VIDO-InterVac

Permanent URI for this collection

https://hdl.handle.net/10388/12100

The Vaccine and Infectious Disease Organization-International Vaccine Centre (VIDO-InterVac) is a world leader in infectious disease research and vaccine development. With more than 150 personnel and over four decades of experience, the organization performs research on diseases that impact human and animal health. VIDO-InterVac is a research organization of the University of Saskatchewan and has some of the most advanced containment Level 2 and 3 facilities in the world.

Browse

Now showing 1 - 16 of 16

Bat adaptations in inflammation and cell death regulation contribute to viral tolerance
(American Society for Microbiology, 2025-02)
Bats are reservoirs for multiple viruses, some of which are known to cause global disease outbreaks. Virus spillovers from bats have been implicated in zoonotic transmission. Some bat species can tolerate viral infections, such as infections with coronaviruses and paramyxoviruses, better than humans and with less clinical consequences. Bat species are speculated to have evolved alongside these viral pathogens, and adaptations within the bat immune system are considered to be associated with viral tolerance. Inflammation and cell death in response to zoonotic virus infections prime human immunopathology. Unlike humans, bats have evolved adaptations to mitigate virus infection-induced inflammation. Inflammatory cell death pathways such as necroptosis and pyroptosis are associated with immunopathology during virus infections, but their regulation in bats remains understudied. This review focuses on the regulation of inflammation and cell death pathways in bats. We also provide a perspective on the possible contribution of cell death-regulating proteins, such as caspases and gasdermins, in modulating tissue damage and inflammation in bats. Understanding the role of these adaptations in bat immune responses can provide valuable insights for managing future disease outbreaks, addressing human disease severity, and improving pandemic preparedness.
Bat genomes illuminate adaptations to viral tolerance and disease resistance
(Nature, 2025-01) Morales, Ariadna E.; Dong, Yue; Brown, Thomas; Baid, Kaushal; Kontopoulos, Dimitrios-Georgios; Gonzalez, Victoria; Huang, Zixia; Ahmed, Alexis-Walid; Bhuinya, Arkadeb; Hilgers, Leon; Winkler, Sylke; Hughes, Graham; Li, Xiaomeng; Lu, Ping; Yang, Yixin; Kirilenko, Bogdan M.; Devanna, Paolo; Lama, Keon Wook; Nissan, Yomiran; Pippel, Martin; Davalos, Liliana M.; Vernes, Sonja C.; Puechmaille, Sebastien J.; Rossiter, Stephen J.; Yovel, Yossi; Prescott, Joseph B.; Kurth, Andreas; Ray, David A.; Kim, Burton K.; Myers, Eugene; Teeling, Emma C.; Banerjee, Arinjay; Irving, Aaron T.; Hiller, Michael
Zoonoses are infectious diseases transmitted from animals to humans. Bats have been suggested to harbour more zoonotic viruses than any other mammalian order1. Infections in bats are largely asymptomatic2,3, indicating limited tissue-damaging inflammation and immunopathology. To investigate the genomic basis of disease resistance, the Bat1K project generated reference-quality genomes of ten bat species, including potential viral reservoirs. Here we describe a systematic analysis covering 115 mammalian genomes that revealed that signatures of selection in immune genes are more prevalent in bats than in other mammalian orders. We found an excess of immune gene adaptations in the ancestral chiropteran branch and in many descending bat lineages, highlighting viral entry and detection factors, and regulators of antiviral and inflammatory responses. ISG15, which is an antiviral gene contributing to hyperinflammation during COVID-19 (refs. 4,5), exhibits key residue changes in rhinolophid and hipposiderid bats. Cellular infection experiments show species-specific antiviral differences and an essential role of protein conjugation in antiviral function of bat ISG15, separate from its role in secretion and inflammation in humans. Furthermore, in contrast to humans, ISG15 in most rhinolophid and hipposiderid bats has strong anti-SARS-CoV-2 activity. Our work reveals molecular mechanisms that contribute to viral tolerance and disease resistance in bats.
Combination therapy enhances the antiviral activity of IFN-λ against SARS-CoV-2 and MERS-CoV
(Elsevier, 2025-03) Rajabali Zadeh, Vahid; Lew, Jocelyne M.; Zahoor, Muhammad Atif; Santer, Deanna; Feld, Jordan J.; Falzarano, Darryl
