Faculty Profiles - Kyoko (Tsukiyama-)Kohara

Papers - Kyoko (Tsukiyama-)Kohara

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Uno Y, Ushirozako G, Uehara S, Murayama N, Fujiki Y, Kawaguchi H, Tsukiyama-Kohara K, Yamazaki H . Newly identified tree shrew cytochrome P450 2B6 (CYP2B6) and pig CYP2B6b are functional drug-metabolising enzymes. . Xenobiotica; the fate of foreign compounds in biological systems 1 - 10 2022.11Reviewed International journal

Kayesh MEH, Hashem MA, Maetani F, Goto A, Nagata N, Kasori A, Imanishi T, Tsukiyama-Kohara K . Molecular Insights into Innate Immune Response in Captive Koala Peripheral Blood Mononuclear Cells Co-Infected with Multiple Koala Retrovirus Subtypes. . Pathogens (Basel, Switzerland)11 ( 8 ) 2022.8Reviewed International journal

Characterization of host factors associated with the internal ribosomal entry sites of foot-and-mouth disease and classical swine fever viruses. . 12 ( 1 ) 6709 2022.4Reviewed International coauthorship

Kayesh MEH, Kohara M, Tsukiyama-Kohara K . An Overview of Recent Insights into the Response of TLR to SARS-CoV-2 Infection and the Potential of TLR Agonists as SARS-CoV-2 Vaccine Adjuvants. . Viruses13 ( 11 ) 2021.11Reviewed International journal

Kayesh MEH, Sanada T, Kohara M, Tsukiyama-Kohara K . Tree Shrew as an Emerging Small Animal Model for Human Viral Infection: A Recent Overview. . Viruses13 ( 8 ) 2021.8Reviewed International journal

Hashem MA, Kayesh MEH, Maetani F, Eiei T, Mochizuki K, Ochiai S, Ito A, Ito N, Sakurai H, Asai T, Tsukiyama-Kohara K . Koala retrovirus (KoRV) subtypes and their impact on captive koala (Phascolarctos cinereus) health. . Archives of virology166 ( 7 ) 1893 - 1901 2021.7Reviewed International journal

Makoto Saito1,*, Yasushi Itoh2,*, Fumihiko Yasui1,*, Tsubasa Munakata1, Daisuke Yamane1, Makoto Ozawa3, Risa Ito4, Takayuki Katoh4, Hirohito Ishigaki2, Misako Nakayama2, Shintaro Shichinohe2, Kenzaburo Yamaji1, Naoki Yamamoto1, Ai Ikejiri1, Tomoko Honda1, Takahiro Sanada1, Yoshihiro Sakoda5, Hiroshi Kida6, Le Thi Quynh Mai7, Yoshihiro Kawaoka8, Kazumasa Ogasawara2, Kyoko Tsukiyama-Kohara3,†, Hiroaki Suga4,†, and Michinori Kohara . Targeted macrocycles hamper hemagglutinin adsorption and fusion, and have antiviral effects in murine and macaque models of influenza . Nature Communications12 ( 1 ) 2654 2021.5Reviewed International coauthorship

Abounouh K. . Blocking neddylation elicits antiviral effect against hepatitis B virus replication . Molecular Biology Reports 2021Reviewed International journal

Takagi A, Amako Y, Yamane D, Kitab B, Tokunaga Y, El-Gohary A, Kohara M, Tsukiyama-Kohara K . Longer Poly(U) Stretches in the 3'UTR Are Essential for Replication of the Hepatitis C Virus Genotype 4a Clone in <i>in vitro</i> and <i>in vivo</i>. . Frontiers in microbiology12 764816 2021Reviewed International journal

Kayesh M.E.H. . Mammalian animal models for dengue virus infection: a recent overview . Archives of Virology167 ( 1 ) 31 - 44 2021Reviewed International journal

Mohammad Enamul Hoque Kayesh, Michinori Kohara, Kyoko Tsukiyama-Kohara . Toll-like Receptor Response to Human Immunodeficiency Virus Type 1 or Co-Infection with Hepatitis B or C Virus: An Overview. . International journal of molecular sciences24 ( 11 ) 2023.6Reviewed International journal

