor superfamily members has been recently reported to regulate functions of the receptor through the interaction between the NTD and the C-terminal ligand binding domain (LBD), so-called an N/C interaction. ... ...

    Abstract The N-terminal domain (NTD) of nuclear receptor superfamily members has been recently reported to regulate functions of the receptor through the interaction between the NTD and the C-terminal ligand binding domain (LBD), so-called an N/C interaction. Although this N/C interaction has been demonstrated in various nuclear receptors, eg, androgen receptor, this concept has not been observed in glucocorticoid receptor (GR). We hypothesized that GR requires its co-chaperone CCRP (cytoplasmic constitutive active/androstane receptor retention protein) to form a stable N/C interaction. This hypothesis was examined by co-immunoprecipitation assays using GR fragments overexpressing COS-1 cell lysate. Here, we demonstrated that GR undergoes the N/C interaction between the
    MeSH term(s) Amino Acid Sequence ; Animals ; COS Cells ; Chlorocebus aethiops ; Cytoplasm/metabolism ; Humans ; Protein Binding ; Protein Domains ; Protein Transport ; Receptors, Cytoplasmic and Nuclear/metabolism ; Receptors, Glucocorticoid/chemistry ; Receptors, Glucocorticoid/metabolism
    Chemical Substances Receptors, Cytoplasmic and Nuclear ; Receptors, Glucocorticoid ; constitutive androstane receptor (438XLITDI3)
    Language English
    Publishing date 2018-10-24
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Intramural
    ZDB-ID 2230618-3
    ISSN 1550-7629 ; 1550-7629
    ISSN (online) 1550-7629
    ISSN 1550-7629
    DOI 10.1177/1550762918801072
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: The elucidation of plasma lipidome profiles during severe influenza in a mouse model.

    Ohno, Marumi / Gowda, Siddabasave Gowda B / Sekiya, Toshiki / Nomura, Naoki / Shingai, Masashi / Hui, Shu-Ping / Kida, Hiroshi

    Scientific reports

    2023  Volume 13, Issue 1, Page(s) 14210

    Abstract: Although influenza virus infection has been shown to affect lipid metabolism, details remain unknown. Therefore, we elucidated the kinetic lipid profiles of mice infected with different doses of influenza virus A/Puerto Rico/8/34 (H1N1) (PR8) by ... ...

    Abstract Although influenza virus infection has been shown to affect lipid metabolism, details remain unknown. Therefore, we elucidated the kinetic lipid profiles of mice infected with different doses of influenza virus A/Puerto Rico/8/34 (H1N1) (PR8) by measuring multiple lipid molecular species using untargeted lipidomic analysis. C57BL/6 male mice were intranasally infected with PR8 virus at 50 or 500 plaque-forming units to cause sublethal or lethal influenza, respectively. Plasma and tissue samples were collected at 1, 3, and 6 days post-infection (dpi), and comprehensive lipidomic analysis was performed using high-performance liquid chromatography-linear trap quadrupole-Orbitrap mass spectrometry, as well as gene expression analyses. The most prominent feature of the lipid profile in lethally infected mice was the elevated plasma concentrations of phosphatidylethanolamines (PEs) containing polyunsaturated fatty acid (PUFA) at 3 dpi. Furthermore, the facilitation of PUFA-containing phospholipid production in the lungs, but not in the liver, was suggested by gene expression and lipidomic analysis of tissue samples. Given the increased plasma or serum levels of PUFA-containing PEs in patients with other viral infections, especially in severe cases, the elevation of these phospholipids in circulation could be a biomarker of infection and the severity of infectious diseases.
    MeSH term(s) Male ; Animals ; Mice ; Humans ; Mice, Inbred C57BL ; Influenza, Human ; Lipidomics ; Influenza A Virus, H1N1 Subtype ; Disease Models, Animal ; Lipids
    Chemical Substances Lipids
    Language English
    Publishing date 2023-08-30
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2615211-3
    ISSN 2045-2322 ; 2045-2322
    ISSN (online) 2045-2322
    ISSN 2045-2322
    DOI 10.1038/s41598-023-41055-y
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Inactivated Whole Virus Particle Influenza Vaccine Induces Anti-Neuraminidase Antibodies That May Contribute to Cross-Protection against Heterologous Virus Infection

