Article
Virology
Katinka Doehner, Angela Cornelius, Manutea Christophe Serrero, Beate Sodeik
Summary: This article highlights the key steps in herpesviral infection, including capsid stabilization during assembly, early interactions with host cells to ensure nuclear targeting, and genome uncoating. After fusion with a host membrane, capsids recruit microtubule motors for traveling to the centrosome, eventually reaching the nucleus. Capsid-associated tegument proteins interact with nucleoporins to facilitate injection of genomes into the nucleoplasm for transcription and replication, while some cell types may disarm or silence incoming capsids to prevent infection.
CURRENT OPINION IN VIROLOGY
(2021)
Correction
Multidisciplinary Sciences
Rosamaria Pennisi, Maria Musarra-Pizzo, Zhixiang Lei, Grace Guoying Zhou, Maria Teresa Sciortino
Summary: The paper has been amended and the revised version can be accessed through a link at the top of the paper.
SCIENTIFIC REPORTS
(2021)
Article
Virology
Nabil El Bilali, Bita Khadivjam, Eric Bonneil, Pierre Thibault, Roger Lippe
Summary: The study investigated the composition of HSV-1 A, B, and C nuclear capsids, identifying host proteins specific to C-capsids. By purifying viral particles using a novel method, it aims to uncover the differences and functional relevance of these viral capsids. This innovative approach opens up new research avenues to clarify the biology of herpesviruses.
JOURNAL OF VIROLOGY
(2021)
Article
Chemistry, Multidisciplinary
Stanislav Kler, Ran Zalk, Alexander Upcher, Idit Kopatz
Summary: This article reports a new type of nanoparticle with a capsid composed of three SV40 virus capsid proteins, which closely mimics the intracellular pathway of the virus and has potential applications in gene delivery.
Article
Virology
Soumya Sucharita, Kuan Zhang, Sylvia Van Drunen Littel-van den Hurk
Summary: Bovine herpesvirus-1 (BoHV-1) is a major pathogen in cattle causing rhinotracheitis and vulvovaginitis. The tegument protein VP8 plays a crucial role in viral replication and is phosphorylated by the viral kinase US3 for translocation. VP8 and VP22 are found to interact and co-localise in the primary enveloped virions, suggesting VP22's critical role in packaging VP8.
Article
Microbiology
Ethan C. M. Thomas, Renee L. Finnen, Jeffrey D. Mewburn, Stephen L. Archer, Bruce W. Banfield
Summary: The expression of HSV pUL16 and pUL21 proteins can prevent nucleocapsids from binding to nuclear pore complexes and delivering their genomes back to the nucleus. This finding provides important insights into the biology of herpes simplex virus.
Article
Immunology
Jie Ma, Jinjin Liu, Lijun Zheng, Chao Wang, Qingxia Zhao, Yuqi Huo
Summary: This study investigated the effects of N-and C-terminal sequence additions to the VP1 of a GII.4 NoV during its assembly into VLPs. The results showed that VP1 can tolerate foreign sequences without affecting its ability to assemble into VLPs.
MICROBIAL PATHOGENESIS
(2022)
Article
Immunology
Nur Firdaus Isa, Olivier Bensaude, Nadiah C. Aziz, Shona Murphy
Summary: The HSV-1 protein ICP22 interacts with cellular proteins to inhibit host cell gene expression and promote viral gene expression, affecting elongation of pol II through various checkpoints. ICP22 interacts with elongation regulators to inhibit transcription elongation of cellular genes. The viral activator VP16 competes with ICP22 to deliver elongation factors to viral genes.
Article
Microbiology
Vesa Aho, Sami Salminen, Salla Mattola, Alka Gupta, Felix Flomm, Beate Sodeik, Jens B. Bosse, Maija Vihinen-Ranta
Summary: Herpes simplex virus capsids are assembled in the nucleus and move by diffusion through the nucleoplasm to the nuclear envelope for egress. Changes in chromatin architecture during infection enhance nuclear diffusion of capsids at late infection, which is the rate-limiting step for the nuclear egress of the virus. Understanding the kinetics of capsid translocation in the nucleus is fundamental for DNA virus research.
Article
Immunology
Sukhada Kanse, Mehak Khandelwal, Rajan Kumar Pandey, Manoj Khokhar, Neetin Desai, Bajarang Vasant Kumbhar
Summary: This study used immune-informatics and molecular modeling methods to design a multi-epitope subunit vaccine targeting the VP1 protein of JC polyomavirus. Molecular dynamics simulation analysis showed that the vaccine formed a stable complex with the TLR4 receptor. This study has important implications for the development of a vaccine against JC polyomavirus.
