Correction
Multidisciplinary Sciences
Rosamaria Pennisi, Maria Musarra-Pizzo, Zhixiang Lei, Grace Guoying Zhou, Maria Teresa Sciortino
Summary: The paper has been amended and the revised version can be accessed through a link at the top of the paper.
SCIENTIFIC REPORTS
(2021)
Article
Cell Biology
Robert J. J. Jansens, Ruth Verhamme, Aashiq H. Mirza, Anthony Olarerin-George, Cliff Van Waesberghe, Samie R. Jaffrey, Herman W. Favoreel
Summary: Chemical modifications of mRNA, such as N6-methyladenosine (m6A), play a role in post-transcriptional gene regulation. This study found that alphaherpesvirus kinases can trigger phosphorylation of components of the m6A methyltransferase complex, leading to its inhibition and a decrease in m6A levels in virus-infected cells. The viral US3 protein is responsible for this phosphorylation and inhibition, and while inactivation of the m6A methyltransferase complex is not necessary for virus replication, the m6A methylation motif is underrepresented in alphaherpesvirus genomes.
Article
Microbiology
Yifei Liao, Blanca Lupiani, Mohammad AI-Mahmood, Sanjay M. Reddy
Summary: Marek's disease virus (MDV) is a potent oncogenic alphaherpesvirus that causes T-cell lymphomas in chickens. The U(S)3 protein kinase of MDV plays a crucial role in virus replication and pathogenicity. This study identified novel substrates for U(S)3 and characterized its impact on MDV pathogenesis.
Article
Immunology
Shuyong Zhu, Abel Viejo-Borbolla
Summary: HSV-1 and HSV-2 are two of the most prevalent human viruses worldwide, causing a variety of diseases. Immune responses play a key role in controlling HSV, but the virus has developed mechanisms to evade them. The severity of disease upon HSV infection varies among individuals, partly due to genetic polymorphisms. HSV has lytic and latent replication cycles, with the latter leading to disease.
Article
Virology
Michiel van Gent, Jessica J. Chiang, Santoshi Muppala, Cindy Chiang, Walid Azab, Lisa Kattenhorn, David M. Knipe, Nikolaus Osterrieder, Michaela U. Gack
Summary: Recent studies show that herpes simplex virus 1 (HSV-1) can evade the immune response by phosphorylating the cytosolic pathogen sensor RIG-I, keeping it in a signaling-repressed state.
JOURNAL OF VIROLOGY
(2022)
Review
Virology
Hemant Borase, Deepak Shukla
Summary: This review summarizes the pathogenesis of HSV-2 and its cellular interactions, explores new strategies and challenges in regulating HSV-2 replication and influencing the cell cycle through host cellular components, and presents a fresh perspective on the treatment of HSV-2 by targeting cellular proteins and pathways.
Article
Pharmacology & Pharmacy
Etienne E. Muller, Dumisile Maseko, Ranmini S. Kularatne
Summary: This study conducted phenotypic and genotypic surveillance on ACV resistance in HSV-2 derived from genital ulcer samples collected in a primary healthcare facility in South Africa. The results revealed no resistance-associated mutations, but identified several known natural polymorphisms and amino acid changes of unknown significance. All cultivable HSV-2 isolates showed susceptibility to ACV.
ANTIVIRAL RESEARCH
(2022)
Article
Genetics & Heredity
Xiuye Wang, Liang Liu, Adam W. Whisnant, Thomas Hennig, Lara Djakovic, Nabila Haque, Cindy Bach, Rozanne M. Sandri-Goldin, Florian Erhard, Caroline C. Friedel, Lars Dolken, Yongsheng Shi
Summary: This study reveals that HSV-1 infection causes widespread changes in host mRNA APA with the involvement of ICP27, leading to intronic polyadenylation and early termination of RNAPII. These changes contribute to altered gene expression patterns and the expression of truncated mRNAs, suggesting a multi-faceted host response to viral infection and cellular stress.
Article
Immunology
Marzena Lenart, Edyta Dzialo, Anna Kluczewska, Kazimierz Weglarczyk, Anna Szaflarska, Magdalena Rutkowska-Zapala, Marcin Surmiak, Marek Sanak, Anna Pituch-Noworolska, Maciej Siedlar
Summary: The study identified upregulated expression of four miRNAs in patients with severe and/or recurrent HSV infection, which, when inhibited, affected NK cell antiviral response. Furthermore, these miRNAs were found to regulate genes involved in antiviral response pathways and impact NK cell intracellular protein expression.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Pathology
Melissa Krystel-Whittemore, May P. Chan, Sara C. Shalin, Kenan J. Sauder, Amy Hudson, Ruth K. Foreman, Mai P. Hoang, Jeoffry B. Brennick, Shaofeng Yan, Rosalynn M. Nazarian
Summary: This study presents the first known report of herpes virus infecting deep stromal cells of the dermis, highlighting the importance of considering cutaneous stromal herpes in patients with atypical clinical lesions, especially when immunocompromised. Establishing the correct diagnosis is crucial for initiating therapy.