    Chimuka Handabile / Toshiki Sekiya / Naoki Nomura / Marumi Ohno / Tomomi Kawakita / Masashi Shingai / Hiroshi Kida

    Vaccines, Vol 10, Iss 804, p

    2022  Volume 804

    Abstract: Despite the use of vaccines, seasonal influenza remains a risk to public health. We previously proposed the inactivated whole virus particle vaccine (WPV) as an alternative to the widely used split vaccine (SV) for the control of seasonal and pandemic ... ...

    Abstract Despite the use of vaccines, seasonal influenza remains a risk to public health. We previously proposed the inactivated whole virus particle vaccine (WPV) as an alternative to the widely used split vaccine (SV) for the control of seasonal and pandemic influenza based on the superior priming potency of WPV to that of SV. In this study, we further examined and compared the immunological potency of monovalent WPV and SV of A/California/7/2009 (X-179A) (H1N1) pdm09 (CA/09) to generate immune responses against heterologous viruses, A/Singapore/GP1908/2015 (IVR-180) (H1N1) pdm09 (SG/15), and A/duck/Hokkaido/Vac-3/2007 (H5N1) (DH/07) in mice. Following challenge with a lethal dose of heterologous SG/15, lower virus titer in the lungs and milder weight loss were observed in WPV-vaccinated mice than in SV-vaccinated ones. To investigate the factors responsible for the differences in the protective effect against SG/15, the sera of vaccinated mice were analyzed by hemagglutination-inhibition (HI) and neuraminidase-inhibition (NI) assays to evaluate the antibodies induced against viral hemagglutinin (HA) and neuraminidase (NA), respectively. While the two vaccines induced similar levels of HI antibodies against SG/15 after the second vaccination, only WPV-vaccinated mice induced significantly higher titers of NI antibodies against the strain. Furthermore, given the significant elevation of NI antibody titers against DH/07, an H5N1 avian influenza virus, WPV was also demonstrated to induce NA-inhibiting antibodies that recognize NA of divergent strains. This could be explained by the higher conservation of epitopes of NA among strains than for HA. Taking these findings together, NA-specific antibodies induced by WPV may have contributed to better protection from infection with heterologous influenza virus SG/15, compared with SV. The present results indicate that WPV is an effective vaccine for inducing antibodies against both HA and NA of heterologous viruses and may be a useful vaccine to conquer vaccine strain mismatch.
    Keywords inactivated whole virus particle influenza vaccine ; anti-neuraminidase antibodies ; cross-protection ; Medicine ; R
    Subject code 616 ; 570
    Language English
    Publishing date 2022-05-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  5. Article ; Online: Determination of short-chain fatty acids by N,N-dimethylethylenediamine derivatization combined with liquid chromatography/mass spectrometry and their implication in influenza virus infection.

    Gowda, Divyavani / Li, Yonghan / B Gowda, Siddabasave Gowda / Ohno, Marumi / Chiba, Hitoshi / Hui, Shu-Ping

    Analytical and bioanalytical chemistry

    2022  Volume 414, Issue 22, Page(s) 6419–6430

    Abstract: Short-chain fatty acids (SCFAs) are the end products of the fermentation of complex carbohydrates by the gut microbiota. Although SCFAs are recognized as important markers to elucidate the link between gut health and disease, it has been difficult to ... ...

