Article
Virology
Ranran Wang, June F. Yang, Taylor E. Senay, Wei Liu, Jianxin You
Summary: Merkel cell carcinoma (MCC) is a lethal skin cancer that has increased in incidence in recent years. Merkel cell polyomavirus (MCPyV) is associated with a majority of MCC cases. In this study, the researchers found that MCPyV infection induces the expression of interferons (IFNs) and IFN-stimulated genes (ISGs) in human dermal fibroblasts (HDFs), but the IFN-mediated induction of ISGs is not crucial for viral control. Instead, type I IFN directly represses viral transcription. The researchers also found that growth factors induced by skin abrasion or UV irradiation can stimulate MCPyV gene expression and replication, supporting persistent infection.
JOURNAL OF VIROLOGY
(2023)
Article
Medicine, General & Internal
Danielle Brazel, Priyanka Kumar, Hung Doan, Tianyu Pan, Weining Shen, Ling Gao, Justin T. Moyers
Summary: Merkel cell carcinoma (MCC) is a rare and aggressive skin cancer with increasing incidence. This study aimed to identify actionable alterations associated with tumor mutation burden (TMB) using the OncoKB database. The findings suggest that targeted therapies may be a viable treatment option for selected MCC patients.
Review
Biochemistry & Molecular Biology
John Charles Rotondo, Chiara Mazziotta, Carmen Lanzillotti, Mauro Tognon, Fernanda Martini
Summary: This review discusses the impact of epigenetic mechanisms on Merkel cell polyomavirus (MCPyV)-driven Merkel Cell Carcinoma (MCC), highlighting the importance of histone posttranslational modifications, DNA methylation, and microRNA regulation. The dysregulation of these epigenetic processes may have clinical significance for MCC diagnosis, prognosis, and therapy.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Biochemistry & Molecular Biology
Elena Dellambra, Maria Luigia Carbone, Francesca Ricci, Francesco Ricci, Francesca Romana Di Pietro, Gaia Moretta, Sofia Verkoskaia, Elisa Feudi, Cristina M. Failla, Damiano Abeni, Luca Fania
Summary: Merkel cell carcinoma (MCC) is a rare and highly aggressive neuroendocrine carcinoma of the skin, with increasing incidence worldwide. Treatment of advanced MCC tumors with immune checkpoint inhibitors has shown effective results, highlighting the importance of immunotherapy in managing this disease.
Review
Oncology
Steffi Silling, Alexander Kreuter, Thilo Gambichler, Thomas Meyer, Eggert Stockfleth, Ulrike Wieland
Summary: Merkel cell polyomavirus (MCPyV) is a common virus on human skin, leading to the development of a rare but aggressive Merkel cell carcinoma (MCC) in older individuals, especially those with fair skin, male sex, and immunosuppression. The incidence of MCC, caused by MCPyV or UV damage, is increasing globally, with risk factors including male sex, older age, fair skin, intense UV exposure, and immunosuppression. Early diagnosis and prompt treatment are crucial for reducing MCC morbidity and mortality.
Review
Oncology
Roland Houben, Bueke Celikdemir, Thibault Kervarrec, David Schrama
Summary: By studying the cancer-inducing ability of polyomaviruses, researchers have made significant progress in understanding tumor suppressor proteins and have identified Merkel cell polyomavirus (MCPyV) as a human polyomavirus-induced cancer. Intensive research has since uncovered many details about the virus-host interaction and the molecular mechanisms by which MCPyV causes cancer. This review summarizes the current knowledge on MCPyV and MCC and discusses remaining questions.
Article
Virology
Nathan A. Krump, Ranran Wang, Wei Liu, June F. Yang, Tongcui Ma, Jianxin You
Summary: MCPyV, which can cause Merkel cell carcinoma, infects most humans asymptomatically. Understanding MCPyV biology and its interaction with host immune response may help develop targeted therapies for MCC. MCPyV replication induces an innate immune response, involving cGAS-STING, NF-kappa B, and IFI16 pathways.
JOURNAL OF VIROLOGY
(2021)
Article
Medicine, Research & Experimental
Monique E. Verhaegen, Paul W. Harms, Julia J. Van Goor, Jacob Arche, Matthew T. Patrick, Dawn Wilbert, Haley Zabawa, Marina Grachtchouk, Chia-Jen Liu, Kevin Hu, Michael C. Kelly, Ping Chen, Thomas L. Saunders, Stephan Weidinger, Li-Jyun Syu, John S. Runge, Johann E. Gudjonsson, Sunny Y. Wong, Isaac Brownell, Marcin Cieslik, Aaron M. Udager, Arul M. Chinnaiyan, Lam C. Tsoi, Andrzej A. Dlugosz
Summary: Merkel cell carcinoma (MCC) is an aggressive skin cancer that expresses specific genes similar to skin-resident Merkel cells. Researchers have used ATOH1 to induce MCC development in mice by cellular reprogramming. By conditionally expressing MCPyV TAgs and ATOH1 in mouse epidermal cells, they were able to generate MCC-like tumor cells from hair follicles. The study confirmed the similarity between mouse and human MCCs and revealed that loss of p53 is necessary for the progression of MCC in this mouse model.