AMERICAN JOURNAL OF SURGICAL PATHOLOGY
(2021)
Article
Immunology
Meng-Shan Tsai, Shun-Hua Chen, Chih-Peng Chang, Yi-Ling Hsiao, Li-Chiu Wang
Summary: ILK reduces the accumulation of H3K9me3 on HSV-1 DNA by reducing SUV39H1 and TRIM28 binding, enhancing virus replication. ILK knockdown decreases TRIM28 phosphorylation, weakening its inhibition on lytic gene transcription. ILK inhibitor suppresses HSV-1 replication.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2022)
Article
Dermatology
Deepthi Konda, Laxmisha Chandrashekar, Rahul Dhodapkar, Rajesh Nachiappa Ganesh, Devinder Mohan Thappa
Summary: This study characterized the clinical markers of herpes simplex virus (HSV) infection among patients with pemphigus vulgaris. It was found that male sex, presence of fissures, hemorrhagic crusts, erosions with angulated margins, linear erosions, and raised erythrocyte sedimentation rate were significantly associated with HSV infection. Hemorrhagic crusts and linear erosions were identified as independent predictors of HSV infection.
JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY
(2023)
Article
Microbiology
Boqiang Sun, Xuewei Yang, Fujun Hou, Xiaofeng Yu, Qiongyan Wang, Hyung Suk Oh, Priya Raja, Jean M. Pesola, Emilia A. H. Vanni, Seamus McCarron, Jenna Morris-Love, Alex H. M. Ng, George M. Church, David M. Knipe, Donald M. Coen, Dongli Pan
Summary: MicroRNA miR-138 targets ICP0, Oct-1, and Foxc1 to repress HSV-1 lytic cycle genes and promote epigenetic gene silencing, favoring viral latency in neuronal cells. Integration of genome-wide RNA sequencing/PAR-CLIP and short interfering RNA knockdown techniques reveals the mechanism by which miR-138 regulates HSV-1 replication and latency.
NATURE MICROBIOLOGY
(2021)
Article
Immunology
Malgorzata Krzyzowska, Anders Jarneborn, Karolina Thorn, Kristina Eriksson, Tao Jin
Summary: This study provides evidence that treatment with tofacitinib may increase the risk of disease aggravation and severe encephalitis in primary herpes simplex infection by impairing antiviral response induced by monocytes and microglia.
JOURNAL OF INFECTIOUS DISEASES
(2022)
Article
Immunology
Cooper K. Hayes, Christopher K. Villota, Fiona B. McEnany, Stacey Ceron, Sita Awasthi, Moriah L. Szpara, Harvey M. Friedman, David A. Leib, Richard Longnecker, Matthew D. Weitzman, Lisa N. Akhtar
Summary: Clinical HSV-2 isolates collected from neonates with encephalitis are more neurovirulent in human neuronal cell culture and murine models as compared to isolates from neonates with skin-limited disease, suggesting that viral factors contribute to neurologic outcome following human neonatal infection.
JOURNAL OF INFECTIOUS DISEASES
(2022)
Article
Biochemistry & Molecular Biology
Mahmoud Kandeel, Mizuki Yamamoto, Hideki Tani, Ayako Kobayashi, Jin Gohda, Yasushi Kawaguchi, Byoung Kwon Park, Hyung-Joo Kwon, Jun-ichiro Inoue, Abdallah Alkattan
Summary: The study aimed to develop new fusion inhibitors against SARS-CoV-2, designing 12 peptides with peptide #2 demonstrating potent inhibition of SARS-CoV-2 S-mediated cell-cell fusion at 1 μM concentration. This shows promise in the development of new prophylactic and therapeutic agents against SARS-CoV-2.
BIOMOLECULES & THERAPEUTICS
(2021)
Article
Virology
Yuhei Maruzuru, Naoto Koyanagi, Akihisa Kato, Yasushi Kawaguchi
Summary: AIM2 is a cytosolic DNA sensor that plays a critical role in innate immune responses against invading pathogens. VP22, a virion tegument protein of HSV-1, has been found to inhibit AIM2 inflammasome activation by preventing AIM2 oligomerization. This study highlights the importance of VP22's DNA binding activity in inhibiting AIM2 inflammasome activation in HSV-1-infected cells.
