Article
Microbiology
Ming Li, Qiaolin Hu, Geoffrey Collins, Mrutyunjaya Parida, Christopher B. Ball, David H. Price, Jeffery L. Meier
Summary: The HCMV UL79 and UL87 LTFs function together to initiate transcription from over half of active viral promoters in late infection without significantly affecting host transcription. Some viral core promoters lack the TATT motif and instead have alternative sequences. Diversity in LTF target sequences shapes the transformative program that drives the viral transcription switch.
Article
Fisheries
Thaneeya Nantapojd, Sakol Panyim, Chalermporn Ongvarrasopone
Summary: The study found that wsv-miR-9 plays an important role in early viral gene expression, leading to a delay in viral replication when its expression is inhibited. This highlights the potential for wsv-miR-9 as a target for controlling WSSV infection in shrimp.
Article
Biotechnology & Applied Microbiology
Stefanie Herb, Jelena Zeleznjak, Thomas Hennig, Anne L'Hernault, Manivel Lodha, Christopher Jurges, Tihana Trsan, Vanda Juranic Lisnic, Stipan Jonjic, Florian Erhard, Astrid Krmpotic, Lars Dolken
Summary: Human cytomegalovirus is a major cause of morbidity and mortality in immune compromised patients. The virus-encoded microRNAs (miRNAs) could be potential targets for new antiviral agents. By investigating the targets of mouse cytomegalovirus (MCMV) miRNAs, we discovered that specific miRNAs have a significant impact on viral plaque formation and replication.
JOURNAL OF GENERAL VIROLOGY
(2022)
Article
Microbiology
Ana Cristina Gonzalez-Perez, Markus Stempel, Emanuel Wyler, Christian Urban, Antonio Piras, Thomas Hennig, Sabina Ganskih, Yuanjie Wei, Albert Heim, Markus Landthaler, Andreas Pichlmair, Lars Doelken, Mathias Munschauer, Florian Erhard, Melanie M. Brinkmann
Summary: The study revealed the role of ZAP during HCMV infection, slowing down the viral gene expression cascade by degrading specific viral transcripts and negatively affecting HCMV replication. It provides a new avenue for exploring potential targets for novel therapies.
Review
Genetics & Heredity
Shaylee R. Kieffer, Noel F. Lowndes
Summary: Loss or rearrangement of genetic information can occur due to incorrect responses to DNA double strand breaks (DSBs). Cellular responses to DSBs involve coordinated events to detect and appropriately respond to the damage, preserving genomic integrity. This article discusses the complex regulation of the immediate-early, early, and late responses to DSBs prior to repair.
FRONTIERS IN GENETICS
(2022)
Article
Microbiology
Salome Manska, Cyprian C. Rossetto
Summary: Human cytomegalovirus (HCMV) IE2 protein is essential for viral gene expression and is modulated by UL84 protein to relieve transcriptional repression. Some strains of HCMV can replicate independently of UL84 due to a single amino acid change in IE2.
MICROBIOLOGY SPECTRUM
(2021)
Correction
Cell Biology
Le Wen, Fei Zhao, Yong Qiu, Shuang Cheng, Jin-Yan Sun, Wei Fang, Simon Rayner, Michael A. McVoy, Xing-Jun Jiang, Qiyi Tang, Fang-Cheng Li, Fei Hu, Min-Hua Luo
Summary: This correction provides the correct email addresses of corresponding authors that were not displayed in the original publication.
Article
Multidisciplinary Sciences
E. A. Monson, K. M. Crosse, M. Duan, W. Chen, R. D. O'Shea, L. M. Wakim, J. M. Carr, D. R. Whelan, K. J. Helbig
Summary: Lipid droplets (LDs) are critical in enhancing modulation of IFN, controlling viral replication, and facilitating early antiviral immune response, marking a paradigm shift in understanding the molecular mechanisms of effective antiviral responses.
NATURE COMMUNICATIONS
(2021)
Article
Cell Biology
Enrico Caragliano, Stefano Bonazza, Giada Frascaroli, Jiajia Tang, Timothy K. Soh, Kay Grunewald, Jens B. Bosse, Wolfram Brune
Summary: Human cytomegalovirus forms replication compartments in the host cell nucleus using liquid-liquid phase separation with specific proteins, ensuring efficient viral genome replication.
