Article
Virology
Benjamin E. Nilsson-Payant, Benjamin R. TenOever, Aartjan J. W. te Velthuis
Summary: ANP32A is essential for both vRNA and cRNA synthesis in influenza A virus replication. This new understanding provides insights into the replication and host adaptation of influenza A viruses.
JOURNAL OF VIROLOGY
(2022)
Article
Immunology
Gang Lu, Feiyan Zheng, Jiajun Ou, Xin Yin, Shoujun Li
Summary: In this study, the feline RNA PolI promoter was identified and found to have higher transcriptional activity in feline cells. The equine influenza virus showed higher polymerase activity compared to human and canine influenza viruses. Additionally, the feline myxovirus resistance protein 1 and baloxavir were found to inhibit influenza virus polymerase activity.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Sheng Lin, Hua Chen, Zimin Chen, Fanli Yang, Fei Ye, Yue Zheng, Jing Yang, Xi Lin, Honglu Sun, Lingling Wang, Ao Wen, Haohao Dong, Qingjie Xiao, Dong Deng, Yu Cao, Guangwen Lu
Summary: The emergence of SARS-CoV-2 infection poses an unprecedented threat to global public health, with the virus-encoded nsp14 protein playing a critical role in viral replication. Research demonstrates that the SARS-CoV-2 nsp10/nsp14-ExoN complex, along with the binding of the nsp10 co-factor, maintains both structural and functional integrity.
NUCLEIC ACIDS RESEARCH
(2021)
Article
Pharmacology & Pharmacy
Lirun Zhou, Lei Bao, Yaxin Wang, Mengping Chen, Yingying Zhang, Zihan Geng, Ronghua Zhao, Jing Sun, Yanyan Bao, Yujing Shi, Rongmei Yao, Shanshan Guo, Xiaolan Cui
Summary: Geniposide, extracted from Gardenia jasminoides J.Ellis, has been found to possess pleiotropic activity against various diseases, particularly showing good therapeutic effects on different strains of influenza virus. The study explored the mechanism of geniposide on influenza A virus (IAV) through network pharmacology analysis, revealing a multi-target inhibitory effect on influenza, with one of the mechanisms being the calcium signaling pathway. Experimental data demonstrated that geniposide alleviates extracellular Ca2+ influx, decreases neuraminidase activity, and suppresses IAV replication in vitro by disrupting the interplay between IAV RNA polymerase and CAMKII.
FRONTIERS IN PHARMACOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Zihan Zhu, Ervin Fodor, Jeremy R. Keown
Summary: Influenza virus replication relies on the RNA-dependent RNA polymerase and viral ribonucleoprotein complex. Recent structural data have provided insights into the molecular mechanisms of influenza virus genome replication, particularly in terms of the encapsidation of nascent RNA, de novo assembly of ribonucleoprotein complexes, and the regulation of replication initiation through interactions with host and viral cues.
TRENDS IN MICROBIOLOGY
(2023)
Article
Biology
Jennifer E. Jones, Valerie Le Sage, Gabriella H. Padovani, Michael Calderon, Erik S. Wright, Seema S. Lakdawala
Summary: Influenza viruses evolve rapidly during infection through mutations or reassortment, potentially leading to strains with increased resistance or infectivity. Understanding how genome segments interact during reassortment can help predict future events and emergence of new pandemic strains. Research in this area could provide valuable insights for risk assessment and pandemic preparedness.
Article
Multidisciplinary Sciences
Adrien Chauvier, Patrick St-Pierre, Jean-Francois Nadon, Elsa D. M. Hien, Cibran Perez-Gonzalez, Sebastien H. Eschbach, Anne-Marie Lamontagne, J. Carlos Penedo, Daniel A. Lafontaine
Summary: The researchers presented a new approach for site-specific labeling and smFRET studies of kilobase-length transcripts within native bacterial complexes, revealing the relationship between RNA folding and gene regulation.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Multidisciplinary Sciences
Xizi Chen, Xinxin Wang, Weida Liu, Yulei Ren, Xuechun Qu, Jiabei Li, Xiaotong Yin, Yanhui Xu
Summary: RNA polymerase II-mediated eukaryotic transcription begins with the assembly of the preinitiation complex (PIC) on core promoters. The +1 nucleosome, positioned about 40 base pairs downstream of the transcription start site (TSS), acts as a barrier to transcription. The study shows that the PIC-Mediator prefers binding to the T40N nucleosome located at the 40 base pairs downstream of the TSS and contacts the T50N nucleosome, but not the T70N nucleosome. The nucleosome facilitates the organization of PIC-Mediator on the promoter and may contribute to transcription initiation. The study reveals the molecular mechanism of PIC-Mediator organization on chromatin and emphasizes the significance of the +1 nucleosome in regulating transcription initiation.
