Faculty Profiles - Kyoko (Tsukiyama-)Kohara

Papers - Kyoko (Tsukiyama-)Kohara

Division display 61 - 80 of about 149 ／ All the affair displays >>

Mohammad Enamul Hoque Kayesh, Michinori Kohara, Kyoko Tsukiyama-Kohara . Toll-Like Receptor Response to Hepatitis B Virus Infection and Potential of TLR Agonists as Immunomodulators for Treating Chronic Hepatitis B: An Overview. . International journal of molecular sciences22 ( 19 ) 2021.9Reviewed International journal

Language：English Publishing type：Research paper (scientific journal)

Chronic hepatitis B virus (HBV) infection remains a major global health problem. The immunopathology of the disease, especially the interplay between HBV and host innate immunity, is poorly understood. Moreover, inconsistent literature on HBV and host innate immunity has led to controversies. However, recently, there has been an increase in the number of studies that have highlighted the link between innate immune responses, including Toll-like receptors (TLRs), and chronic HBV infection. TLRs are the key sensing molecules that detect pathogen-associated molecular patterns and regulate the induction of pro- and anti-inflammatory cytokines, thereby shaping the adaptive immunity. The suppression of TLR response has been reported in patients with chronic hepatitis B (CHB), as well as in other models, including tree shrews, suggesting an association of TLR response in HBV chronicity. Additionally, TLR agonists have been reported to improve the host innate immune response against HBV infection, highlighting the potential of these agonists as immunomodulators for enhancing CHB treatment. In this study, we discuss the current understanding of host innate immune responses during HBV infection, particularly focusing on the TLR response and TLR agonists as immunomodulators.

DOI： 10.3390/ijms221910462

Scopus

PubMed

Islam Abbadi, Mustapha Lkhider, Bouchra Kitab, Khalid Jabboua, Imane Zaidane, Asmaa Haddaji, Sabrine Nacer, Aya Matsuu, Pascal Pineau, Kyoko Tsukiyama-Kohara, Soumaya Benjelloun, Sayeh Ezzikouri . Non-primate hepacivirus transmission and prevalence: Novel findings of virus circulation in horses and dogs in Morocco. . Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases93 104975 - 104975 2021.9Reviewed International journal

Language：English Publishing type：Research paper (scientific journal)

Non-primate hepacivirus (NPHV) is a homolog of hepatitis C virus and has been isolated from dogs and horses. Data on NPHV prevalence and distribution are not complete, and there is a particular lack of reports from the African continent. The present study represents the first investigation of NPHV prevalence in horses and dogs in North Africa. Blood was collected from 172 horses and 36 dogs at different locations in Morocco, and screened for NPHV RNA using nested PCR targeting 5'UTR and NS3 regions and analyzed for anti-NPHV NS3 antibody using a Gaussia luciferase immunoprecipitation system-to determine seroprevalence. Eight sequences of the NS3 region isolated from positive serum samples were targeted for phylogenetic analysis. Horses and dogs showed respective NPHV RNA positivity rates of 10.5% and 5.5%, and seroprevalences of 65.7% and 8.33%. Juvenile horses appeared more susceptible to infection, with a 23.5% NHPV RNA positivity rate. Seropositivity was more extensive in mares than stallions (77.14% vs. 46.27%, p < 0.0001). Phylogenetically, that NPHV NS3 genes isolated from horses and dog are clustered together. The NPHV strains we detected showed no correlation with geographic location within Morocco. In conclusion, Moroccan horses showed much evidence of previous and/or current NPHV infection, with young age and female sex as noted potential risk factors. Interestingly, NPHV is circulating in dogs as well as horses, suggesting that it has crossed species barriers and that horses and dogs are potential vectors by which an ancestor to hepatitis C virus was transmitted into human populations.