    Abstract Short-chain fatty acids (SCFAs) are the end products of the fermentation of complex carbohydrates by the gut microbiota. Although SCFAs are recognized as important markers to elucidate the link between gut health and disease, it has been difficult to analyze SCFAs with mass spectrometry technologies due to their poor ionization efficiency and high volatility. Here, we present a novel and sensitive method for the quantification of SCFAs, including C2-C6 SCFAs and their hydroxy derivatives, by liquid chromatography/tandem mass spectrometry (LC-MS/MS) upon N,N-dimethylethylenediamine (DMED) derivatization with a run time of 10 min. Moreover, the quantification method of DMED-derivatized SCFAs in intestinal contents using isotope-labeled internal standards was also established. The method validation was performed by analyzing spiked intestinal samples; the limits of detection and quantification of SCFAs with this method were found to be 0.5 and 5 fmol, respectively; the recovery was greater than 80% and good linearity (0.9932 to 0.9979) of calibration curves was obtained over the range from 0.005 to 5000 pmol/μL; the intraday and interday precisions were achieved in the range of 1-5%. Furthermore, the validated method was applied to analyze SCFAs in the cecum and colon contents of mice infected with the influenza virus. The results showed that the concentration of most of the SCFAs tested here decreased significantly in a time-dependent manner after the infection, suggesting a possibility that SCFAs in intestinal samples could be used as severe disease markers. Overall, we here successfully developed a simple, fast, and sensitive method for SCFA analysis by LC-MS/MS combined with DMED derivatization. The method for the quantification of SCFAs will be a useful tool for both basic research and clinical studies.
    MeSH term(s) Animals ; Chromatography, High Pressure Liquid ; Chromatography, Liquid/methods ; Ethylenediamines ; Fatty Acids, Volatile/analysis ; Humans ; Influenza, Human ; Mice ; Orthomyxoviridae ; Tandem Mass Spectrometry/methods
    Chemical Substances Ethylenediamines ; Fatty Acids, Volatile ; dimethylethylenediamine (110-70-3)
    Language English
    Publishing date 2022-07-16
    Publishing country Germany
    Document type Journal Article
    ZDB-ID 201093-8
    ISSN 1618-2650 ; 0016-1152 ; 0372-7920
    ISSN (online) 1618-2650
    ISSN 0016-1152 ; 0372-7920
    DOI 10.1007/s00216-022-04217-x
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article: Inactivated Whole Virus Particle Influenza Vaccine Induces Anti-Neuraminidase Antibodies That May Contribute to Cross-Protection against Heterologous Virus Infection.

    Handabile, Chimuka / Sekiya, Toshiki / Nomura, Naoki / Ohno, Marumi / Kawakita, Tomomi / Shingai, Masashi / Kida, Hiroshi

    Vaccines

    2022  Volume 10, Issue 5

    Abstract: Despite the use of vaccines, seasonal influenza remains a risk to public health. We previously proposed the inactivated whole virus particle vaccine (WPV) as an alternative to the widely used split vaccine (SV) for the control of seasonal and pandemic ... ...

    Abstract Despite the use of vaccines, seasonal influenza remains a risk to public health. We previously proposed the inactivated whole virus particle vaccine (WPV) as an alternative to the widely used split vaccine (SV) for the control of seasonal and pandemic influenza based on the superior priming potency of WPV to that of SV. In this study, we further examined and compared the immunological potency of monovalent WPV and SV of A/California/7/2009 (X-179A) (H1N1) pdm09 (CA/09) to generate immune responses against heterologous viruses, A/Singapore/GP1908/2015 (IVR-180) (H1N1) pdm09 (SG/15), and A/duck/Hokkaido/Vac-3/2007 (H5N1) (DH/07) in mice. Following challenge with a lethal dose of heterologous SG/15, lower virus titer in the lungs and milder weight loss were observed in WPV-vaccinated mice than in SV-vaccinated ones. To investigate the factors responsible for the differences in the protective effect against SG/15, the sera of vaccinated mice were analyzed by hemagglutination-inhibition (HI) and neuraminidase-inhibition (NI) assays to evaluate the antibodies induced against viral hemagglutinin (HA) and neuraminidase (NA), respectively. While the two vaccines induced similar levels of HI antibodies against SG/15 after the second vaccination, only WPV-vaccinated mice induced significantly higher titers of NI antibodies against the strain. Furthermore, given the significant elevation of NI antibody titers against DH/07, an H5N1 avian influenza virus, WPV was also demonstrated to induce NA-inhibiting antibodies that recognize NA of divergent strains. This could be explained by the higher conservation of epitopes of NA among strains than for HA. Taking these findings together, NA-specific antibodies induced by WPV may have contributed to better protection from infection with heterologous influenza virus SG/15, compared with SV. The present results indicate that WPV is an effective vaccine for inducing antibodies against both HA and NA of heterologous viruses and may be a useful vaccine to conquer vaccine strain mismatch.
    Language English
    Publishing date 2022-05-19
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2703319-3
    ISSN 2076-393X
    ISSN 2076-393X
    DOI 10.3390/vaccines10050804
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  7. Article ; Online: Critical role of oxidized LDL receptor-1 in intravascular thrombosis in a severe influenza mouse model.