Article
Microbiology
Tomasz H. Benedyk, Julia Muenzner, Viv Connor, Yue Han, Katherine Brown, Kaveesha J. Wijesinghe, Yunhui Zhuang, Susanna Colaco, Guido A. Stoll, Owen S. Tutt, Stanislava Svobodova, Dmitri I. Svergun, Neil A. Bryant, Janet E. Deane, Andrew E. Firth, Cy M. Jeffries, Colin M. Crump, Stephen C. Graham
Summary: The HSV-1 protein pUL21 functions as an adaptor for protein phosphatase 1 (PP1), directing the dephosphorylation of cellular and viral proteins. By antagonizing the activity of the virus-encoded kinase pUS3, pUL21 plays a crucial role in balancing kinase and phosphatase activities for optimal virus replication and spread.
Article
Virology
Carmen Elena Gonzalez, Nawel Ben Abdeljelil, Angela Pearson
Summary: UL24 of HSV-1 plays an important role in virus infection, and its C-terminal domain regulates its nuclear and cytoplasmic localization during infection. Mutations can enhance the accumulation of UL24 in the nucleus, and specific inhibitors can block the nuclear export of UL24.
Article
Biology
Bita Khadivjam, Eric Bonneil, Pierre Thibault, Roger Lippe
Summary: DDX3X is a mammalian RNA helicase that plays multiple roles in regulating RNA metabolism, cancers, innate immunity, and RNA viruses. This study reveals that herpes simplex virus 1 can redirect DDX3X to the nuclear envelope, where it modulates the exit of newly assembled viral particles. The depletion of DDX3X leads to the accumulation of virions in intranuclear herniations. Mechanistically, DDX3X interacts with the viral nuclear egress complex and stimulates the incorporation of pUS3, a viral kinase, in mature viral particles, thereby facilitating viral nuclear release. This research unveils the complex interaction between DDX3X and herpes simplex viruses, providing insights into viral propagation and potential targets for therapeutic intervention.
COMMUNICATIONS BIOLOGY
(2023)
Review
Immunology
Ruth F. Itzhaki
Summary: The research suggests that HSV1 may play a significant role in Alzheimer's disease in APOE-ε4 carriers, and further investigation into disease prevention through vaccination or prolonged antiviral treatment of HSV1 infection in APOE-ε4 carriers is warranted.
Article
Virology
Amber Vu, Shaowen White, Tiffany Cassmann, Richard J. Roller
Summary: Herpesvirus nuclear egress involves a regulated process coordinated by two virus proteins, with a heterodimeric nuclear egress complex (NEC) that drives budding of capsids at the inner nuclear membrane. Mutants with unregulated budding phenotype were studied, showing the significance of this regulation for virus replication and a structural requirement for nuclear lamina disruption.
JOURNAL OF VIROLOGY
(2021)
Article
Immunology
Celine Boutry, Andrew Hastie, Javier Diez-Domingo, Juan Carlos Tinoco, Chong-Jen Yu, Charles Andrews, Jean Beytout, Covadonga Caso, Huey-Shinn Cheng, Hee Jin Cheong, Eun Ju Choo, Dan Curiac, Emmanuel Di Paolo, Marc Dionne, Tamara Eckermann, Meral Esen, Murdo Ferguson, Wayne Ghesquiere, Shinn-Jang Hwang, Thiago Junqueira Avelino-Silva, Pavel Kosina, Chiu-Shong Liu, Jukka Markkula, Beate Moeckesch, Claudia Murta de Oliveira, Dae Won Park, Karlis Pauksens, Paola Pirrotta, Georg Plassmann, Carol Pretswell, Lars Rombo, Bruno Salaun, Johan Sanmartin Berglund, Isabelle Schenkenberger, Tino Schwarz, Meng Shi, Benita Ukkonen, Toufik Zahaf, Cristiano Zerbini, Anne Schuind, Anthony L. Cunningham
Summary: The efficacy against herpes zoster and immune responses to the adjuvanted recombinant zoster vaccine remained high for at least 7 years post-vaccination, with both efficacy and immune responses plateauing at high levels between 5.1 and 7.1 years post-vaccination. These results suggest that the clinical benefit of the vaccine in older adults is sustained long-term.