DOI： 10.1016/j.meegid.2021.104975

Scopus

PubMed

ケアシュ・モハメド, 尼子豊, ハシェム・モハメド, 山本直樹, 杉山真也, 溝上雅史, 小原道法, 小原恭子 . B型肝炎ウイルスcccDNAを標的としたCRISPR/Cas9システムの生体内送達法の開発 . 日本癌学会総会記事80回 [J3 - 5] 2021.9Reviewed International journal

Honda T, Gomi S, Yamane D, Yasui F, Yamamoto T, Munakata T, Itoh Y, Ogasawara K, Sanada T, Yamaji K, Yasutomi Y, Tsukiyama-Kohara K, Kohara M. . Development and Characterization of a Highly Sensitive NanoLuciferase-Based Immunoprecipitation System for the Detection of Anti-Influenza Virus HA . mSphere6 ( 3 ) e1342-20 2021.5Reviewed

Tomoko Honda, Sumiko Gomi, Daisuke Yamane, Fumihiko Yasui, Takuya Yamamoto, Tsubasa Munakata, Yasushi Itoh, Kazumasa Ogasawara, Takahiro Sanada, Kenzaburo Yamaji, Yasuhiro Yasutomi, Kyoko Tsukiyama-Kohara, Michinori Kohara . Development and Characterization of a Highly Sensitive NanoLuciferase-Based Immunoprecipitation System for the Detection of Anti-Influenza Virus HA Antibodies. . mSphere6 ( 3 ) 1 - 14 2021.5Reviewed International journal

Language：English Publishing type：Research paper (scientific journal)

Antibody detection is crucial for monitoring host immune responses to specific pathogen antigens (Ags) and evaluating vaccine efficacies. The luciferase immunoprecipitation system (LIPS) was developed for sensitive detection of Ag-specific antibodies in sera from various species. In this study, we describe NanoLIPS, an improved LIPS assay based on NanoLuciferase (NLuc), and employ the assay for monitoring antibody responses following influenza virus infection or vaccination. We generated recombinant influenza virus hemagglutinin (HA) proteins tagged with N-terminal (N-NLuc-HA) or C-terminal (C-NLuc-HA) NLuc reporters. NLuc-HA yielded an at least 20-fold higher signal-to-noise ratio than did a LIPS assay employing a recombinant HA-Gaussia princeps luciferase (GLuc) fusion protein. NanoLIPS-based detection of anti-HA antibodies yielded highly reproducible results with a broad dynamic range. The levels of antibodies against C-NLuc-HA generated by mice vaccinated with recombinant vaccinia virus DIs strain expressing an influenza virus HA protein (rDIs-HA) was significantly correlated with the protective effect elicited by the rDIs-HA vaccine. C-NLuc-HA underwent glycosylation with native conformations and assembly to form a trimeric structure and was detected by monoclonal antibodies that detect conformational epitopes present on the globular head or stalk domain of HA. Therefore, NanoLIPS is applicable for evaluating vaccine efficacy. We also showed that C-NLuc-HA is applicable for detection of HA-specific antibodies in sera from various experimental species, including mouse, cynomolgus macaque, and tree shrew. Thus, NanoLIPS-based detection of HA offers a simple and high-sensitivity method that detects native conformational epitopes and can be used in various experimental animal models.IMPORTANCE Influenza virus HA-specific antibodies can be detected via the hemagglutination inhibition (HI) assay, the neutralization (NT) assay, and the enzyme-linked immunosorbent assay (ELISA). However, these assays have some drawbacks, including narrow dynamic range and the requirement for large amounts of sera. As an alternative to an ELISA-based method, luciferase immunoprecipitation system (LIPS) was developed. We focused on NanoLuciferase (NLuc), which has a small size, higher intensity, and longer stability. In this study, we developed a technically feasible and highly sensitive method for detecting influenza virus-specific antibodies using a NLuc-tagged recombinant HA protein produced in mammalian cells. HA with a C-terminal NLuc extension (C-NLuc-HA) was glycosylated and formed trimeric complexes when expressed in mammalian cells. Furthermore, C-NLuc-HA was recognized not only by monoclonal antibodies that bind to the globular head domain but also by those that bind to the stalk domain. We also demonstrated that the data obtained by this assay correlate with the protection of an experimental vaccine in animal models.