    Ohno, Marumi / Kakino, Akemi / Sekiya, Toshiki / Nomura, Naoki / Shingai, Masashi / Sawamura, Tatsuya / Kida, Hiroshi

    Scientific reports

    2021  Volume 11, Issue 1, Page(s) 15675

    Abstract: Although coagulation abnormalities, including microvascular thrombosis, are thought to contribute to tissue injury and single- or multiple-organ dysfunction in severe influenza, the detailed mechanisms have yet been clarified. This study evaluated ... ...

    Abstract Although coagulation abnormalities, including microvascular thrombosis, are thought to contribute to tissue injury and single- or multiple-organ dysfunction in severe influenza, the detailed mechanisms have yet been clarified. This study evaluated influenza-associated abnormal blood coagulation utilizing a severe influenza mouse model. After infecting C57BL/6 male mice with intranasal applications of 500 plaque-forming units of influenza virus A/Puerto Rico/8/34 (H1N1; PR8), an elevated serum level of prothrombin fragment 1 + 2, an indicator for activated thrombin generation, was observed. Also, an increased gene expression of oxidized low-density lipoprotein (LDL) receptor-1 (Olr1), a key molecule in endothelial dysfunction in the progression of atherosclerosis, was detected in the aorta of infected mice. Body weight decrease, serum levels of cytokines and chemokines, viral load, and inflammation in the lungs of infected animals were similar between wild-type and Olr1 knockout (KO) mice. In contrast, the elevation of prothrombin fragment 1 + 2 levels in the sera and intravascular thrombosis in the lungs by PR8 virus infection were not induced in KO mice. Collectively, the results indicated that OLR1 is a critical host factor in intravascular thrombosis as a pathogeny of severe influenza. Thus, OLR1 is a promising novel therapeutic target for thrombosis during severe influenza.
    MeSH term(s) Animals ; Biomarkers ; Blood Coagulation ; Cytokines/blood ; Disease Models, Animal ; Disease Susceptibility ; Mice ; Mice, Knockout ; Orthomyxoviridae Infections/complications ; Orthomyxoviridae Infections/diagnosis ; Orthomyxoviridae Infections/virology ; Partial Thromboplastin Time ; Scavenger Receptors, Class E/genetics ; Scavenger Receptors, Class E/metabolism ; Severity of Illness Index ; Thrombin/biosynthesis ; Thrombosis/diagnosis ; Thrombosis/etiology ; Thrombosis/metabolism ; Viral Load
    Chemical Substances Biomarkers ; Cytokines ; Olr1 protein, mouse ; Scavenger Receptors, Class E ; Thrombin (EC 3.4.21.5)
    Language English
    Publishing date 2021-08-03
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2615211-3
    ISSN 2045-2322 ; 2045-2322
    ISSN (online) 2045-2322
    ISSN 2045-2322
    DOI 10.1038/s41598-021-95046-y
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: Detection and Structural Characterization of SFAHFA Homologous Series in Mouse Colon Contents by LTQ-Orbitrap-MS and Their Implication in Influenza Virus Infection.

    B Gowda, Siddabasave Gowda / Gowda, Divyavani / Ohno, Marumi / Liang, Chongsheng / Chiba, Hitoshi / Hui, Shu-Ping

    Journal of the American Society for Mass Spectrometry

    2021  Volume 32, Issue 8, Page(s) 2196–2205

    Abstract: Fatty acid esters of hydroxy fatty acids (FAHFAs) are a new class of endogenous lipids with promising physiological functions in mammals. We previously introduced a new type of lipids to this family called short-chain fatty acid esters of hydroxy fatty ... ...