CLINICAL INFECTIOUS DISEASES
(2022)
Article
Hematology
Yandong Shen, Jane A. Freeman, Juliette Holland, Ann Solterbeck, Kartik Naidu, Asha Soosapilla, Paul Downe, Catherine Tang, Ian Kerridge, Lucinda Wallman, Nenna Van Bilsen, Vanessa Milogiannakis, Anouschka Akerman, Gabriela Martins Costa Gomes, Kerrie Sandgren, Anthony L. Cunningham, Stuart Turville, Stephen P. Mulligan
Summary: Chronic lymphocytic leukaemia (CLL) and monoclonal B-cell lymphocytosis (MBL) patients have poor immune response to COVID-19 vaccines, with most of them failing to produce sufficient antibody levels. The patients' treatment status and reduced immune function are associated with vaccine immunization failure.
BRITISH JOURNAL OF HAEMATOLOGY
(2022)
Article
Microbiology
Kevin Danastas, Ava Larsen, Sophie Jobson, Gerry Guo, Anthony L. Cunningham, Monica Miranda-Saksena
Summary: This study reveals the important role of actin and myosin V in the release of HSV-1 from axon termini. Inhibition of actin polymerization and myosin V significantly reduces the release of the virus. These findings contribute to our understanding of the mechanisms of HSV-1 transmission.
Article
Pathology
Andrew J. Colebatch, Chandra Adhikari, Russell J. Diefenbach, Robert V. Rawson, Peter M. Ferguson, Helen Rizos, Georgina V. Long, Stanley W. McCarthy, John F. Thompson, James S. Wilmott, Richard A. Scolyer
Summary: Blue nevi involving lymph nodes are benign and often misdiagnosed as metastatic melanoma. This study provides evidence that these blue nevi have a benign clinical behavior and probably represent so-called benign metastasis.
AMERICAN JOURNAL OF SURGICAL PATHOLOGY
(2022)
Article
Biotechnology & Applied Microbiology
John J. Park, Ashleigh Stewart, Mal Irvine, Bernadette Pedersen, Zizhen Ming, Matteo S. Carlino, Russell J. Diefenbach, Helen Rizos
Summary: Uveal melanoma, a rare eye cancer, lacks approved therapy for metastatic cases. This study found that the response of uveal melanoma cells to PKC inhibitors varied, and it was not related to the degree of PKC suppression or inhibition of downstream pathways. Instead, uveal melanoma cells showed complex, PKC-independent signaling pathways that contributed to their survival and resistance to targeted therapies.
CANCER GENE THERAPY
(2022)
Article
Multidisciplinary Sciences
Racha Arnous, Sana Arshad, Kerrie Sandgren, Anthony L. Cunningham, Nicole Carnt, Andrew White
Summary: This study aims to investigate the presence of tissue-resident memory T cells (T-RMs) in deeper layers of the healthy human conjunctiva. Using immunofluorescence microscopy, the researchers found CD69(+)T(RM) subsets in all layers of the conjunctiva, with higher densities in the adenoid layer. Interestingly, CD4 T-RMs were more abundant than CD8 T-RMs in the adenoid layer. These findings suggest the presence of defense mechanisms capable of inducing long-term immunogenic memory in the deep conjunctiva.
SCIENTIFIC REPORTS
(2022)
Article
Oncology
Russell J. Diefenbach, Jenny H. Lee, Ashleigh Stewart, Alexander M. Menzies, Matteo S. Carlino, Robyn P. M. Saw, Jonathan R. Stretch, Georgina V. Long, Richard A. Scolyer, Helen Rizos
Summary: This study developed a custom panel for detecting TERT promoter mutations in ctDNA from melanoma patients. Analysis of patient samples showed a high detection rate for BRAF, NRAS, and TERT promoter mutations, and the panel demonstrated consistency with tissue biopsies.
FRONTIERS IN ONCOLOGY
(2022)
Article
Chemistry, Medicinal
Jiadai Wu, Helen Power, Monica Miranda-Saksena, Peter Valtchev, Aaron Schindeler, Anthony L. Cunningham, Fariba Dehghani
Summary: This study identified potential antiviral compounds using computational methods and experimental evaluations, with one active compound showing a novel antiviral mechanism of action.
Article
Anesthesiology
Joon Hyung Kim, Robert Johnson, Martina Kovac, Anthony L. Cunningham, Mohamed Amakrane, Keith M. Sullivan, Alemnew F. Dagnew, Desmond Curran, Anne Schuind
Summary: Herpes zoster and HZ-associated pain significantly impact the quality of life of older and immunocompromised adults. The adjuvanted recombinant zoster vaccine has been proven effective in preventing HZ and reducing pain severity in healthy and immunocompromised adults. It also reduces the duration of HZ-associated pain and pain medication use, thus improving patients' quality of life.
