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
Multidisciplinary Sciences
Scott P. Lyons, Elora C. Greiner, Lauren E. Cressey, Mark E. Adamo, Arminja N. Kettenbach
Summary: The PPP family is responsible for cellular serine and threonine dephosphorylation, achieving substrate specificity and selectivity by forming multimeric holoenzymes. Methylation plays a crucial role in regulating PPP holoenzyme assembly for PP2A, PP4, and PP6, with implications in human diseases like cancer and neurodegeneration. Endogenous PPP methylation is shown to have a crucial regulatory function in transformed and non-transformed cell lines in an isoform-specific manner.
SCIENTIFIC REPORTS
(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
Microbiology
Julianna Han, Ketaki Ganti, Veeresh Kumar Sali, Carly Twigg, Yifeng Zhang, Senthamizharasi Manivasagam, Chieh-Yu Liang, Olivia A. Vogel, Iris Huang, Shanan N. Emmanuel, Jesse Plung, Lillianna Radoshevich, Jasmine T. Perez, Anice C. Lowen, Balaji Manicassamy
Summary: It is well documented that influenza A viruses selectively package 8 distinct viral ribonucleoprotein complexes (vRNPs) into each virion, but the exact role of host factors in genome assembly is not fully understood. This study shows that Rab11a+ vesicles play a crucial role in the congregation and assembly of vRNPs, enabling specific genome assembly and production of infectious virus particles. However, in the absence of Rab11a, viral RNA segments fail to congregate properly, resulting in defects in virus assembly and increased production of non-infectious particles.
Article
Biochemistry & Molecular Biology
Priyanka Choudhury, Jens Kretschmer, Philipp Hackert, Katherine E. Bohnsack, Markus T. Bohnsack
Summary: RNA helicase DDX55 is predominantly localized in the nucleoplasm in human cells and associates with pre-ribosomal subunits, playing a crucial role in the maturation of large subunit pre-rRNAs. The C-terminal region of DDX55 is essential for its substrate specificity, recruitment to pre-ribosomes, and may target domain IV during LSU biogenesis.
Article
Multidisciplinary Sciences
Franziska Guenl, Tim Krischuns, Julian A. Schreiber, Lea Henschel, Marius Wahrenburg, Hannes C. A. Drexler, Sebastian A. Leidel, Vlad Cojocaru, Guiscard Seebohm, Alexander Mellmann, Martin Schwemmle, Stephan Ludwig, Linda Brunotte
Summary: The replication of influenza A virus relies on ubiquitination of the viral polymerase derived from host cells. This study reveals that site-specific ubiquitination of PB1-K578 is acquired during infection and regulates the dimerization of polymerase and the binding of NP. Mass spectrometry analysis has identified 59 modified lysines across the three subunits of the viral polymerase, which affect mRNA transcription, vRNA replication, and the generation of recombinant viruses via non-proteolytic mechanisms.
NATURE COMMUNICATIONS
(2023)
Article
Biochemistry & Molecular Biology
Xin Zhang, Mamun-Or Rashid, Tian-Yu Zhao, Yuan-Yuan Li, Meng-Jun He, Ying Wang, Da-Wei Li, Jia-Lin Yu, Cheng-Gui Han
Summary: The C-terminal truncation of P0 proteins compromises the systemic infection of BrYV and PLRV. While the truncation does not affect the local VSR activity of P0 proteins, the systemic infection cannot be rescued by transient or ectopic expression of VSR proteins. Additionally, systemic infection may be independent of the VSR activity of P0.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Virology
Saptarshi Banerjee, Aratrika De, Nandita Kedia, Koustav Bhakta, Linfa Wang, Bornali Bhattacharjee, Arindam Mondal
Summary: In this study, the researchers compared the RNA polymerases of bat influenza viruses and classical influenza A viruses (IAVs) and identified differential amino acid preferences in the PB2 subunit. They found that the PB2-282 residue, which is serine in bat viruses and glutamic acid in classical IAVs, affects the polymerase activity and replication efficiency of the virus in different host species. The results suggest that this residue may serve as a restriction element of the bat virus polymerase, limiting its activity in nonbat host species.