    Abstract Fatty acid esters of hydroxy fatty acids (FAHFAs) are a new class of endogenous lipids with promising physiological functions in mammals. We previously introduced a new type of lipids to this family called short-chain fatty acid esters of hydroxy fatty acids (SFAHFAs), branching specific to the C2 carbon of a long-chain fatty acid (≥C20). In this study, we discovered a homologous series of SFAHFAs comprising C16-C26 hydroxy fatty acids esterified with short-chain fatty acids (C2-C5) in mouse colon contents. The detected SFAHFAs were characterized by high-resolution mass spectrometry with MS
    MeSH term(s) Animals ; Chlorobenzoates/chemistry ; Colon/chemistry ; Colon/metabolism ; Colon/virology ; Epoxy Compounds/chemistry ; Esters/analysis ; Esters/chemistry ; Fatty Acids, Volatile/analysis ; Fatty Acids, Volatile/chemistry ; Fatty Acids, Volatile/metabolism ; Influenza A Virus, H1N1 Subtype/pathogenicity ; Male ; Mass Spectrometry/methods ; Mice, Inbred C57BL ; Multivariate Analysis ; Orthomyxoviridae Infections/metabolism ; Mice
    Chemical Substances Chlorobenzoates ; Epoxy Compounds ; Esters ; Fatty Acids, Volatile ; 3-chloroperbenzoic acid (G203D4H1RB)
    Language English
    Publishing date 2021-06-25
    Publishing country United States
    Document type Journal Article
    ZDB-ID 1073671-2
    ISSN 1879-1123 ; 1044-0305
    ISSN (online) 1879-1123
    ISSN 1044-0305
    DOI 10.1021/jasms.1c00138
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  9. Article ; Online: Critical role of oxidized LDL receptor-1 in intravascular thrombosis in a severe influenza mouse model

    Marumi Ohno / Akemi Kakino / Toshiki Sekiya / Naoki Nomura / Masashi Shingai / Tatsuya Sawamura / Hiroshi Kida

    Scientific Reports, Vol 11, Iss 1, Pp 1-

    2021  Volume 10

    Abstract: Abstract Although coagulation abnormalities, including microvascular thrombosis, are thought to contribute to tissue injury and single- or multiple-organ dysfunction in severe influenza, the detailed mechanisms have yet been clarified. This study ... ...

    Abstract Abstract Although coagulation abnormalities, including microvascular thrombosis, are thought to contribute to tissue injury and single- or multiple-organ dysfunction in severe influenza, the detailed mechanisms have yet been clarified. This study evaluated influenza-associated abnormal blood coagulation utilizing a severe influenza mouse model. After infecting C57BL/6 male mice with intranasal applications of 500 plaque-forming units of influenza virus A/Puerto Rico/8/34 (H1N1; PR8), an elevated serum level of prothrombin fragment 1 + 2, an indicator for activated thrombin generation, was observed. Also, an increased gene expression of oxidized low-density lipoprotein (LDL) receptor-1 (Olr1), a key molecule in endothelial dysfunction in the progression of atherosclerosis, was detected in the aorta of infected mice. Body weight decrease, serum levels of cytokines and chemokines, viral load, and inflammation in the lungs of infected animals were similar between wild-type and Olr1 knockout (KO) mice. In contrast, the elevation of prothrombin fragment 1 + 2 levels in the sera and intravascular thrombosis in the lungs by PR8 virus infection were not induced in KO mice. Collectively, the results indicated that OLR1 is a critical host factor in intravascular thrombosis as a pathogeny of severe influenza. Thus, OLR1 is a promising novel therapeutic target for thrombosis during severe influenza.
    Keywords Medicine ; R ; Science ; Q
    Subject code 616
    Language English
    Publishing date 2021-08-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  10. Article ; Online: Extraction of the CDRH3 sequence of the mouse antibody repertoire selected upon influenza virus infection by subtraction of the background antibody repertoire.