DOI： 10.1128/mSphere.01342-20

Scopus

PubMed

Makoto Saito, Yasushi Itoh, Fumihiko Yasui, Tsubasa Munakata, Daisuke Yamane, Makoto Ozawa, Risa Ito, Takayuki Katoh, Hirohito Ishigaki, Misako Nakayama, Shintaro Shichinohe, Kenzaburo Yamaji, Naoki Yamamoto, Ai Ikejiri, Tomoko Honda, Takahiro Sanada, Yoshihiro Sakoda, Hiroshi Kida, Thi Quynh Mai Le, Yoshihiro Kawaoka, Kazumasa Ogasawara, Kyoko Tsukiyama-Kohara, Hiroaki Suga, Michinori Kohara . Macrocyclic peptides exhibit antiviral effects against influenza virus HA and prevent pneumonia in animal models. . Nature communications12 ( 1 ) 2654 - 2654 2021.5Reviewed International journal

Language：English Publishing type：Research paper (scientific journal)

Most anti-influenza drugs currently used, such as oseltamivir and zanamivir, inhibit the enzymatic activity of neuraminidase. However, neuraminidase inhibitor-resistant viruses have already been identified from various influenza virus isolates. Here, we report the development of a class of macrocyclic peptides that bind the influenza viral envelope protein hemagglutinin, named iHA. Of 28 iHAs examined, iHA-24 and iHA-100 have inhibitory effects on the in vitro replication of a wide range of Group 1 influenza viruses. In particular, iHA-100 bifunctionally inhibits hemagglutinin-mediated adsorption and membrane fusion through binding to the stalk domain of hemagglutinin. Moreover, iHA-100 shows powerful efficacy in inhibiting the growth of highly pathogenic influenza viruses and preventing severe pneumonia at later stages of infection in mouse and non-human primate cynomolgus macaque models. This study shows the potential for developing cyclic peptides that can be produced more efficiently than antibodies and have multiple functions as next-generation, mid-sized biomolecules.

DOI： 10.1038/s41467-021-22964-w

Scopus

PubMed

Toll-Like Receptor and Cytokine Responses to Infection with Endogenous and Exogenous Koala Retrovirus, and Vaccination as a Control Strategy . Curr Issues Mol Biol. 43 ( 1 ) 52 - 64 2021.4Reviewed International coauthorship

Md Abul Hashem1, 2, 3, Mohammad Enamul Hoque Kayesh1, 2, 4, Fumie Maetani5, Taiki Eiei5, Kyoya Mochizuki5, Shinsaku Ochiai5, Ayaka Ito5, Nanao Ito5, Hiroko Sakurai5, Takayuki Asai5 and Kyoko Tsukiyama-Kohara . Koala retrovirus (KoRV) subtypes and their impact on captive koala (Phascolarctos cinereus) health . Archives of Virologyaccepted 2021.4Reviewed

Mohammad Enamul Hoque Kayesh 1,2 , Md Abul Hashem 1,3,4 and Kyoko Tsukiyama-Kohara . Toll-Like Receptor Expression Profiles in Koala (Phascolarctos cinereus) Peripheral Blood Mononuclear Cells Infected with Multiple KoRV Subtypes . 11 983 2021.4Reviewed

Mohammad Enamul Hoque Kayesh, Md Abul Hashem, Kyoko Tsukiyama-Kohara . Toll-Like Receptor Expression Profiles in Koala (Phascolarctos cinereus) Peripheral Blood Mononuclear Cells Infected with Multiple KoRV Subtypes. . Animals : an open access journal from MDPI11 ( 4 ) 2021.4Reviewed International journal

Language：English Publishing type：Research paper (scientific journal)

Toll-like receptors (TLRs), evolutionarily conserved pattern recognition receptors, play an important role in innate immunity by recognizing microbial pathogen-associated molecular patterns. Koala retrovirus (KoRV), a major koala pathogen, exists in both endogenous (KoRV-A) and exogenous forms (KoRV-B to J). However, the expression profile of TLRs in koalas infected with KoRV-A and other subtypes is yet to characterize. Here, we investigated TLR expression profiles in koalas with a range of subtype infection profiles (KoRV-A only vs. KoRV-A with KoRV-B and/or -C). To this end, we cloned partial sequences for TLRs (TLR2-10 and TLR13), developed real-time PCR assays, and determined TLRs mRNA expression patterns in koala PBMCs and/or tissues. All the reported TLRs for koala were expressed in PBMCs, and variations in TLR expression were observed in koalas infected with exogenous subtypes (KoRV-B and KoRV-C) compared to the endogenous subtype (KoRV-A) only, which indicates the implications of TLRs in KoRV infection. TLRs were also found to be differentially expressed in koala tissues. This is the first report of TLR expression profiles in koala, which provides insights into koala's immune response to KoRV infection that could be utilized for the future exploitation of TLR modulators in the maintenance of koala health.