Article
Microbiology
Jian Xu, Yunhong Cai, ZhenBang Ma, Bo Jiang, Wenxiao Liu, Jing Cheng, Nannan Guo, Zishu Wang, Joshua E. Sealy, Cuiping Song, Xiaojia Wang, Yongqing Li
Summary: The study reveals that DDX5 negatively regulates innate immunity by manipulating RNA m6A modification. DDX5 recruits RNA m6A writer METTL3 to control the m6A writer complex, specifically promotes m6A modification and nuclear export of DDX5 binding transcripts in innate immune response, ultimately leading to RNA decay of antiviral transcripts in a YTHDF2-dependent manner.
Article
Multidisciplinary Sciences
Gloria Griffante, Francesca Gugliesi, Selina Pasquero, Valentina Dell'Oste, Matteo Biolatti, Ari J. Salinger, Santanu Mondal, Paul R. Thompson, Eranthie Weerapana, Robert J. Lebbink, Jasper A. Soppe, Thomas Stamminger, Virginie Girault, Andreas Pichlmair, Gabor Oroszlan, Donald M. Coen, Marco De Andrea, Santo Landolfo
Summary: Citrullination as a posttranslational modification plays a crucial role in HCMV infection, promoting viral entry and impairing the RNA binding ability of citrullinated IFIT1 as a mechanism of evasion.
NATURE COMMUNICATIONS
(2021)
Article
Microbiology
Tejaswini S. Reddi, Philipp E. Merkl, So-Yon Lim, Norman L. Letvin, David M. Knipe
Summary: TRIM22 is a novel restriction factor that can combat DNA viruses, particularly HSV-1, and is not degraded by viral ICP0 protein. It also inhibits other types of herpesviruses and different genetic variants of TRIM22 show varying levels of effectiveness against HSV-1.
Article
Virology
Xue-Hui Ma, Yong-Xuan Yao, Xian-Zhang Wang, Yue-Peng Zhou, Sheng-Nan Huang, Dong Li, Meng-Jie Mei, Jing-Peng Wu, Yu-Ting Pan, Shuang Cheng, Xuan Jiang, Jin-Yan Sun, Wen-Bo Zeng, Sitang Gong, Han Cheng, Min-Hua Luo, Bo Yang
Summary: During the coevolution of human cytomegalovirus (HCMV) and humans, the host has developed a defense system while the virus has devised strategies to evade detection. MORC3, a component of PML-NBs, is identified as a restriction factor targeting HCMV infection. HCMV induces temporary reduction of MORC3 protein level to evade its repression against immediate-early gene expression.
JOURNAL OF MEDICAL VIROLOGY
(2022)
Article
Microbiology
D. Hoffman, W. Rodriguez, D. Macveigh-Fierro, J. Miles, M. Muller
Summary: This study explores the role of the poorly characterized viral protein ORF20 in KSHV replication, showing its interaction with ORF59 in replication compartments and its impact on DNA replication and late viral lifecycle stages. These findings suggest ORF20's potential contribution as a key modulator of the complex lytic DNA replication process within KSHV.
MICROBIOLOGY SPECTRUM
(2021)
Article
Multidisciplinary Sciences
Ke Xiao, Dan Xiong, Gong Chen, Jinsong Yu, Yue Li, Kening Chen, Lu Zhang, Yangyang Xu, Qian Xu, Xi Huang, Anran Gao, Kai Cao, Keji Yan, Jinxia Dai, Xueying Hu, Yijun Ruan, Zhenfang Fu, Guoliang Li, Gang Cao
Summary: This study demonstrates a genome-wide trans-species chromatin interaction between pseudorabies virus (PRV) and host cells, where the viral genome is delivered into the open and active chromatin zone by the host DNA binding protein RUNX1. This facilitates viral gene transcription by hijacking host transcription machinery, a process significantly inhibited by either a RUNX1 inhibitor or RNA interference. These findings provide insights into herpesvirus genome transcription and suggest new research directions in this area.