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

Toll-like receptors (TLRs) are evolutionarily conserved pattern recognition receptors that play important roles in the early detection of pathogen-associated molecular patterns and shaping innate and adaptive immune responses, which may influence the consequences of infection. Similarly to other viral infections, human immunodeficiency virus type 1 (HIV-1) also modulates the host TLR response; therefore, a proper understanding of the response induced by human HIV-1 or co-infection with hepatitis B virus (HBV) or hepatitis C virus (HCV), due to the common mode of transmission of these viruses, is essential for understanding HIV-1 pathogenesis during mono- or co-infection with HBV or HCV, as well as for HIV-1 cure strategies. In this review, we discuss the host TLR response during HIV-1 infection and the innate immune evasion mechanisms adopted by HIV-1 for infection establishment. We also examine changes in the host TLR response during HIV-1 co-infection with HBV or HCV; however, this type of study is extremely scarce. Moreover, we discuss studies investigating TLR agonists as latency-reverting agents and immune stimulators towards new strategies for curing HIV. This understanding will help develop a new strategy for curing HIV-1 mono-infection or co-infection with HBV or HCV.

DOI： 10.3390/ijms24119624

PubMed

Mohammad Enamul Hoque Kayesh, Md Abul Hashem, Takahiro Sanada, Bouchra Kitab, Md Haroon Or Rashid, Lipi Akter, Sayeh Ezzikouri, Shuko Murakami, Shintaro Ogawa, Yasuhito Tanaka, Michinori Kohara and Kyoko Tsukiyama-Kohara . Characterization of innate immune response to hepatitis B virus genotype F acute infection in tree shrew (Tupaia belangeri) model . Frontiers in Virology2 926831 2022.8Reviewed International coauthorship International journal

Authorship：Corresponding author Language：English Publishing type：Research paper (scientific journal) Publisher：Frontiers Media SA

Hepatitis B virus (HBV) infection is a global public health problem. The clinical outcomes of HBV infections are influenced by host as well as viral factors, including viral genotypes and subgenotypes. The interplay between HBV and host innate immunity remains unclear because of the lack of a suitable small animal model. Tree shrews (Tupaia belangeri) have been utilized as a useful animal model for hepatitis viruses such as hepatitis B and C viruses. In this study, we characterized acute infections by HBV genotype F (HBV-F) wild type (Wt) and mutant type (Mt) viruses in adult tree shrews. Serum alanine aminotransferase levels were measured before and post- infection 7 and 14 dpi. Both HBV-F-Wt and Mt were detected in the HBV-F-infected tree shrew serum and liver tissue at 7 and 14 dpi. We examined the intrahepatic expression patterns of Toll-like receptors (TLRs) (TLR1–9 mRNAs), cGAS, several transcription factors such as STAT1, STAT2, IRF7, HNF4, PD-L1, and cytokines, including IFN-β, IFN-γ, IL-6, and TNF-α in HBV-F Wt/Mt-infected tree shrews. When compared with uninfected animal group, significant suppression of TLR8 in HBV-F-Wt infected animals and significant suppression of PD-L1 in both HBV-F-Wt and Mt infected animals were observed. Thus, tree shrew can be a useful animal model to characterize HBV-F pathogenesis.

DOI： 10.3389/fviro.2022.926831

Md Abul Hashem, Mohammad Enamul Hoque Kayesh, Fumie Maetani, Atsushi Goto, Noriko Nagata, Aki Kasori, Tetsuya Imanishi, Kyoko Tsukiyama-Kohara . Subtype distribution and expression of the koala retrovirus in the Japanese zoo koala population. . Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases102 105297 - 105297 2022.8Reviewed International journal