JOURNAL OF VIROLOGY
(2021)
Article
Allergy
Akimasa Adachi, Tetsuya Honda, Teruki Dainichi, Gyohei Egawa, Yosuke Yamamoto, Takashi Nomura, Saeko Nakajima, Atsushi Otsuka, Masamitsu Maekawa, Nariyasu Mano, Naoto Koyanagi, Yasushi Kawaguchi, Toshiaki Ohteki, Takashi Nagasawa, Koichi Ikuta, Akihiko Kitoh, Kenji Kabashima
Summary: The study revealed that a single bout of prolonged high-intensity exercise can either impair or enhance the clearance of HSV-2 infection in mice, depending on the timing of exercise post infection. This effect is linked to the temporary decrease or increase in blood-circulating plasmacytoid dendritic cells, regulated by exercise-induced glucocorticoids.
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Yuriko Tachida, Saori Miura, Yui Muto, Hiroyuki Takuwa, Naruhiko Sahara, Akihiro Shindo, Yukio Matsuba, Takashi Saito, Naoyuki Taniguchi, Yasushi Kawaguchi, Hidekazu Tomimoto, Takaomi Saido, Shinobu Kitazume
Summary: The deposition of amyloid P in blood vessels of the brain is commonly observed in Alzheimer's disease patients. However, it is difficult to examine the contribution of cerebral amyloid angiopathy (CAA) to the pathogenesis of Alzheimer's disease in mouse models. Based on biochemical analyses, the researchers hypothesized that endothelial APP expression would be lower in rodents and subsequently generated mice that express human WT APP in endothelial cells. The mice showed increased levels of serum A beta and soluble APP, indicating the crucial role of endothelial APP in blood A beta levels. Crossing these mice with a specific APP knock-in mouse model led to an expanded CAA pathology.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Article
Virology
Fumio Maeda, Akihisa Kato, Kosuke Takeshima, Misato Shibazaki, Ryota Sato, Takuma Shibata, Kensuke Miyake, Hiroko Kozuka-Hata, Masaaki Oyama, Eigo Shimizu, Seiya Imoto, Satoru Miyano, Shungo Adachi, Tohru Natsume, Koh Takeuchi, Yuhei Maruzuru, Naoto Koyanagi, Arii Jun, Kawaguchi Yasushi
Summary: This study developed a screening system to identify cellular proteins involved in the nuclear egress of HSV-1. Through this system, the researchers discovered that the cellular orphan transporter SLC35E1 plays a critical role in HSV-1 de-envelopment.
JOURNAL OF VIROLOGY
(2022)
Article
Microbiology
Mizuki Yamamoto, Jin Gohda, Ayako Kobayashi, Keiko Tomita, Youko Hirayama, Naohiko Koshikawa, Motoharu Seiki, Kentaro Semba, Tetsu Akiyama, Yasushi Kawaguchi, Jun-ichiro Inoue
Summary: The study found that the cell surface entry pathway of SARS-CoV-2 includes a metalloproteinase-mediated pathway in addition to the TMPRSS2 and endosomal pathways. The metalloproteinase-mediated pathway requires prior cleavage of the spike protein into two domains, a condition met by SARS-CoV-2 but not by the related human coronavirus SARS-CoV. Additionally, inhibiting metalloproteins was crucial in preventing cell death, which may lead to organ damage. The findings provide new insights into the unique pathogenesis of COVID-19 and are relevant to the development of effective therapies.
Article
Virology
Kosuke Takeshima, Yuhei Maruzuru, Naoto Koyanagi, Akihisa Kato, Yasushi Kawaguchi
Summary: This study demonstrates the redundant functions of lamin A/C and LBR in regulating HSV-1 gene expression and DNA replication through the dynamics of nuclear architecture. It also reveals the involvement of LBR in the regulation of viral and cellular features during HSV-1 infection.
JOURNAL OF VIROLOGY
(2022)
Article
Immunology
Ayano Fukui, Yuhei Maruzuru, Kosuke Takeshima, Naoto Koyanagi, Akihisa Kato, Yasushi Kawaguchi
Summary: In this study, a system was established to measure the frequency of cell-cell fusion induced by wild-type herpes simplex virus (HSV) strains. It was found that the HSV-1 envelope glycoprotein B and its N-glycosylation at asparagine at position 141 were necessary for efficient cell-cell fusion. This study provides insight into the connection between wild-type HSV-1-induced cell-cell fusion and viral pathogenesis in vivo.
MICROBIOLOGY AND IMMUNOLOGY
(2023)
Article
Multidisciplinary Sciences
Hideki Ogura, Jin Gohda, Xiuyuan Lu, Mizuki Yamamoto, Yoshio Takesue, Aoi Son, Sadayuki Doi, Kazuyuki Matsushita, Fumitaka Isobe, Yoshihiro Fukuda, Tai-Ping Huang, Takamasa Ueno, Naomi Mambo, Hiromoto Murakami, Yasushi Kawaguchi, Jun-ichiro Inoue, Kunihiro Shirai, Sho Yamasaki, Jun-Ichi Hirata, Satoshi Ishido
Summary: This study explores the characteristics of virus-specific CTLs related to the severity of COVID-19. Through the establishment of a cellular screening method, the researchers found that the SARS-CoV-2 M protein is a frequent target of CD8(+) T cells, and identified M198-206 as an immunoprevalent epitope in convalescent COVID-19 patients. Further single cell RNA sequencing revealed an exhausted phenotype with less differentiated status in cells from the severe group compared to cells from the moderate group.