JOURNAL OF CLINICAL INVESTIGATION
(2022)
Article
Multidisciplinary Sciences
Steven D. Forsythe, Richard A. Erali, Preston Laney, Hemamylammal Sivakumar, Wencheng Li, Aleksander Skardal, Shay Soker, Konstantinos Votanopoulos
Summary: This study explores the application of patient tumor organoids (PTOs) in modeling personalized research in Merkel cell carcinoma (MCC). PTOs and immune enhanced organoids (iPTOs) were established from surgical specimens and treated with chemotherapy or immunotherapy agents. Results showed chemotherapy efficacy in some specimens while immunotherapy was not effective. Resistance to pembrolizumab correlated with the corresponding patient's treatment response. The study demonstrates the feasibility of establishing and immune enhancing MCC PTOs for personalized research and exploration of treatment regimens in the preclinical setting.
SCIENTIFIC REPORTS
(2022)
Article
Biochemistry & Molecular Biology
Nathan Lanclos, Peter Radulovic, Jackson Bland, Valentin Oganisyan, Kelton Radefeld, Vladimir N. Uversky
Summary: This study computationally characterizes the intrinsic disorder within the MCPyV proteome and suggests mechanisms that contribute to the oncogenicity of the virus. The findings indicate that MCPyV may use disorder and phase condensation to alter viral function, emphasizing the potential role of disorder in the virus's life cycle and the development of novel therapeutic agents.
JOURNAL OF CELLULAR BIOCHEMISTRY
(2023)
Article
Dermatology
J. H. Wu, A. L. Limmer, D. Narayanan, H. Q. Doan, R. A. Simonette, P. L. Rady, S. K. Tyring
Summary: The study demonstrates that AKT has important regulatory functions in Merkel cell carcinoma cells, and inhibition of AKT has significant inhibitory effects on MCC cell proliferation by affecting proliferative pathways.
CLINICAL AND EXPERIMENTAL DERMATOLOGY
(2021)
Review
Microbiology
Nathan A. Krump, Jianxin You
Summary: MCPyV infection is common in the skin and can lead to MCC, with potential for prophylactic and targeted intervention. Understanding host responses to control MCPyV infection could inform preventive measures, while vulnerabilities in MCC associated with MCPyV could provide insights for potential solutions. The study proposes a model where inadequate restriction of MCPyV infection in aging and chronically UV-damaged skin may contribute to MCC tumorigenesis.
FRONTIERS IN MICROBIOLOGY
(2021)
Article
Cell Biology
Thibault Kervarrec, Silke Appenzeller, Anne Tallet, Marie-Laure Jullie, Pierre Sohier, Francois Guillonneau, Arno Rutten, Patricia Berthon, Yannick Le Corre, Ewa Hainaut-Wierzbicka, Astrid Blom, Nathalie Beneton, Guido Bens, Charline Nardin, Francois Aubin, Monica Dinulescu, Sebastien Visee, Michael Herfs, Antoine Touze, Serge Guyetant, Mahtab Samimi, Roland Houben, David Schrama
Summary: This study found that wildtype MCPyV genomes and VP1 transcription exist in a subset of MCC.
Article
Virology
Bizunesh Abere, Hongzhao Zhou, Masahiro Shuda, Donna B. Stolz, Kyle Rapchak, Patrick S. Moore, Yuan Chang
Summary: We report a new recombinase-mediated MCV minicircle (MCVmc) system that allows for easy genetic manipulation and characterization of viral gene expression kinetics during MCV replication. Our findings reveal that MCV has multiple self-encoded viral restriction mechanisms to promote viral latency over lytic replication.