Review
Virology
Yousef M. O. Alhammad, Anthony R. Fehr
Article
Biochemistry & Molecular Biology
Collin D. Heer, Daniel J. Sanderson, Lynden S. Voth, Yousef M. O. Alhammad, Mark S. Schmidt, Samuel A. J. Trammell, Stanley Perlman, Michael S. Cohen, Anthony R. Fehr, Charles Brenner
JOURNAL OF BIOLOGICAL CHEMISTRY
(2020)
Article
Virology
Lynden S. Voth, Joseph J. O'Connor, Catherine M. Kerr, Ethan Doerger, Nancy Schwarting, Parker Sperstad, David K. Johnson, Anthony R. Fehr
Summary: The macrodomain Mac1 within nonstructural protein 3 of coronaviruses has been identified as essential for viral replication, with targeted mutations revealing multiple functions that contribute to the replication of the model CoV MHV. These findings suggest that Mac1 may be a potential target for anti-CoV therapeutics.
JOURNAL OF VIROLOGY
(2021)
Article
Biochemistry & Molecular Biology
Bernhard Luscher, Ivan Ahel, Matthias Altmeyer, Alan Ashworth, Peter Bai, Paul Chang, Michael Cohen, Daniela Corda, Francoise Dantzer, Matthew D. Daugherty, Ted M. Dawson, Valina L. Dawson, Sebastian Deindl, Anthony R. Fehr, Karla L. H. Feijs, Dmitri V. Filippov, Jean-Philippe Gagne, Giovanna Grimaldi, Sebastian Guettler, Nicolas C. Hoch, Michael O. Hottiger, Patricia Korn, W. Lee Kraus, Andreas Ladurner, Lari Lehtio, Anthony K. L. Leung, Christopher J. Lord, Aswin Mangerich, Ivan Matic, Jason Matthews, George-Lucian Moldovan, Joel Moss, Gioacchino Natoli, Michael L. Nielsen, Mario Niepel, Friedrich Nolte, John Pascal, Bryce M. Paschal, Krzysztof Pawlowski, Guy G. Poirier, Susan Smith, Gyula Timinszky, Zhao-Qi Wang, Jose Yelamos, Xiaochun Yu, Roko Zaja, Mathias Ziegler
Summary: ADP-ribosylation, a post-translational modification of proteins, nucleic acids, and metabolites, plays diverse roles in cellular processes such as stress responses, signaling, and transcriptional regulation. Recent advances in research have identified a wide range of cellular pathways regulated by ADP-ribosylation, highlighting the importance of understanding this mechanism in cell biology.
Article
Biochemistry & Molecular Biology
Morgan Dasovich, Junlin Zhuo, Jack A. Goodman, Ajit Thomas, Robert Lyle McPherson, Aravinth Kumar Jayabalan, Veronica F. Busa, Shang-Jung Cheng, Brennan A. Murphy, Karli R. Redinger, Yousef M. O. Alhammad, Anthony R. Fehr, Takashi Tsukamoto, Barbara S. Slusher, Jurgen Bosch, Huijun Wei, Anthony K. L. Leung
Summary: Viral macrodomains are crucial for virus replication and pathogenesis, making them a promising target for antiviral therapy. Dasatinib has been identified as a potential ADP-ribosylhydrolase inhibitor, showing effectiveness against SARS-CoV-2 and MERS-CoV, but not affecting the closest human homologue MacroD2. This study demonstrates the feasibility of identifying selective inhibitors based on ADP-ribosylhydrolase activity and provides a potential avenue for developing better macrodomain inhibitors as antiviral therapies for SARS-CoV-2 and other viral threats.
ACS CHEMICAL BIOLOGY
(2022)
Article
Microbiology
Anthony K. L. Leung, Diane E. Griffin, Juergen Bosch, Anthony R. Fehr
Summary: Emerging and re-emerging viral diseases pose continuous threats to public health. Developing a diverse portfolio of antiviral agents is crucial for effective control. The macrodomain, a drug target critical for the replication and pathogenesis of alphaviruses and coronaviruses, has the potential to block virus replication and restore the host's protective interferon response. Macrodomain inhibitors, with their well-defined binding pocket, offer an attractive target for developing direct acting antivirals and complementing current approaches in combating COVID-19 and future viral threats.
