Article
Microbiology
Xian-Zhang Wang, Le Wen, Yue-Peng Zhou, Sheng-Nan Huang, Bo Yang, Shuang Cheng, Wen-Bo Zeng, Meng-Jie Mei, Jin-Yan Sun, Xuan Jiang, Han Cheng, Min-Hua Luo
Summary: Congenital human cytomegalovirus (HCMV) infection leads to severe damage to the fetal brain. In this study, we discovered a new regulatory mechanism by which sustained SOCS3 expression is upregulated in HCMV-infected neural progenitor cells (NPCs). We found that the viral protein pUL97 interacts with and phosphorylates the host transcription factor RFX7, which drives the transcription of SOCS3. Elevated SOCS3 expression impairs NPC cell proliferation and migration, thereby affecting fetal brain development.
Article
Microbiology
Han Chen, Ming F. Lye, Christoph Gorgulla, Scott B. Ficarro, Gregory D. Cuny, David A. Scott, Fan Wu, Paul W. Rothlauf, Xiaoou Wang, Rosio Fernandez, Jean M. Pesola, Sorin Draga, Jarrod A. Marto, James M. Hogle, Haribabu Arthanari, Donald M. Coen
Summary: The study found that two small molecule compounds, GK1 and GK2, selectively inhibit the replication of human cytomegalovirus (HCMV) by targeting the nuclear egress complex (NEC). These compounds could serve as a foundation for the development of anti-HCMV drugs and as chemical tools for studying HCMV.
Article
Pharmacology & Pharmacy
Samuel D. Chorlton, Gordon Ritchie, Tanya Lawson, Elizabeth McLachlan, Marc G. Romney, Nancy Matic, Christopher F. Lowe
Summary: A next-generation sequencing (NGS) assay was developed for CMV antiviral drug resistance (AVDR) testing, which using MinION technology detected additional mutations compared to traditional Sanger sequencing. Through the application of an online bioinformatics pipeline, barriers associated with MinION and NGS in clinical laboratories were eliminated.
ANTIVIRAL RESEARCH
(2021)
Article
Cell Biology
Natalia Landazuri, Jennifer Gorwood, Ylva Terelius, Fredrik oberg, Koon Chu Yaiw, Afsar Rahbar, Cecilia Soderberg-Naucler
Summary: HCMV infection is a significant cause of morbidity and mortality, with ganciclovir being the preferred treatment. Testing the hypothesis that ETBR blockade could be used in the treatment of HCMV infection, the study found that ETBR blockers effectively inhibited productive infection of HCMV, including a ganciclovir-resistant isolate. This suggests that binding or signaling through ETBR is crucial for viral replication and selected blockers can inhibit HCMV infection.
Article
Immunology
Caroline L. Ashley, Brian P. McSharry, Hamish E. G. McWilliam, Richard J. Stanton, Ceri A. Fielding, Rommel A. Mathias, David P. Fairlie, James McCluskey, Jose A. Villadangos, Jamie Rossjohn, Allison Abendroth, Barry Slobedman
Summary: This study reveals that human cytomegalovirus (HCMV) inhibits the MR1 pathway and disrupts the MR1:MAIT cell axis through the viral protein gpUS9. The interaction between this virus and MAIT cells in the context of viral infection is not well characterized.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Pharmacology & Pharmacy
Sunwen Chou, Matthew Watters, Rohita Sinha, Steven Kleiboeker
Summary: Research has found that mutations in the UL97 gene of cytomegalovirus, specifically in the ATP binding region, may impact the resistance to ganciclovir and maribavir. Therefore, it is suggested to include testing of the UL97 ATP binding region in the standard diagnostic genotyping for better interpretation of drug resistance.
ANTIVIRAL RESEARCH
(2021)
Article
Multidisciplinary Sciences
Ana Catarina Menezes, Christabel Dixon, Anna Scholz, Rachael Nicholson, Adam Leckenby, Aleksandra Azevedo, Sarah Baker, Amanda F. Gilkes, Sara Davies, Richard L. Darley, Alex Tonks
Summary: This study demonstrates the regulatory role of RUNX3 in normal human erythropoiesis. RUNX3 has a modest impact on early erythroid growth and development, but promotes growth and inhibits terminal differentiation in late-stage erythroid development. Overexpression of RUNX3 increases colony formation in liquid culture.