Article
Biochemistry & Molecular Biology
Luz E. Ortiz, Alexander M. Pham, Hyun Jin Kwun
Summary: MCPyV's LT antigen interacts with E3 ligases to limit viral replication, and Lys 585 residue in LT is identified as the ubiquitin conjugation site, impacting MCPyV genome replication.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Multidisciplinary Sciences
Thachawech Kimprasit, Mitsuo Nunome, Keisuke Iida, Yoshitaka Murakami, Min-Liang Wong, Chung-Hsin Wu, Ryosuke Kobayashi, Yupadee Hengjan, Hitoshi Takemae, Kenzo Yonemitsu, Ryusei Kuwata, Hiroshi Shimoda, Lifan Si, Joon-Hyuk Sohn, Susumu Asakawa, Kenji Ichiyanagi, Ken Maeda, Hong-Shik Oh, Tetsuya Mizutani, Junpei Kimura, Atsuo Iida, Eiichi Hondo
Summary: The study examined the role of the eastern bent-winged bat in the dispersion of bat adenovirus and bat alphacoronavirus in East Asia, based on gene flow and divergence times using fecal guano samples. The findings suggest that the host mitochondrial DNA phylogenies were not significantly congruent with those of the viruses, indicating the bats serve as important natural reservoirs of the viruses.
Article
Multidisciplinary Sciences
Shiho Ando, Yuki Matsuzawa, Hiromichi Tsurui, Tetsuya Mizutani, Damien Hall, Yutaka Kuroda
Summary: After months of lockdown, finding a balance between reopening society and implementing non-pharmaceutical measures to reduce interpersonal contacts is crucial. A stochastic model presented in this study evaluates the potential for second-wave infection outbreaks based on timing, extent, and pattern of lockdown relaxation strategies. Results show that a full lockdown leads to the lowest number of infections, but high personal mobility or inadequate detection/quarantine capacity can increase infections. Taking action to reduce viral transmission probability, such as through social distancing or mask-wearing, can be as effective as a soft lockdown.
SCIENTIFIC REPORTS
(2021)
Article
Infectious Diseases
Montira Yossapol, Miku Yamamoto, Michiyo Sugiyama, Justice Opare Odoi, Tsutomu Omatsu, Tetsuya Mizutani, Kenji Ohya, Tetsuo Asai
Summary: The study isolated CTX-M-14-producing Escherichia coli from Siberian weasels and domestic animals on a veterinary campus, showing a potential association between antimicrobial resistance in wild and domestic animals. The ESBL-producing E. coli from both sources were found to share genetic similarities, suggesting a common origin of antimicrobial resistance.
Article
Biochemistry & Molecular Biology
Mami Oba, Wen Rongduo, Akatsuki Saito, Tamaki Okabayashi, Tomoko Yokota, Junko Yasuoka, Yoko Sato, Koji Nishifuji, Hitoshi Wake, Yutaka Nibu, Tetsuya Mizutani
Summary: The study demonstrated that a protease present in natto extract inhibits SARS-CoV-2 and BHV-1 infection by degrading viral proteins. However, heat treatment of the natto extract reverses this inhibitory effect.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2021)
Article
Virology
Liudmila N. Yashina, Sergey A. Abramov, Alexander Zhigalin, Natalia A. Smetannikova, Tamara A. Dupal, Anton Krivopalov, Fuka Kikuchi, Kae Senoo, Satoru Arai, Tetsuya Mizutani, Motoi Suzuki, Joseph A. Cook, Richard Yanagihara
Summary: The discovery of genetically distinct hantaviruses in multiple species of shrews, moles and bats reveals a complex evolutionary history involving cross-species transmission. Different viruses, such as SWSV, ALTV, LENV, and ALTV-related viruses, have been found in various shrew species in different regions, suggesting a diverse and geographically widespread distribution pattern. These findings hint at the emergence of new hantavirus species through ancient cross-species transmission and subsequent diversification within Sorex shrews in Eurasia.
Article
Virology
Fuka Kikuchi, Kae Senoo, Satoru Arai, Kimiyuki Tsuchiya, Nguyen Truong Son, Masaharu Motokawa, Marie Ranorosoa, Saw Bawm, Kyaw Lin, Hitoshi Suzuki, Akira Unno, Keisuke Nakata, Masashi Harada, Keiko Tanaka-Taya, Shigeru Morikawa, Motoi Suzuki, Tetsuya Mizutani, Richard Yanagihara
Summary: Hantaviruses harbored by various small mammal species in Japan, Vietnam, Myanmar, and Madagascar were analyzed for virus-host relationships and geographic distribution, revealing the presence of different strains in different rodent species and evidence of host-switching through co-phylogeny mapping.