NATURE COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Kazuto Takahashi, Kenji Kanekiyo, Kanoko Sakuda, Yui Muto, Masahiro Iguchi, Nozomu Matsuda, Yuko Hashimoto, Kazuaki Kanai, Haruko Ogawa, Hajime Hirase, Akiyoshi Kakita, Norihisa Bizen, Hirohide Takebayashi, Yasushi Kawaguchi, Miwa Uzuki, Shinobu Kitazume
Summary: Astrocytes, specifically those expressing HNK-1-O-Man(+) PTPRZ, play a crucial role in demyelination-associated conditions such as multiple sclerosis. This unique glycosylation pattern of PTPRZ is responsible for the pattern of reactive astrocytes in damaged brain areas. Understanding the role of HNK-1-O-Man(+) PTPRZ in astrocytes can provide insights into the development and progression of brain diseases.
JOURNAL OF NEUROCHEMISTRY
(2023)
Article
Cell Biology
Yoshihiko Kuchitsu, Kojiro Mukai, Rei Uematsu, Yuki Takaada, Ayumi Shinojima, Ruri Shindo, Tsumugi Shoji, Shiori Hamano, Emari Ogawa, Ryota Sato, Kensuke Miyake, Akihisa Kato, Yasushi Kawaguchi, Masahiko Nishitani-Isa, Kazushi Izawa, Ryuta Nishikomori, Takahiro Yasumi, Takehiro Suzuki, Naoshi Dohmae, Takefumi Uemura, Glen N. N. Barber, Hiroyuki Arai, Satoshi Waguri, Tomohiko Taguchi
Summary: Stimulator of interferon genes (STING) is crucial for the immune response against DNA pathogens, and its degradation is mediated by endosomal sorting complexes required for transport (ESCRT) proteins. STING-positive vesicles derived from recycling endosomes are encapsulated into lysosomes after STING ubiquitination. This study provides insights into the regulation of STING and prevents hyperactivation of the immune response.
NATURE CELL BIOLOGY
(2023)
Article
Virology
Ahmed H. E. Hassan, Selwan M. M. El-Sayed, Mizuki Yamamoto, Jin Gohda, Takehisa Matsumoto, Mikako Shirouzu, Jun-ichiro Inoue, Yasushi Kawaguchi, Reem M. A. Mansour, Abtin Anvari, Abdelbasset A. A. Farahat
Summary: Coronaviruses and other viruses rely on host proteases for cell entry. Targeting the conserved host-based entry mechanism instead of viral proteins may be advantageous. Compound 14 is identified as a potential starting point for developing viral entry inhibitors.
Article
Immunology
Joseph K. Sampson Duncan, Danyang Xu, Maria Licursi, Michael A. Joyce, Holly A. Saffran, Kaiwen Liu, Jin Gohda, D. Lorne Tyrrell, Yasushi Kawaguchi, Kensuke Hirasawa
Summary: Interferon regulatory factors (IRFs) play important roles in regulating the antiviral response against human coronaviruses. Activation of IRF1, IRF3, and IRF7 is observed during infection with different strains of coronaviruses. Knockdown and overexpression experiments demonstrate that IRF1 and IRF3 have antiviral properties against OC43, while IRF3 and IRF7 are effective in restricting 229E infection. Our study highlights the potential of IRFs as antiviral regulators against human coronavirus infection.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Microbiology
Yujin Inayoshi, Shiori Oguro, Erika Tanahashi, Zhifeng Lin, Yasushi Kawaguchi, Toshiaki Kodama, Chihiro Sasakawa
Summary: A reverse genetics system was established in this study to clone and manipulate the avian infectious bronchitis virus (IBV) genome, providing a useful platform for analyzing the pathogenesis of IBV and developing new vaccines.
CURRENT RESEARCH IN MICROBIAL SCIENCES
(2022)
Article
Virology
Jun Arii, Kosuke Takeshima, Yuhei Maruzuru, Naoto Koyanagi, Yoshitaka Nakayama, Akihisa Kato, Yasuko Mori, Yasushi Kawaguchi
Summary: This study identifies an arginine cluster in the disordered domain of UL34 that interacts with ALIX and recruits ESCRT-III machinery for primary envelopment. The study highlights the importance of the disordered domain of UL34 in herpesvirus infections.
JOURNAL OF VIROLOGY
(2022)