Article
Multidisciplinary Sciences
Courtney E. Comar, Clayton J. Otter, Jessica Pfannenstiel, Ethan Doerger, David M. Renner, Li Hui Tan, Stanley Perlman, Noam A. Cohen, Anthony R. Fehr, Susan R. Weiss
Summary: MERS-CoV optimizes its replication by suppressing early innate immune pathways, including interferon production and signaling, through the actions of endoribonuclease (EndoU) and accessory proteins NS4a and NS4b.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Pharmacology & Pharmacy
Anu Roy, Yousef M. Alhammad, Peter McDonald, David K. Johnson, Junlin Zhuo, Sarah Wazir, Dana Ferraris, Lari Lehtio, Anthony K. L. Leung, Anthony R. Fehr
Summary: This study focuses on screening for potential inhibitors of the SARS-CoV-2 conserved macrodomain (Mac1). Five compounds from three chemotypes were identified, which show inhibitory effects on Mac1-ADP-ribose binding, ADP-ribosylhydrolase activity, and direct Mac1 binding, making them strong candidates for the development of highly effective Mac1 inhibitors.
ANTIVIRAL RESEARCH
(2022)
Article
Biochemistry & Molecular Biology
Lavinia M. Sherrill, Elva E. Joya, AnnMarie Walker, Anuradha Roy, Yousef M. Alhammad, Moriama Atobatele, Sarah Wazir, George Abbas, Patrick Keane, Junlin Zhuo, Anthony K. L. Leung, David K. Johnson, Lari Lehtio, Anthony R. Fehr, Dana Ferraris
Summary: A series of amino acid based compounds were designed and synthesized to investigate their inhibitory activity against the SARS-CoV-2 nsp3 macrodomain. Compound 15c was identified as a low-micromolar inhibitor and demonstrated selectivity for coronavirus macrodomains.
BIOORGANIC & MEDICINAL CHEMISTRY
(2022)
Article
Microbiology
Srivatsan Parthasarathy, Anthony R. Fehr
Summary: The translation discusses the impact of posttranslational modifications (PTMs) on protein functions, focusing on the role of ADP-ribosylation. Specifically, it highlights the importance of PARP14, a MARylating enzyme, in anti-inflammatory and antiviral responses, while also emphasizing the need for further studies to elucidate its specific roles and mechanisms during viral infections.
Article
Microbiology
Cindy Y. Ly, Jessica Pfannenstiel, Anil Pant, Zhilong Yang, Anthony R. Fehr, Maxim S. Rodzkin, David J. Davido
Summary: In this study, aurora kinase inhibitors were found to significantly reduce gene expression and viral replication of herpes simplex virus 1 (HSV-1). Furthermore, these inhibitors also showed inhibitory effects on the replication of other RNA and DNA viruses. These findings suggest a novel role for aurora kinases in the replication of diverse viruses.
MICROBIOLOGY SPECTRUM
(2023)
Article
Virology
Catherine M. Kerr, Srivatsan Parthasarathy, Nancy Schwarting, Joseph J. O'Connor, Jessica J. Pfannenstiel, Emily Giri, Sunil More, Robin C. Orozco, Anthony R. Fehr
Summary: PARP12 is an important mediator of the antiviral response to coronaviruses, but additional PARPs or innate immune factors contribute to virus attenuation in mice. PARP12 knockout increases Mac1 mutant virus replication and liver pathology in mice.
JOURNAL OF VIROLOGY
(2023)
Article
Microbiology
Joseph J. O'Connor, Lynden Voth, Jeremiah Athmer, Nicholas M. George, Christopher M. Connelly, Anthony R. Fehr
Summary: Testing two commercially available blood collection tube blood-stabilization reagents, cfDNA and CytoChex, it was found that they can rapidly inactivate coronaviruses and effectively preserve viral RNA stability for a certain period of time.
Review
Microbiology
Joseph J. O'Connor, Dana Ferraris, Anthony R. Fehr
Summary: This article summarizes the progress in the search for inhibitors of the SARS-CoV-2 Mac1 protein. Various unique chemical inhibitors have been successfully created using high-throughput screening and chemical modifications.
Article
Virology
Yousef M. O. Alhammad, Maithri M. Kashipathy, Anuradha Roy, Jean-Philippe Gagne, Peter McDonald, Philip Gao, Louis Nonfoux, Kevin P. Battaile, David K. Johnson, Erik D. Holmstrom, Guy G. Poirier, Scott Lovell, Anthony R. Fehr
Summary: The Mac1 proteins in SARS-CoV-2 and other CoVs are MAR-hydrolases with similar functions, suggesting compounds targeting these proteins may have broad anti-CoV activity. Understanding the biochemistry and enzyme activity of these proteins is critical for developing novel therapeutic strategies against COVID-19.
JOURNAL OF VIROLOGY
(2021)