DOI： 10.3390/ani11040983

Scopus

PubMed

Nagai M, Okabayashi T, Akagami M, Matsuu A, Fujimoto Y, Hashem MA, Mekata H, Nakao R, Matsuno K, Katayama Y, Oba M, Omatsu T, Asai T, Nakagawa K, Ito H, Madarame H, Kawai K, Ito T, Nonaka N, Tsukiyama-Kohara K, Inoshima Y, Mizutani T, Misawa N. . Metagenomic identification, sequencing, and genome analysis of porcine hepe-astroviruses (bastroviruses) in porcine feces in Japan . Infect Genet Evol.88 104664 2021.3Reviewed

Makoto Nagai, Tamaki Okabayashi, Masataka Akagami, Aya Matsuu, Yoshikazu Fujimoto, Md Abul Hashem, Hirohisa Mekata, Ryo Nakao, Keita Matsuno, Yukie Katayama, Mami Oba, Tsutomu Omatsu, Tetsuo Asai, Keisuke Nakagawa, Hiroshi Ito, Hiroo Madarame, Kazuhiro Kawai, Toshihiro Ito, Nariaki Nonaka, Kyoko Tsukiyama-Kohara, Yasuo Inoshima, Tetsuya Mizutani, Naoaki Misawa . Metagenomic identification, sequencing, and genome analysis of porcine hepe-astroviruses (bastroviruses) in porcine feces in Japan. . Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases88 104664 - 104664 2021.3Reviewed International journal

Language：English Publishing type：Research paper (scientific journal)

Recently, hepe-astrovirus-like RNA viruses named bastroviruses (BastVs), have been found in human, pig, bat, and rat fecal samples. In this study, we determined nearly complete genome sequences of four BastVs in the feces of healthy pigs. Genetic characterization revealed that these porcine BastVs (PBastVs) and BastVs from other animals including humans, had the same genome organization, that is, they contained three predicted conserved domains of viral methyltransferase, RNA helicase, and RdRp in the nonstructural ORF1 and the astrovirus capsid domain in the structural ORF2. Phylogenetic analyses using RNA-dependent RNA polymerase and the capsid region revealed that PBastVs branched with bat and rat BastVs; however, the groups formed by each host were distantly related to human BastVs. Pairwise amino acid sequence comparison demonstrated that PBastVs shared 95.2-98.6% and 76.1-95.5% sequence identity among each other in the ORF1 and ORF2 regions, respectively; the sequence identities between PBastVs and BastVs from other animals were 21.4-42.5% and 9.1-20.6% in the ORF1 and ORF2 regions, respectively. This suggested that BastVs were derived from a common ancestor but evolved independently in each host population during a prolonged period. Putative recombination events were identified in the PBastV genome, suggesting that PBastVs gain sequence diversity and flexibility through recombination events. In an analysis of previously obtained metagenomic data, PBastV sequence reads were detected in 7.3% (23/315) of fecal samples from pigs indicating that PBastVs are distributed among pig populations in Japan.