JOURNAL OF VIROLOGY
(2022)
Review
Biochemistry & Molecular Biology
Celia Jakob, Rithu Paul-Stansilaus, Martin Schwemmle, Roland Marquet, Hardin Bolte
Summary: The genome of influenza A virus consists of eight unique viral RNA segments, and reassortment events can create new IAVs. Recent research suggests that a viral genome packaging mechanism promotes reassortment by delivering the genome segments into the virus particle. However, there is a current shortage of functionally validated intersegmental RNA-RNA interactions in understanding this mechanism.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Biology
Daniel Flores-Mireles, Yolanda Camacho-Villasana, Madhurya Lutikurti, Aldo E. Garcia-Gurrerio, Guadalupe Lozano-Rosas, Victoria Chagoya, Emma Berta Gutierrez-Cirlos, Ulrich Brandt, Alfredo Cabrera-Orefice, Xochitl Perez-Martinez
Summary: The Cytb subunit of yeast mitochondrial complex bc is encoded in the mitochondrial genome and has eight transmembrane helices containing two hemes b. Cbp3 and Cbp6 assist in Cytb synthesis, while Cbp4 induces Cytb hemylation. Lack of Qcr7 reduces Cytb synthesis through an assembly-feedback mechanism involving Cbp3/Cbp6. Deletion of the Cytb C-region does not affect Cytb synthesis but disrupts the assembly-feedback regulation, resulting in non-respiratory mutants.
LIFE SCIENCE ALLIANCE
(2023)
Article
Biochemistry & Molecular Biology
Joanna Szpotkowska, Kamil Szpotkowski, Jerzy Ciesiolka
Summary: In this study, the spatial folding of the 5'-terminal region of mouse p53 mRNA was proposed using the SAXS method and the RNAComposer program. The RNA-assisted affinity chromatography technique was used to identify proteins that bind to this region. Most of the identified proteins were found to bind to the sites that are accessible for hybridization with complementary oligonucleotides. Additionally, hnRNP K and PCBP2 were found to have high binding affinity to the 5'-terminal region of mouse p53 mRNA.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Immunology
Anne Rosbjerg, Reinhard Wurzner, Peter Garred, Mikkel-Ole Skjoedt
Summary: Complement system activation relies on the interaction between pathogens and pattern recognition molecules, particularly through MASPs in the lectin pathway. This study found that MASPs can independently recognize certain fungal pathogens, such as the dangerous Aspergillus fumigatus, facilitating complement activation. MASPs were observed to have dual functions as enzymes and as PRMs, revealing a previously unknown pathway for complement activation.
JOURNAL OF INNATE IMMUNITY
(2021)
Article
Microbiology
Tim Krischuns, Catherine Isel, Petra Drncova, Maria Lukarska, Alexander Pflug, Sylvain Paisant, Vincent Navratil, Stephen Cusack, Nadia Naffakh
Summary: This study investigates the binding modes of the RNA-dependent RNA polymerases (FluPol) of influenza B viruses (IBVs) and influenza A viruses (IAVs) to the host RNA polymerase II (RNAP II). The findings suggest that IBVs and IAVs have evolved distinct binding interfaces to recruit the RNAP II, with IBVs using the PB2 627 subdomain for binding. This divergence in binding modes may represent avian- and human-optimized modes and has been shaped by the broader interaction network between the FluPol and the host transcriptional machinery.
Article
Microbiology
Erika Seshimo, Fumitaka Momose, Yuko Morikawa
Summary: The genome of the influenza A virus consists of eight segments of negative-strand RNA. In this study, researchers focused on identifying the essential sequence for selective packaging in the 5'-terminus of the sixth neuraminidase gene segment vRNA (Seg.6). Mutations in certain regions reduced infectious titers and eliminated mutant vRNAs through competitive packaging with wild-type vRNA. These regions were identified as the 5'-terminal packaging signal for the N1 subtype Seg.6 vRNA.
FRONTIERS IN MICROBIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Yunshan Zhang, Min Zhu, Jun Pan, Qunnan Qiu, Xinyu Tong, Xiaolong Hu, Chengliang Gong
Summary: It was found that BmCPV can produce vcircRNA_000048, which encodes a vsp21 to suppress viral replication. Vsp21 inhibits viral replication by inducing autophagy and activating the NF-κB signaling pathway. Vsp21 enhances the ubiquitination and degradation of phospho-IκB-α by interacting with UCH.
INSECT BIOCHEMISTRY AND MOLECULAR BIOLOGY
(2023)
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)