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

We investigated the proviral copies and RNA expression in koala retrovirus (KoRV)-infected koalas. To ascertain any variation in viral load by institution, age, sex, or body condition score, we quantified KoRV proviral DNA and RNA loads in captive koalas (n = 37) reared in Japanese zoos. All koalas were positive for KoRV genes (pol, LTRs, and env of KoRV-A) in genomic DNA (gDNA), and 91.89% were positive for the pol gene in RNA. In contrast, the distribution rates of KoRV-B, KoRV-C, KoRV-D, and KoRV-F env genes in gDNA were 94.59%, 27.03%, 67.57%, and 54.05%, respectively. A wide inter-individual variation and/or a significant inter-institutional difference in proviral DNA (p < 0.0001) and RNA (p < 0.001) amounts (copies/103 koala β-actin copies) were observed in Awaji Farm England Hill Zoo koalas, which were obtained from southern koala populations, suggesting exogenous incorporation of KoRV in these koalas. Significant (p < 0.05) age differences were noted in KoRV RNA load (p < 0.05) and median total RNA load (p < 0.001), with loads higher in younger koalas (joeys and juveniles). Thus, the current study provides the distribution of KoRV subtypes in Japanese zoo koala populations and identifies several additional risk factors (sex, age, and body condition) associated with KoRV expression.

DOI： 10.1016/j.meegid.2022.105297

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Reverse vaccinology-based prediction of a multi-epitope SARS-CoV-2 vaccine and its tailoring to new coronavirus variants. . 2022.5Reviewed International coauthorship

Kayesh MEH, Kohara M, Tsukiyama-Kohara K. . Toll-like Receptor Response to Hepatitis C Virus Infection: A Recent Overview. . Int J Mol Sci.23 ( 10 ) 5475 2022.5Reviewed International coauthorship

Mohammad Enamul Hoque Kayesh, Michinori Kohara, Kyoko Tsukiyama-Kohara . Toll-like Receptor Response to Hepatitis C Virus Infection: A Recent Overview. . International journal of molecular sciences23 ( 10 ) 2022.5Reviewed International journal

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

Hepatitis C virus (HCV) infection remains a major global health burden, causing chronic hepatitis, cirrhosis, and hepatocellular carcinoma. Toll-like receptors (TLRs) are evolutionarily conserved pattern recognition receptors that detect pathogen-associated molecular patterns and activate downstream signaling to induce proinflammatory cytokine and chemokine production. An increasing number of studies have suggested the importance of TLR responses in the outcome of HCV infection. However, the exact role of innate immune responses, including TLR response, in controlling chronic HCV infection remains to be established. A proper understanding of the TLR response in HCV infection is essential for devising new therapeutic approaches against HCV infection. In this review, we discuss the progress made in our understanding of the host innate immune response to HCV infection, with a particular focus on the TLR response. In addition, we discuss the mechanisms adopted by HCV to avoid immune surveillance mediated by TLRs.

DOI： 10.3390/ijms23105475

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Wahiba Ezzemani, Anass Kettani, Subrahmanyam Sappati, Kavya Kondaka, Hicham El Ossmani, Kyoko Tsukiyama-Kohara, Haya Altawalah, Rachid Saile, Michinori Kohara, Soumaya Benjelloun, Sayeh Ezzikouri . Reverse vaccinology-based prediction of a multi-epitope SARS-CoV-2 vaccine and its tailoring to new coronavirus variants. . Journal of biomolecular structure & dynamics 1 - 22 2022.5Reviewed International journal

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

The genome feature of SARS-CoV-2 leads the virus to mutate and creates new variants of concern. Tackling viral mutations is also an important challenge for the development of a new vaccine. Accordingly, in the present study, we undertook to identify B- and T-cell epitopes with immunogenic potential for eliciting responses to SARS-CoV-2, using computational approaches and its tailoring to coronavirus variants. A total of 47 novel epitopes were identified as immunogenic triggering immune responses and no toxic after investigation with in silico tools. Furthermore, we found these peptide vaccine candidates showed a significant binding affinity for MHC I and MHC II alleles in molecular docking investigations. We consider them to be promising targets for developing peptide-based vaccines against SARS-CoV-2. Subsequently, we designed two efficient multi-epitopes vaccines against the SARS-CoV-2, the first one based on potent MHC class I and class II T-cell epitopes of S (FPNITNLCPF-NYNYLYRLFR-MFVFLVLLPLVSSQC), M (MWLSYFIASF-GLMWLSYFIASFRLF), E (LTALRLCAY-LLFLAFVVFLLVTLA), and N (SPRWYFYYL-AQFAPSASAFFGMSR). The second candidate is the result of the tailoring of the first designed vaccine according to three classes of SARS-CoV-2 variants. Molecular docking showed that the protein-protein binding interactions between the vaccines construct and TLR2-TLR4 immune receptors are stable complexes. These findings confirmed that the final multi-epitope vaccine could be easily adapted to new viral variants. Our study offers a shortlist of promising epitopes that can accelerate the development of an effective and safe vaccine against the virus and its adaptation to new variants.Communicated by Ramaswamy H. Sarma.