DOI： 10.1016/j.meegid.2020.104664

Scopus

PubMed

Suzuki Y, Onuma H, Sato R, Sato Y, Hashiba A, Maeki M, Tokeshi M, Kayesh MEH, Kohara M, Tsukiyama-Kohara K, Harashima H. . Lipid nanoparticles loaded with ribonucleoprotein-oligonucleotide complexes synthesized using a microfluidic device exhibit robust genome editing and hepatitis B virus inhibition. . 330 67 - 71 2021.2Reviewed

Yuichi Suzuki, Haruno Onuma, Risa Sato, Yusuke Sato, Akari Hashiba, Masatoshi Maeki, Manabu Tokeshi, Mohammad Enamul Hoque Kayesh, Michinori Kohara, Kyoko Tsukiyama-Kohara, Hideyoshi Harashima . Lipid nanoparticles loaded with ribonucleoprotein-oligonucleotide complexes synthesized using a microfluidic device exhibit robust genome editing and hepatitis B virus inhibition. . Journal of controlled release : official journal of the Controlled Release Society330 61 - 71 2021.2Reviewed International journal

Language：English Publishing type：Research paper (scientific journal)

The clustered regularly interspaced short palindromic repeats (CRISPR)-associated (Cas) system has considerable therapeutic potential for use in treating a wide range of intractable genetic and infectious diseases including hepatitis B virus (HBV) infections. While non-viral delivery technologies for the CRISPR/Cas system are expected to have clinical applications, difficulties associated with the clinically relevant synthesis of formulations and the poor efficiency of delivery severely hinder therapeutic genome editing. We report herein on the production of a lipid nanoparticle (LNP)-based CRISPR/Cas ribonucleoprotein (RNP) delivery nanoplatform synthesized using a clinically relevant mixer-equipped microfluidic device. DNA cleavage activity and the aggregation of Cas enzymes was completely avoided under the optimized synthetic conditions. The optimized formulation, which was identified through 2 steps of design of experiments, exhibited excellent gene disruption (up to 97%) and base substitution (up to 23%) without any apparent cytotoxicity. The addition of negative charges to the RNPs by complexing single-stranded oligonucleotide (ssON) significantly enhanced the delivery of both Cas9 and Cpf1 RNPs. The optimized formulation significantly suppressed both HBV DNA and covalently closed circular DNA (cccDNA) in HBV-infected human liver cells compared to adeno-associated virus type 2 (AAV2). These findings represent a significant contribution to the development of CRISPR/Cas RNP delivery technology and its practical applications in genome editing therapy.

DOI： 10.1016/j.jconrel.2020.12.013

Scopus

PubMed

Mohammad Enamul Hoque Kayesh, Michinori Kohara, Kyoko Tsukiyama-Kohara . Recent Insights Into the Molecular Mechanism of Toll-Like Receptor Response to Dengue Virus Infection. . Frontiers in microbiology12 744233 - 744233 2021Reviewed International journal

Language：English Publishing type：Research paper (scientific journal)

Dengue is the most prevalent and rapidly spreading mosquito-borne viral disease caused by dengue virus (DENV). Recently, DENV has been affecting humans within an expanding geographic range due to the warming of the earth. Innate immune responses play a significant role in antiviral defense, and Toll-like receptors (TLRs) are key regulators of innate immunity. Therefore, a detailed understanding of TLR and DENV interactions is important for devising therapeutic and preventive strategies. Several studies have indicated the ability of DENV to modulate the TLR signaling pathway and host immune response. Vaccination is considered one of the most successful medical interventions for preventing viral infections. However, only a partially protective dengue vaccine, the first licensed dengue vaccine CYD-TDV, is available in some dengue-endemic countries to protect against DENV infection. Therefore, the development of a fully protective, durable, and safe DENV vaccine is a priority for global health. Here, we demonstrate the progress made in our understanding of the host response to DENV infection, with a particular focus on TLR response and how DENV avoids the response toward establishing infection. We also discuss dengue vaccine candidates in late-stage development and the issues that must be overcome to enable their success.