Article
Biochemistry & Molecular Biology
Shinzi Ogasawara, Sae Ebashi
Summary: Researchers have developed an RNA editing technology called RNA overwriting, which utilizes the RNA-dependent RNA polymerase (RdRp) of the influenza A virus to overwrite the sequence downstream of a designated site on target RNA. By introducing mutations and fusing with catalytically inactive Cas13b, the modified RdRp can knock down target mRNA and perform sequence overwriting within living cells. This versatile editing technique allows for the repair of aberrant mRNA caused by dysregulation of mRNA processing.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Cell Biology
Long Vo Ngoc, Torrey E. Rhyne, James T. Kadonaga
Summary: In this study, machine learning was used to compare DPR region, a DNA motif involved in transcription initiation, in humans and Drosophila. A distinct human-specific version of DPR was identified and machine learning models were used to predict synthetic DPR motifs with specificity for human transcription factors. These findings demonstrate the potential of machine learning in designing synthetic DNA elements with specific functional properties.
GENES & DEVELOPMENT
(2023)
Article
Biochemistry & Molecular Biology
Xiaoxian Wu, Chengzhi Yu, Wenhui Mu, Zhanxi Gu, Yu Feng, Yu Zhang
Summary: Canonical bacterial transcription activators bind to their cognate cis elements at the upstream of transcription start site (TSS) in a form of dimer. Caulobacter crescentus GcrA, a non-canonical transcription activator, can activate transcription from promoters harboring its cis element at the upstream or downstream of TSS in a form of monomer. The cryo-EM structures of C. crescentus GcrA-bound transcription activation complexes, GcrA TAC(U) and GcrA TAC(D), reveal the interactions between GcrA, RNAP, sigma(70), and promoter DNA, as well as the disruption of sequence-specific interaction between GcrA and DNA depending on the location of GcrA cis elements relative to TSS.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Multidisciplinary Sciences
Kyle S. Skalenko, Lingting Li, Yuanchao Zhang, Irina O. Vvedenskaya, Jared T. Winkelman, Alexander L. Cope, Deanne M. Taylor, Premal Shah, Richard H. Ebright, Justin B. Kinney, Yu Zhang, Bryce E. Nickels
Summary: Chemical modifications of RNA 5'-ends allow epitranscriptomic regulation, impacting various aspects of RNA fate. In Escherichia coli cells, RNAs with a 5'-end hydroxyl are produced by primer-dependent transcription initiation using dinucleotide RNAs as primers. The study reveals that primer-dependent initiation in E. coli involves different dinucleotide primers and is influenced by promoter sequences surrounding the primer binding site.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Medicine, Research & Experimental
Gabriele Neumann
Summary: Reverse genetics has become a fundamental technique in many influenza virus laboratories, allowing for advancements in both basic and applied virology studies. This technology enables the study and revival of extinct influenza viruses, rapid characterization of new influenza strains, as well as the generation of traditional and novel influenza vaccines.
COLD SPRING HARBOR PERSPECTIVES IN MEDICINE
(2021)
Article
Virology
Yuan Li, Sarah Arcos, Kimberly R. Sabsay, Aartjan J. W. te Velthuis, Adam S. Lauring
Summary: The influenza virus polymerase plays a central role in the evolution of the virus. Mutations in the polymerase are necessary for the efficient spread of animal-derived viruses in human populations. The polymerase also determines the rate at which the virus acquires mutations that lead to drug resistance or antigenic drift. However, our understanding of the effects of mutations on the influenza RNA-dependent RNA polymerase (RdRp) is limited. In this study, deep mutational scanning of a specific protein in the polymerase was performed to understand the constraints and effects of mutations. The results provide valuable insights into the replication and evolution of the influenza virus.
JOURNAL OF VIROLOGY
(2023)
Article
Virology
Hana Veler, Haitian Fan, Jeremy R. Keown, Jane Sharps, Marjorie Fournier, Jonathan M. Grimes, Ervin Fodor
Summary: This study characterizes the interaction between the viral polymerase and Rab11a and identifies the important domains involved in this interaction. The findings provide insights into the cytoplasmic transport of vRNPs and suggest a potential target site for the development of influenza antiviral drugs.