    Shingai, Masashi / Iida, Sayaka / Kawai, Naoko / Kawahara, Mamiko / Sekiya, Toshiki / Ohno, Marumi / Nomura, Naoki / Handabile, Chimuka / Kawakita, Tomomi / Omori, Ryosuke / Yamagishi, Junya / Sano, Kaori / Ainai, Akira / Suzuki, Tadaki / Ohnishi, Kazuo / Ito, Kimihito / Kida, Hiroshi

    Journal of virology

    2024  Volume 98, Issue 3, Page(s) e0199523

    Abstract: Historically, antibody reactivity to pathogens and vaccine antigens has been evaluated using serological measurements of antigen-specific antibodies. However, it is difficult to evaluate all antibodies that contribute to various functions in a single ... ...

    Abstract Historically, antibody reactivity to pathogens and vaccine antigens has been evaluated using serological measurements of antigen-specific antibodies. However, it is difficult to evaluate all antibodies that contribute to various functions in a single assay, such as the measurement of the neutralizing antibody titer. Bulk antibody repertoire analysis using next-generation sequencing is a comprehensive method for analyzing the overall antibody response; however, it is unreliable for estimating antigen-specific antibodies due to individual variation. To address this issue, we propose a method to subtract the background signal from the repertoire of data of interest. In this study, we analyzed changes in antibody diversity and inferred the heavy-chain complementarity-determining region 3 (CDRH3) sequences of antibody clones that were selected upon influenza virus infection in a mouse model using bulk repertoire analysis. A decrease in the diversity of the antibody repertoire was observed upon viral infection, along with an increase in neutralizing antibody titers. Using kernel density estimation of sequences in a high-dimensional sequence space with background signal subtraction, we identified several clusters of CDRH3 sequences induced upon influenza virus infection. Most of these repertoires were detected more frequently in infected mice than in uninfected control mice, suggesting that infection-specific antibody sequences can be extracted using this method. Such an accurate extraction of antigen- or infection-specific repertoire information will be a useful tool for vaccine evaluation in the future.
    Importance: As specific interactions between antigens and cell-surface antibodies trigger the proliferation of B-cell clones, the frequency of each antibody sequence in the samples reflects the size of each clonal population. Nevertheless, it is extremely difficult to extract antigen-specific antibody sequences from the comprehensive bulk antibody sequences obtained from blood samples due to repertoire bias influenced by exposure to dietary antigens and other infectious agents. This issue can be addressed by subtracting the background noise from the post-immunization or post-infection repertoire data. In the present study, we propose a method to quantify repertoire data from comprehensive repertoire data. This method allowed subtraction of the background repertoire, resulting in more accurate extraction of expanded antibody repertoires upon influenza virus infection. This accurate extraction of antigen- or infection-specific repertoire information is a useful tool for vaccine evaluation.
    MeSH term(s) Animals ; Mice ; Antibodies, Neutralizing/blood ; Antibodies, Neutralizing/chemistry ; Antibodies, Neutralizing/immunology ; Antibodies, Viral/blood ; Antibodies, Viral/chemistry ; Antibodies, Viral/immunology ; B-Lymphocytes/cytology ; B-Lymphocytes/immunology ; Clone Cells/cytology ; Clone Cells/immunology ; Complementarity Determining Regions/immunology ; Influenza Vaccines/immunology ; Orthomyxoviridae/immunology ; Orthomyxoviridae Infections/blood ; Orthomyxoviridae Infections/immunology ; Orthomyxoviridae Infections/virology
    Chemical Substances Antibodies, Neutralizing ; Antibodies, Viral ; Complementarity Determining Regions ; Influenza Vaccines
    Language English
    Publishing date 2024-02-07
    Publishing country United States
    Document type Journal Article
    ZDB-ID 80174-4
    ISSN 1098-5514 ; 0022-538X
    ISSN (online) 1098-5514
    ISSN 0022-538X
    DOI 10.1128/jvi.01995-23
    Database MEDical Literature Analysis and Retrieval System OnLINE

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