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
Biochemistry & Molecular Biology
Yun-Sang Tang, Wai-Kin So, Ka-Leung Andy Ng, Ka-Pun Chris Mok, Pang-Chui Shaw
Summary: This study identified host heterogeneous nuclear ribonucleoprotein C as an interacting partner of influenza A virus nucleoprotein and confirmed its negative regulatory role in viral growth. The findings not only enhance our understanding of the influenza virus transmission mechanism but also provide a new research direction for the development of anti-influenza drugs.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Virology
Ramandeep Kaur, Jyoti Batra, Olga Stuchlik, Matthew S. Reed, Jan Pohl, Suryaprakash Sambhara, Sunil Kumar Lal
Summary: This study reveals that heterogeneous ribonucleoprotein A1 (hnRNPA1) interacts with the nucleoprotein (NP) of Influenza A virus (IAV) and affects viral replication. The findings suggest that cellular hnRNPA1 plays a protective role in the host and may serve as a potential target for antiviral therapeutics.
Article
Virology
Amol Patil, Darisuren Anhlan, Veronica Ferrando, Angeles Mecate-Zambrano, Alexander Mellmann, Viktor Wixler, Yvonne Boergeling, Stephan Ludwig
Summary: The phosphorylation of NS1 S205 in H1N1 virus is regulated by the cellular kinase CK2 and plays a significant role in viral replication in hosts. Phosphorylated NS1 S205 enhances viral polymerase activity by interacting efficiently with the host restriction factor DDX21, suggesting a potential target for antiviral intervention.
JOURNAL OF VIROLOGY
(2021)
Article
Immunology
Caiyue Ren, Tong Chen, Shishuo Zhang, Qingxia Gao, Jiahui Zou, Peng Li, Biaoxiong Wang, Yaxin Zhao, Aotian Ouyang, Sizhu Suolang, Hongbo Zhou
Summary: This study investigated the gene expression profiles in response to swine H1N1/2009 influenza A virus infection in newborn pig trachea cells. The researchers found that PLK3, a member of the PLK family, was upregulated after infection and played a crucial role in viral replication.
EMERGING MICROBES & INFECTIONS
(2023)
Article
Immunology
Qiao Wang, Qi Zhang, Maiqing Zheng, Jie Wen, Qinghe Li, Guiping Zhao
Summary: The study systematically investigated the physical interactions between 11 H5N1 avian influenza virus proteins and host proteins in chicken DF1 cells using AP-MS, revealing how the host machinery is manipulated during the course of H5N1 AIV infection. Over 1,000 interactions were identified involving 621 chicken proteins, providing a comprehensive understanding of the virus-host interactions.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Virology
Mengqi Yu, Yanna Guo, Lingcai Zhao, Yuanlu Lu, Qingzheng Liu, Yinjing Li, Lulu Deng, Zhiyu Shi, Haifeng Wang, Samar Dankar, Jihui Ping
Summary: The study found that two mutations in the NS1 protein of influenza A virus can alter the viral properties, increasing its replication ability and pathogenicity in the host, while inhibiting the host's immune response. These mutations may serve as potential targets for antiviral drugs and vaccine development.
Article
Chemistry, Medicinal
Chuanfeng Liu, Ying Zhang, Ping Li, Huinan Jia, Jiwei Zhang, Edeildo Ferreira da Silva-Junior, Sunanda Samanta, Parimal Kar, Bing Huang, Xinyong Liu, Peng Zhan
Summary: Compound IIB-2, identified through structural optimization, demonstrated comparable inhibitory effects on oseltamivir-resistant strains to its precursor compound A9, while exhibiting reduced toxicity. Further investigations revealed that compound IIB-2 impedes virus proliferation by blocking the export of influenza virus nucleoprotein.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Multidisciplinary Sciences
Shalabh Mishra, Athira S. Raj, Akhilesh Kumar, Ashwathi Rajeevan, Puja Kumari, Himanshu Kumar
Summary: The cytosolic DNA sensor IFI16 plays a crucial role in activating programmed cell death pathways in influenza A virus (IAV) infected cells by functioning as an RNA sensor for the virus. Its activation triggers the production of interferons and pro-inflammatory cytokines, promoting cell death and inflammatory responses.