SCIENTIFIC REPORTS
(2022)
Article
Virology
Seungwan Chae, Hoon Seok Kim, Sung-Yeon Cho, Dukhee Nho, Raeseok Lee, Dong-Gun Lee, Myungshin Kim, Yonggoo Kim
Summary: This study aimed to identify variants associated with CMV drug resistance in HCT recipients and assess their clinical significance. The study found that 8.1% of patients had resistance variants, and 39.0% of patients had variants of uncertain significance. Patients with resistance variants had higher CMV viral load and higher risks of severe graft-versus-host disease and lower one-year survival rates.
Article
Oncology
Ana Catarina Menezes, Rachel Jones, Alina Shrestha, Rachael Nicholson, Adam Leckenby, Aleksandra Azevedo, Sara Davies, Sarah Baker, Amanda F. Gilkes, Richard L. Darley, Alex Tonks
Summary: The role of RUNX3 in normal myeloid development and leukemia, particularly acute myeloid leukemia (AML), is investigated. The study shows that increased expression of RUNX3 in AML can contribute to the developmental arrest characteristic of the disease. Overexpression of RUNX3 inhibits myeloid differentiation and proliferation in human hematopoietic stem and progenitor cells (HSPC), while RUNX3 knockdown does not impact myeloid growth and development. These findings suggest that dysregulation of RUNX3 may play an important role in the pathogenesis of AML.
Article
Immunology
Jingui Deng, Qing Wang, Jing Zhang, Yanping Ma, Ying Qi, Zhongyang Liu, Yibo Li, Qiang Ruan, Yujing Huang
Summary: HCMV-encoded circRNAs are abundantly expressed during HCMV infection. A total of 629 HCMV-encoded circRNAs were identified using RNA deep sequencing. The study verified the existence and transcription of circUS12, circUL55, and circUL89, and revealed the potential roles of HCMV-encoded circRNAs in HCMV infection.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2022)
Article
Cell Biology
Ana Rita Ferreira, Ana Gouveia, Ana Cristina Magalhaes, Isabel Valenca, Mariana Marques, Jonathan C. Kagan, Daniela Ribeiro
Summary: The human cytomegalovirus has developed a protein called vMIA to evade the antiviral response of cells. This protein inhibits the signaling pathway that fights viral infections by interacting with the mitochondria and peroxisomes. This study uncovers the specific mechanisms by which vMIA interacts with these organelles and highlights the importance of peroxisomes in the antiviral response against the human cytomegalovirus.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Virology
Sina Brenner, Berenike Braun, Clarissa Read, Tatjana Weil, Paul Walther, Thomas Schrader, Jan Muench, Jens von Einem
Summary: CLR01 is a broad-spectrum antiviral agent that inhibits both cell-free virus infection and cell-to-cell spread of HCMV, as well as herpes simplex viruses 1 and 2. The rapid inactivation of viral particles by CLR01, its ability to target the viral envelope, and inhibition of virus entry at different stages make it a promising antiviral agent for treating severe HCMV infections and preventing virus dissemination within the host.
Article
Multidisciplinary Sciences
Yujie Ren, An Wang, Bowen Zhang, Wenting Ji, Xiao-Xu Zhu, Jing Lou, Muhan Huang, Yang Qiu, Xi Zhou
Summary: UL36 encoded by human cytomegalovirus not only inhibits apoptosis but also suppresses immune signaling by targeting IRF3 directly. Although UL36-mediated inhibition of apoptosis enhances immune signaling, its immunosuppressive activity counterbalances this effect.
Article
Cell Biology
Mayu Sun, Xueqi Ma, Wei Mu, Haonan Li, Xiaoming Zhao, Tengfei Zhu, Jingquan Li, Yongliang Yang, Haibing Zhang, Qian Ba, Hui Wang
Summary: This study identified Vemurafenib, an FDA-approved anti-cancer drug, as a potent inhibitor of necroptosis. By directly binding to receptor-interacting protein kinases 1 (RIPK1), Vemurafenib blocked their kinase activity and inhibited necroptosis. Furthermore, pre-treatment with Vemurafenib showed strong protection against necroptosis-associated diseases in vivo.
CELL DEATH & DISEASE
(2023)
Article
Infectious Diseases
Uet Yu, Xiaodong Wang, Xiaoling Zhang, Chunjing Wang, Chunlan Yang, Xiaohui Zhou, Yue Li, Xiaochan Huang, Jing Wen, Feiqiu Wen, Sixi Liu
Summary: Drug-resistant cytomegalovirus (CMV) infection remains a challenge in pediatric recipients of hematopoietic stem cell transplantation (HSCT). Mutations in the UL97 and UL54 genes may be associated with the development of drug-resistant CMV infection, providing guidance for the management of post-transplant CMV infections.
INFECTIOUS DISEASES AND THERAPY
(2021)