Therapeutic options against pathogenic human coronaviruses remain limited. In a recent clinical trial, we demonstrated the therapeutic efficacy of pegylated-IFN-λ in COVID-19 outpatients. However, the emergence of variants that have the potential to evade IFN-mediated antiviral responses raises concerns regarding the continued efficacy of this approach. In this work, we compared the sensitivity of SARS-CoV-2 variants and MERS-CoV to IFN-λ treatment in vitro and explored the potential of combination therapy with other FDA-authorized or approved antiviral agents. We observed that in contrast to the ancestral strain, all other SARS-CoV-2 lineages showed varying, but increased resistance to IFN-λ treatment, from a 5.7-fold increase in EC50 value for the P.1 strain to a 32.7-fold increase for the B.1.1.7 variant. We further show that combination treatment with remdesivir or nirmatrelvir enhanced the antiviral effect of IFN-λ against both SARS-CoV-2 and MERS-CoV. These findings justify the initiation of further in vivo testing that ultimately can help inform the development of more effective therapeutic guidelines against pathogenic coronaviruses.
Combined immunoinformatic approaches with computational biochemistry for development of subunit-based vaccine against Lawsonia intracellularis
(PLoS One, 2025-02) Khatooni, Zahed; Broderick, Gordon; Anand, Sanjeev K.; Wilson, Heather
Lawsonia intracellularis (LI) are obligate intracellular bacteria and the causative agent of proliferative hemorrhagic enteropathy that significantly impacts the health of piglets and the profitability of the swine industry. In this study, we used immunoinformatic and computational methodologies such as homology modelling, molecular docking, molecular dynamic (MD) simulation, and free energy calculations in a novel three stage approach to identify strong T and B cell epitopes in the LI proteome. From ∼ 1342 LI proteins, we narrowed our focus to 256 proteins that were either not well-identified (unknown role) or were expressed at a higher frequency in pathogenic strains relative to non-pathogenic strains. At stage 1, these proteins were analyzed for predicted virulence, antigenicity, solubility, and probability of residing within a membrane. At stage 2, we used NetMHCPan4-1 to identify over ten thousand cytotoxic T lymphocyte epitopes (CTLEs) and 286 CTLEs were ranked as having high predicted binding affinity for the SLA-1 and SLA-2 complexes. At stage 3, we used homology modeling to predict the structures of the top ranked CTLEs and we subjected each of them to molecular docking analysis with SLA-1*0401 and SLA-2*0402. The top ranked 25 SLA–CTLE complexes were selected to be an input for subsequent MD simulations to fully investigate the atomic-level dynamics of proteins under the natural thermal fluctuation of water and thus potentially provide deep insight into the CTLE-SLA interaction. We also performed free energy evaluation by Molecular Mechanics/Poisson−Boltzmann Surface Area to predict epitope interactions and binding affinities to the SLA-1 and SLA-2. We identified the top five CTLEs having the strongest binding energy to the indicated SLAs (-305.6 kJ/mol, -219.5 kJ/mol, -214.8 kJ/mol, -139.5 kJ/mol and -92.6 kJ/mol, respectively.) W also performed B-cell epitope prediction and the top-ranked 5 CTLEs and 3 B-cell epitopes were organized into a multi-epitope subunit antigen vaccine construct joined using EAAAK, AAY, KK, and GGGGG linkers with 40 residues of the LI DnaK protein attached to the N-terminus to further enhance the antigenicity of the vaccine construct. Blind docking studies showed strong interactions between our vaccine construct with swine Toll-like receptor 5. Collectively, these molecular modeling and immunoinformatic analyses present a useful in silico protocol for the discovery of candidate antigen in many viral and bacterial pathogens.
Efficacy of a stable broadly protective subunit vaccine platform against SARS-CoV-2 variants of concern
(ScienceDirect, 2024-05) Garg, Ravendra; Liu, Qiang; Kessel, Jill Van; Asavajaru, Akarin; Uhlemann, Eva-Maria; Joessel, Morgane; Hamonic, Glenn; khatooni, zahed ; Kroeker, Andrea; Lew, Jocelyne; Scruten, Erin; Pennington, Paul; Deck, William; Prysliak, Tracy; Nickol, Michaela; Apel, Falko; Courant, Thomas; Kelvin, Alyson A.; Kessel, Andrew Van; Collin, Nicolas; Gerdts, Volker; Köster, Wolfgang; Falzarano, Darryl; Racine, Trina; Banerjee, Arinjay
The emergence and ongoing evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has highlighted the need for rapid vaccine development platforms that can be updated to counteract emerging variants of currently circulating and future emerging coronaviruses. Here we report the development of a “train model” subunit vaccine platform that contains a SARS-CoV-2 Wuhan S1 protein (the “engine”) linked to a series of flexible receptor binding domains (RBDs; the “cars”) derived from SARS-CoV-2 variants of concern (VOCs). We demonstrate that these linked subunit vaccines when combined with Sepivac SWE™, a squalene in water emulsion (SWE) adjuvant, are immunogenic in Syrian hamsters and subsequently provide protection from infection with SARS-CoV-2 VOCs Omicron (BA.1), Delta, and Beta. Importantly, the bivalent and trivalent vaccine candidates offered protection against some heterologous SARS-CoV-2 VOCs that were not included in the vaccine design, demonstrating the potential for broad protection against a range of different VOCs. Furthermore, these formulated vaccine candidates were stable at 2–8 °C for up to 13 months post-formulation, highlighting their utility in low-resource settings. Indeed, our vaccine platform will enable the development of safe and broadly protective vaccines against emerging betacoronaviruses that pose a significant health risk for humans and agricultural animals.