Article
Biochemistry & Molecular Biology
Mohamed Elbadawy, Yuki Kato, Nagisa Saito, Kimika Hayashi, Amira Abugomaa, Mio Kobayashi, Toshinori Yoshida, Makoto Shibutani, Masahiro Kaneda, Hideyuki Yamawaki, Tetsuya Mizutani, Chang-Kweng Lim, Masayuki Saijo, Kazuaki Sasaki, Tatsuya Usui, Tsutomu Omatsu
Summary: This study established and characterized intestinal organoids from Leschenault's rousette bat, which showed susceptibility to Pteropine orthoreovirus (PRV) but not to SARS-CoV-2 in experimental inoculation. This organoid model provides a useful tool for understanding the tolerance mechanisms of emerging bat-associated viruses such as Ebola and Marburg virus.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Veterinary Sciences
Rongduo Wen, Hideharu Ochiai, Jumpei Uchiyama, Nanako Osawa, Mami Oba, Yukie Katayama, Kaixin Li, Tsutomu Omatsu, Kenichi Tamukai, Kaoru Suzuki, Hiroo Madarame, Shinji Makino, Tetsuya Mizutani
Summary: The study revealed that African hedgehog adenovirus uses the p38 pathway for replication in infected cells and induces cytopathic effects. Inhibitors of the p38 pathway were effective in suppressing viral replication, but did not inhibit virus-induced cytopathic effects.
RESEARCH IN VETERINARY SCIENCE
(2021)
Article
Infectious Diseases
Satoko Sugimoto, Yuto Suda, Noriyo Nagata, Shuetsu Fukushi, Tomoki Yoshikawa, Takeshi Kurosu, Tetsuya Mizutani, Masayuki Saijo, Masayuki Shimojima
Summary: Keterah orthonairovirus can replicate in various cell lines and cause severe liver lesions and death in IFNAR-/- mice. Serum transfusion after infection can delay the time to death in IFNAR-/- mice.
TICKS AND TICK-BORNE DISEASES
(2022)
Editorial Material
Cell Biology
Michiyo Kataoka, Tetsuya Tsukamoto, Yasuhisa Tajima, Yuko Sato, Harutaka Katano, Tadaki Suzuki, Noriko Nakajima
Article
Virology
Yuichiro Hirata, Harutaka Katano, Shun Iida, Sohtaro Mine, Sayaka Nagasawa, Yohsuke Makino, Ayumi Motomura, Seiya Ozono, Yuko Sato, Tsuyoshi Sekizuka, Makoto Kuroda, Rutsuko Yamaguchi, Go Inokuchi, Suguru Torimitsu, Shinji Akitomi, Daisuke Yajima, Hisako Saitoh, Tadaki Suzuki, Hirotaro Iwase
Summary: This study conducted genomic analyses of SARS-CoV-2 in 18 forensic autopsy cases and identified the distribution of the virus primarily in the respiratory organs. In one case of death due to COVID-19, intrahost genomic diversity of the virus was found. The study suggests the feasibility of genomic analysis in forensic autopsy cases and the potential for uncovering important information in COVID-19 deaths.
JOURNAL OF MEDICAL VIROLOGY
(2023)
Article
Veterinary Sciences
Junro Hayasaka, Yuka Nunomura, Miki Omura, Yukie Katayama, Tomoko Yokota, Nanako Osawa, Shinji Makino, Tetsuya Mizutani, Tsuyoshi Uchide, Yoshiteru Murata
Summary: The study showed that long-term administration of Lactobacillus probiotics significantly increased the count of regulatory T cells in dogs, but cessation of administration may lead to a decrease. Additionally, plasma IgA levels tended to increase after stopping Lactobacillus administration.
JAPANESE JOURNAL OF VETERINARY RESEARCH
(2021)
Article
Veterinary Sciences
Atsuo Iida, Hitoshi Takemae, Ronald Tarigan, Ryosuke Kobayashi, Hirokazu Kato, Hiroshi Shimoda, Tsutomu Omatsu, Supratikno, Chaerul Basri, Ni Luh Putu Ika Mayasari, Srihadi Agungpriyono, Ken Maeda, Tetsuya Mizutani, Eiichi Hondo
Summary: The study identified plant viral homologous sequences in the liver tissue of large flying foxes from Indonesia, suggesting that bats may be potential carriers or vectors of plant viruses. Evidence of viral endogenization into the host genome was provided, offering novel perspectives on viral invasion, variation, and host interaction in wild animals.
JOURNAL OF VETERINARY MEDICAL SCIENCE
(2021)
Article
Veterinary Sciences
Rie Doi, Mami Oba, Tetsuya Mizutani
Summary: This study evaluated the activity of phytohormonal herbicides against Sarcocystis bradyzoites, showing that some of the herbicides caused mortality of Sarcocystis cruzi bradyzoites and induced morphological changes.
JAPANESE JOURNAL OF VETERINARY RESEARCH
(2021)
Meeting Abstract
Oncology
Tetsuya Mizutani, Hideaki Tsuyoshi, Shizuka Yamada, Yoshio Yoshida