JOURNAL OF VIROLOGY
(2022)
Review
Biochemistry & Molecular Biology
Alexander P. Walker, Ervin Fodor
TRENDS IN MICROBIOLOGY
(2019)
Article
Biochemistry & Molecular Biology
Nicole C. Robb, Aartjan J. W. te Velthuis, Ervin Fodor, Achillefs N. Kapanidis
NUCLEIC ACIDS RESEARCH
(2019)
Article
Multidisciplinary Sciences
Haitian Fan, Alexander P. Walker, Loic Carrique, Jeremy R. Keown, Itziar Serna Martin, Dimple Karia, Jane Sharps, Narin Hengrung, Els Pardon, Jan Steyaert, Jonathan M. Grimes, Ervin Fodor
Article
Chemistry, Medicinal
David C. McGowan, Wendy Balemans, Werner Embrechts, Magali Motte, Jeremy R. Keown, Christophe Buyck, Jordi Corbera, Mario Funes, Laura Moreno, Ludwig Cooymans, Abdellah Tahri, Julien Eymard, Bart Stoops, Rudy Strijbos, Joke Van den Berg, Ervin Fodor, Jonathan M. Grimes, Anil Koul, Tim H. M. Jonckers, Pierre Raboisson, Jerome Guillemont
JOURNAL OF MEDICINAL CHEMISTRY
(2019)
Article
Medicine, Research & Experimental
Ervin Fodor, Aartjan J. W. te Velthuis
COLD SPRING HARBOR PERSPECTIVES IN MEDICINE
(2020)
Article
Virology
Alexander P. Walker, Jane Sharps, Ervin Fpdor
JOURNAL OF VIROLOGY
(2020)
Article
Multidisciplinary Sciences
Loic Carrique, Haitian Fan, Alexander P. Walker, Jeremy R. Keown, Jane Sharps, Ecco Staller, Wendy S. Barclay, Ervin Fodor, Jonathan M. Grimes
Review
Microbiology
Aartjan J. W. te Velthuis, Jonathan M. Grimes, Ervin Fodor
Summary: RNA viruses, including important human and animal pathogens, have genomes consisting of single or multiple RNA segments. Replication and transcription are performed by RNA-dependent RNA polymerases, and recent high-resolution studies have provided insights into the structures of these enzymes and their roles in viral transcription and replication, offering potential targets for antiviral drug design.
NATURE REVIEWS MICROBIOLOGY
(2021)
Correction
Microbiology
Aartjan J. W. te Velthuis, Jonathan M. Grimes, Ervin Fodor
NATURE REVIEWS MICROBIOLOGY
(2021)
Article
Virology
Yue Xiao, Wenyu Zhang, Minglei Pan, David L. Bauer, Yuhai Bi, Mengmeng Cao, Ervin Fodor, Tao Deng
Summary: This study reveals the impact of subtype-specific noncoding regions on HA vRNA replication and virus growth phenotype in influenza A virus. The synergistic effect between the terminal noncoding regions and adjacent coding regions is important for optimal replication levels. These findings provide new insights into the regulation of RNA replication in multiple-segmented negative-strand RNA viruses.
JOURNAL OF VIROLOGY
(2021)
Article
Biochemical Research Methods
Michael L. Knight, Haitian Fan, David L. Bauer, Jonathan M. Grimes, Ervin Fodor, Jeremy R. Keown
Summary: The study presents the structure of the NP from an H3N2 virus, which is highly similar to NPs from other virus subtypes but with key differences, which may enhance understanding of the structural conservation of influenza NPs.
ACTA CRYSTALLOGRAPHICA SECTION F-STRUCTURAL BIOLOGY COMMUNICATIONS
(2021)
Article
Virology
Hana Veler, Haitian Fan, Jeremy R. Keown, Jane Sharps, Marjorie Fournier, Jonathan M. Grimes, Ervin Fodor
Summary: This study characterizes the interaction between the viral polymerase and Rab11a and identifies the important domains involved in this interaction. The findings provide insights into the cytoplasmic transport of vRNPs and suggest a potential target site for the development of influenza antiviral drugs.
JOURNAL OF VIROLOGY
(2022)
Article
Multidisciplinary Sciences
Jeremy R. Keown, Zihan Zhu, Loic Carrique, Haitian Fan, Alexander P. Walker, Itziar Serna Martin, Els Pardon, Jan Steyaert, Ervin Fodor, Jonathan M. Grimes
Summary: Influenza A viruses cause significant burdens to healthcare systems through seasonal epidemics and global pandemics. The viral RNA-dependent RNA polymerase plays a central role in the replication cycle of influenza viruses and is a potential target for antiviral development. By characterizing the inhibitory effect of nanobodies on the 1918 pandemic influenza virus polymerase complex, sensitive sites interfering with polymerase activity in vitro were identified, suggesting them as effective targets for potential influenza antiviral development.
NATURE COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Fangzheng Wang, Carol M. Sheppard, Bhakti Mistry, Ecco Staller, Wendy S. Barclay, Jonathan M. Grimes, Ervin Fodor, Haitian Fan
Summary: Host ANP32 proteins play a crucial role in influenza A virus genome replication by mediating the dimerization of the viral polymerase. The C-terminal low-complexity acidic region (LCAR) interacts with viral nucleoprotein (NP) and promotes NP recruitment to nascent RNA, ensuring co-replicative assembly of RNA into ribonucleoprotein complexes (RNPs).
NUCLEIC ACIDS RESEARCH
(2022)
Review
Biochemistry & Molecular Biology
Zihan Zhu, Ervin Fodor, Jeremy R. Keown
Summary: Influenza virus replication relies on the RNA-dependent RNA polymerase and viral ribonucleoprotein complex. Recent structural data have provided insights into the molecular mechanisms of influenza virus genome replication, particularly in terms of the encapsidation of nascent RNA, de novo assembly of ribonucleoprotein complexes, and the regulation of replication initiation through interactions with host and viral cues.
TRENDS IN MICROBIOLOGY
(2023)