DOI： 10.1080/07391102.2022.2075468

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PubMed

Hashem MA, Kayesh MEH, Maetani F, Goto A, Nagata N, Kasori A, Imanishi T, Tsukiyama-Kohara K . Subtype distribution and expression of the koala retrovirus in the Japanese zoo koala population. . Infect Genet Evol. 105297 2022.5Reviewed International coauthorship

Yutaro Ide, Bouchra Kitab, Nobumasa Ito, Riai Okamoto, Yui Tamura, Takafumi Matsui, Yoshihiro Sakoda, Kyoko Tsukiyama-Kohara . Characterization of host factors associated with the internal ribosomal entry sites of foot-and-mouth disease and classical swine fever viruses. . Scientific reports12 ( 1 ) 6709 - 6709 2022.4Reviewed International journal

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

Foot-and-mouth disease virus (FMDV) and classical swine fever virus (CSFV) possess positive-sense single-stranded RNA genomes and an internal ribosomal entry site (IRES) element within their 5'-untranslated regions. To investigate the common host factors associated with these IRESs, we established cell lines expressing a bicistronic luciferase reporter plasmid containing an FMDV-IRES or CSFV-IRES element between the Renilla and firefly luciferase genes. First, we treated FMDV-IRES cells with the French maritime pine extract, Pycnogenol (PYC), and examined its suppressive effect on FMDV-IRES activity, as PYC has been reported to have antiviral properties. Next, we performed microarray analysis to identify the host factors that modified their expression upon treatment with PYC, and confirmed their function using specific siRNAs. We found that polycystic kidney disease 1-like 3 (PKD1L3) and ubiquitin-specific peptidase 31 (USP31) were associated with FMDV-IRES activity. Moreover, silencing of these factors significantly suppressed CSFV-IRES activity. Thus, PKD1L3 and USP31 are host factors associated with the functions of FMDV- and CSFV-IRES elements.

DOI： 10.1038/s41598-022-10437-z

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Mohammad Enamul Hoque Kayesh, Md Abul Hashem, Michinori Kohara, Kyoko Tsukiyama-Kohara . In vivo Delivery Tools for Clustered Regularly Interspaced Short Palindromic Repeat/Associated Protein 9-Mediated Inhibition of Hepatitis B Virus Infection: An Update. . Frontiers in microbiology13 953218 - 953218 2022Reviewed International journal

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

Chronic hepatitis B virus (HBV) infection remains a major global health problem despite the availability of an effective prophylactic HBV vaccine. Current antiviral therapies are unable to fully cure chronic hepatitis B (CHB) because of the persistent nature of covalently closed circular DNA (cccDNA), a replicative template for HBV, which necessitates the development of alternative therapeutic approaches. The CRISPR/Cas system, a newly emerging genome editing tool, holds great promise for genome editing and gene therapy. Several in vitro and/or in vivo studies have demonstrated the effectiveness of HBV-specific clustered regularly interspaced short palindromic repeat (CRISPR)/associated protein 9 (CRISPR/Cas9) systems in cleaving HBV DNA and cccDNA. Although recent advances in CRISPR/Cas technology enhance its prospects for clinical application against HBV infection, in vivo delivery of the CRISPR/Cas9 system at targets sites remains a major challenge that needs to be resolved before its clinical application in gene therapy for CHB. In the present review, we discuss CRISPR/Cas9 delivery tools for targeting HBV infection, with a focus on the development of adeno-associated virus vectors and lipid nanoparticle (LNP)-based CRISPR/Cas ribonucleoprotein (RNP) delivery to treat CHB. In addition, we discuss the importance of delivery tools in the enhancement of the antiviral efficacy of CRISPR/Cas9 against HBV infection.

DOI： 10.3389/fmicb.2022.953218

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PubMed

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Papers - Kyoko (Tsukiyama-)Kohara