Article
Multidisciplinary Sciences
Kelsey M. Haas, Michael J. Mcgregor, Mehdi Bouhaddou, Benjamin J. Polacco, Eun-Young Kim, Thong T. Nguyen, Billy W. Newton, Matthew Urbanowski, Heejin Kim, Michael A. P. Williams, Veronica V. Rezelj, Alexandra Hardy, Andrea Fossati, Erica J. Stevenson, Ellie Sukerman, Tiffany Kim, Sudhir Penugonda, Elena Moreno, Hannes Braberg, Yuan Zhou, Giorgi Metreveli, Bhavya Harjai, Tia A. Tummino, James E. Melnyk, Margaret Soucheray, Jyoti Batra, Lars Pache, Laura Martin-Sancho, Jared Carlson-Stevermer, Alexander S. Jureka, Christopher F. Basler, Kevan M. Shokat, Brian K. Shoichet, Leah P. Shriver, Jeffrey R. Johnson, Megan L. Shaw, Sumit K. Chanda, Dan M. Roden, Tonia C. Carter, Leah C. Kottyan, Rex L. Chisholm, Jennifer A. Pacheco, Maureen E. Smith, Steven J. Schrodi, Randy A. Albrecht, Marco Vignuzzi, Lorena Zuliani-Alvarez, Danielle L. Swaney, Manon Eckhardt, Steven M. Wolinsky, Kris M. White, Judd F. Hultquist, Robyn M. Kaake, Adolfo Garcia-Sastre, Nevan J. Krogan
Summary: This study provides a comprehensive network model of IAV infection in human cells, identifying functional host targets for pan-viral HDT. Key host proteins essential for IAV infection are revealed, and gene variants associated with severe influenza are discovered. Moreover, compounds targeting identified host factors suppress IAV replication and exhibit broad antiviral activity across influenza and coronavirus families.
NATURE COMMUNICATIONS
(2023)
Article
Virology
David Scheibner, Angele Breithaupt, Christine Luttermann, Claudia Blaurock, Thomas C. Mettenleiter, Elsayed M. Abdelwhab
Summary: Since 2014, there have been several global outbreaks of avian influenza virus (AIV) H5N8 of clade 2.3.4.4. The viruses in the 2015-2016 outbreak (H5N8-B) exhibited unusually high pathogenicity in wild and domestic ducks. This study found that the high virulence of H5N8-B in Pekin ducks could be attributed to multiple factors, including hemagglutinin (HA), neuraminidase (NA), nucleoprotein (NP), and nonstructural protein 1 (NS1). Compared to H5N8-A, H5N8-B possessed distinct genetic and biological properties, which contributed to its increased receptor-binding affinity, neuraminidase activity, interferon antagonism, and replication. These findings provide insight into the mechanism underlying the high virulence of HPAIV in Pekin ducks.
JOURNAL OF VIROLOGY
(2022)
Article
Virology
Tong Wang, Fanhua Wei, Zhimin Jiang, Jingwei Song, Chengye Li, Jinhua Liu
Summary: The NS1 protein of influenza A viruses was found to enhance virulence by antagonizing host innate anti-viral responses. It was identified that the 14-3-3 epsilon protein interacts with NS1 and prevents the expression of IFN-beta, thereby inhibiting the immune response.
Article
Virology
Valerie Le Sage, Jack P. Kanarek, Seema S. Lakdawala, Nara Lee
Summary: By introducing nucleotide changes to viral RNA, it is found that NP binding is susceptible to sequence alterations, and the changes can impact NP binding at both the mutated site and distal regions.
JOURNAL OF MEDICAL VIROLOGY
(2023)
Article
Virology
Yimeng Wang, Jianhong Zhou, Samuel G. Mackintosh, Yuchun Du
Summary: RuvBL2 protein interacts with the NS1 protein of IAV, and decreased levels of RuvBL2 in infected cells lead to apoptosis. The NS1 protein inhibits non-NS1 viral element-induced apoptosis by maintaining RuvBL2 abundance in infected cells.
Article
Medicine, Research & Experimental
Jiwon Jung, Sophia T. Mundle, Irina Ustyugova, Andrew P. Horton, Daniel R. Boutz, Svetlana Pougatcheva, Ponraj Prabakaran, Jonathan R. McDaniel, Gregory R. King, Daechan Park, Maria D. Person, Congxi Ye, Bing Tan, Yuri Tanno, Jin Eyun Kim, Nicholas C. Curtis, Joshua DiNapoli, Simon Delagrave, Ted M. Ross, Gregory C. Ippolito, Harry Kleanthous, Jiwon Lee, George Georgiou
Summary: Elderly individuals exhibit a diminished adaptive immune response to seasonal influenza vaccination, with an increase in cross reactive (CR) antibodies that recognize non-HA influenza proteins, particularly sulfated glycan antigens found in egg-produced vaccines. These unintended antibody responses may result in suboptimal immunity against influenza.
JOURNAL OF CLINICAL INVESTIGATION
(2021)
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)