DOI： 10.3389/fmicb.2021.744233

Scopus

PubMed

CD4, CD8b, and Cytokines Expression Profiles in Peripheral Blood Mononuclear Cells Infected with Different Subtypes of KoRV from Koalas (Phascolarctos cinereus) in a Japanese Zoo. . Viruses12 ( 12 ) 1415 2020.12

Mohammad Enamul Hoque Kayesh, Md Abul Hashem, Fumie Maetani, Taiki Eiei, Kyoya Mochizuki, Shinsaku Ochiai, Ayaka Ito, Nanao Ito, Hiroko Sakurai, Takayuki Asai, Kyoko Tsukiyama-Kohara . CD4, CD8b, and Cytokines Expression Profiles in Peripheral Blood Mononuclear Cells Infected with Different Subtypes of KoRV from Koalas (Phascolarctos cinereus) in a Japanese Zoo. . Viruses12 ( 12 ) 2020.12Reviewed International journal

Language：English Publishing type：Research paper (scientific journal)

Koala retrovirus (KoRV) poses a major threat to koala health and conservation, and currently has 10 identified subtypes: an endogenous subtype (KoRV-A) and nine exogenous subtypes (KoRV-B to KoRV-J). However, subtype-related variations in koala immune response to KoRV are uncharacterized. In this study, we investigated KoRV-related immunophenotypic changes in a captive koala population (Hirakawa zoo, Japan) with a range of subtype infection profiles (KoRV-A only vs. KoRV-A with KoRV-B and/or -C), based on qPCR measurements of CD4, CD8b, IL-6, IL-10 and IL-17A mRNA expression in unstimulated and concanavalin (Con)-A-stimulated peripheral blood mononuclear cells (PBMCs). Although CD4, CD8b, and IL-17A expression did not differ between KoRV subtype infection profiles, IL-6 expression was higher in koalas with exogenous infections (both KoRV-B and KoRV-C) than those with the endogenous subtype only. IL-10 expression did not significantly differ between subtype infection profiles but did show a marked increase-accompanying decreased CD4:CD8b ratio-in a koala with lymphoma and co-infected with KoRV-A and -B, thus suggesting immunosuppression. Taken together, the findings of this study provide insights into koala immune response to multiple KoRV subtypes, which can be exploited for the development of prophylactic and therapeutic interventions for this iconic marsupial species.

DOI： 10.3390/v12121415

Scopus

PubMed

Ezzikouri S, Nourlil J, Benjelloun S, Kohara M, Tsukiyama-Kohara K. . Coronavirus disease 2019-Historical context, virology, pathogenesis, immunotherapy, and vaccine development. . Hum Vaccin Immunother. 16 ( 12 ) 2992 - 3000 2020.12Invited Reviewed

Kayesh MEH, Amako Y, Hashem MA, Murakami S, Ogawa S, Yamamoto N, Hifumi T, Miyoshi N, Sugiyama M, Tanaka Y, Mizokami M, Kohara M, Tsukiyama-Kohara K. . Development of an in vivo delivery system for CRISPR/Cas9-mediated targeting of hepatitis B virus cccDNA . Virus Research290 198191 2020.12Reviewed

Sayeh Ezzikouri, Jalal Nourlil, Soumaya Benjelloun, Michinori Kohara, Kyoko Tsukiyama-Kohara . Coronavirus disease 2019-Historical context, virology, pathogenesis, immunotherapy, and vaccine development. . Human vaccines & immunotherapeutics16 ( 12 ) 2992 - 3000 2020.12Reviewed International journal

Language：English Publishing type：Research paper (scientific journal)

The current Coronavirus Disease 2019 (COVID-19) pandemic is causing great alarm around the world. The pathogen for COVID-19 - severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) - is the seventh known coronavirus to cause pneumonia in humans. While much remains unknown about SARS-CoV-2, physicians and researchers have begun to publish relevant findings, and much evidence is available on coronaviruses previously circulating in human and animal populations. In this review, we situate COVID-19 in its context as a transboundary viral disease, and provide a comprehensive discussion focused on the discovery, spread, virology, pathogenesis, and clinical features of this disease, its causative coronaviral pathogen, and approaches to combating the disease through immunotherapies and other treatments and vaccine development. An epidemiological survey revealed a potentially large number of asymptomatic SARS-CoV-2 carriers within the population, which may hamper efforts against COVID-19. Finally, we emphasize that vaccines against SARS-CoV-2, which may be developed by 2021, will be essential for prevention of COVID-19.

DOI： 10.1080/21645515.2020.1787068

Scopus

PubMed

　 PREV - NEXT 　

<Kyoko (Tsukiyama-)Kohara>

Papers - Kyoko (Tsukiyama-)Kohara