Letter
Immunology
Kirstie M. Bertram, Thomas R. O'Neil, Erica E. Vine, Heeva Baharlou, Anthony L. Cunningham, Andrew N. Harman
Article
Medicine, General & Internal
Anouschka Akerman, Vanessa Milogiannakis, Tyra Jean, Camille Esneau, Mariana Ruiz Silva, Timothy Ison, Christina Fichter, Joseph A. Lopez, Deborah Chandra, Zin Naing, Joanna Caguicla, Daiyang Li, Gregory Walker, Supavadee Amatayakul-Chantler, Nathan Roth, Sandro Manni, Thomas Hauser, Thomas Barnes, Anna Condylios, Malinna Yeang, Maureen Wong, Charles S. P. Foster, Kenta Sato, Sharon Lee, Yang Song, Lijun Mao, Allison Sigmund, Amy Phu, Ann Marie Vande More, Stephanie Hunt, Mark Douglas, Ian Caterson, Warwick Britton, Kerrie Sandgren, Rowena Bull, Andrew Lloyd, Jamie Triccas, Stuart Tangye, Nathan W. Bartlett, David Darley, Gail Matthews, Damien J. Stark, Kathy Petoumenos, William D. Rawlinson, Ben Murrell, Fabienne Brilot, Anthony L. Cunningham, Anthony D. Kelleher, Anupriya Aggarwal, Stuart G. Turville
Summary: This study monitored the neutralization potency and breadth of antibodies against Omicron variants over time. The findings show that the antibody response to Omicron variants has been maturing, with increased breadth observed even to variants that were not yet in circulation.
Article
Biochemical Research Methods
Thomas R. O'Neil, Andrew N. Harman, Anthony L. Cunningham, Najla Nasr, Kirstie M. Bertram
Summary: Understanding the role of human immune cells in tissue is crucial. We developed a 24-color flow cytometry panel to analyze CD4(+) and CD8(+) tissue-resident memory T cells from human tissues. We carefully selected antibody clones and evaluated the effect of enzymatic digestion to ensure accurate marker expression.
Article
Multidisciplinary Sciences
Laura E. Downie, Xinyuan Zhang, Mengliang Wu, Senuri Karunaratne, Joon Keit Loi, Kirthana Senthil, Sana Arshad, Kirstie Bertram, Anthony L. Cunningham, Nicole Carnt, Scott N. Mueller, Holly R. Chinnery
Summary: The healthy human cornea contains immune cells that are commonly presumed to be dendritic cells, but the researchers found that many of these immune cells are actually lymphocytes. These corneal immune cells exhibit rapid, persistent motility and interact with other cells. The behavior of these immune cells can be altered in response to acute and chronic inflammatory stimuli, which can be modulated by therapeutic intervention.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Microbiology
Kevin Danastas, Gerry Guo, Jessica Merjane, Nathan Hong, Ava Larsen, Monica Miranda-Saksena, Anthony L. Cunningham
Summary: This study explores the effects of interferons (IFNs) on herpes simplex virus-1 (HSV-1) and reveals that IFNs have the potential to block virus release from nerve endings, thereby preventing transmission into the skin. The study also highlights the potential wider antiviral effects of IFN-γ in neurons, suggesting its role in HSV-1 reactivation. These findings identify new targets for the development of immunotherapies to impede HSV-1 spread from nerves to the skin.
Article
Medicine, Research & Experimental
Gabriel Duette, Bonnie Hiener, Hannah Morgan, Fernando G. Mazur, Vennila Mathivanan, Bethany A. Horsburgh, Katie Fisher, Orion Tong, Eunok Lee, Haelee Ahn, Ansari Shaik, Remi Fromentin, Rebecca Hoh, Charline Bacchus-Souffan, Najla Nasr, Anthony L. Cunningham, Peter W. Hunt, Nicolas Chomont, Stuart G. Turville, Steven G. Deeks, Anthony D. Kelleher, Timothy E. Schlub, Sarah Palmer
Summary: Through studying CD4(+) T cells of HIV-1 patients, the importance of effector memory T cells in the persistence of HIV-1 has been identified, and Nef has been suggested as a potential therapeutic target.
JOURNAL OF CLINICAL INVESTIGATION
(2022)