Expanding the bat toolbox: Carollia perspicillata bat cell lines and reagents enable the characterization of viral susceptibility and innate immune responses
(PLoS, 2025-04) Gonzalez, Victoria; Word, Cierra; Guerra-Pilaquinga, Nahomi; Mazinani, Mitra; Fawcett, Stephen; Portfors, Christine; Falzarano, Darryl; Kell, Alison M.; Jangra, Rohit K.; Banerjee, Arinjay; Seifert, Stephanie N.; Letko, Michael
Multiple viruses that are highly pathogenic in humans are known to have evolved in bats. How bats tolerate infection with these viruses, however, is poorly understood. As viruses engage in a wide range of interactions with their hosts, it is essential to study bat viruses in a system that resembles their natural environment like bat-derived in vitro cellular models. However, stable and accessible bat cell lines are not widely available for the broader scientific community. Here, we generated in vitro reagents for the Seba’s short-tailed bat (Carollia perspicillata), tested multiple methods of immortalization, and characterized their susceptibility to virus infection and response to immune stimulation. Using pseudotyped virus library and authentic virus infections, we show that these C. perspicillata cell lines derived from a diverse array of tissues are susceptible to viruses bearing the glycoprotein of numerous orthohantaviruses, including Andes and Hantaan virus and are also susceptible to live hantavirus infection. Furthermore, stimulation with synthetic double-stranded RNA prior to infection with vesicular stomatitis virus and Middle Eastern respiratory syndrome coronavirus induced a protective antiviral response, demonstrating the suitability of our cell lines to study the bat antiviral immune response. Taken together, the approaches outlined here will inform future efforts to develop in vitro tools for virology from non-model organisms and these C. perspicillata cell lines will enable studies on virus–host interactions in these bats.
Grouping Pig-Specific Responses to Mitogen with Similar Responder Animals may Facilitate the Interpretation of Results Obtained in an Out-Bred Animal Model
(J Vacc Vaccinol, 2014-04) Wilson, Heather; Pasternak, J. Alex; Ng, Siew Hon; Kaeser, Tobias; Meurens, Francois
Pig peripheral blood-derived mononuclear cells (PBMCs) and lamina propria mononuclear cells (LPMCs) stimulated with mitogens ex vivo can show significant animal-to-animal variation lead to difficulty in interpreting responses in an out-bred animal species. Mixed-cell populations were stimulated ex vivo with 2.5 μg/ml Con A or 2.5 ng/ml PMA plus 250 ng/ml ionomycin (PMAi; (LPCMs only)) or media alone for 72 hours. Supernatants were then tested for cytokine production using a Bioplex assay for porcine IFNα, IFNγ, IL-10, and IL-12. Unstimulated PBMCs had significant levels of IL-10 and the median value for this group decreased in the presence of Con A. Con A did, however, induce production of IFNα and IFNγ, but not IL-12 in this cell population. In contrast, unstimulated and Con A-stimulated LPMCs produced negligible IL-10, IFNα, IFNγ, and the majority of animals’ LPMCs showed negligible IL-12 production in response to Con A. In contrast, LPMCs stimulated with PMAi produced IFNγ suggesting cytokine production is mitogen–specific response. When we tracked animal-specific responses, we observed that discrete subsets of animal’s PBMCs responded to Con A with significantly increased or decreased IL-10 production relative to unstimulated cells. Further, in the LPMCs, some cells produced no IL-12 in response to Con A but showed augmented production in response to PMAi, while others showed production of IL-12 in response to Con A but no response to PMAi. Flow cytometric analysis showed that the PBMCs were a mixture of CD3+ T cells>CD21+ B cells>CD172+ myeloid cells whereas the LPMCs consisted of mainly Cytotoxic T cells and Natural Killer cells. The percentage of CD8α+CD4+ antigen-experienced T cells was greater in the LPMCs relative to the PBMCs. As expected in an out-bred species, animal-specific differences in cytokine production in response to stimulants exist and may confound interpretation of results unless tracked individually.
Highly pathogenic avian influenza H5N1: history, current situation, and outlook
(American Society for Microbiology, 2025-03-27) Krammer, Florian; Hermann, Enikő; Rasmussen, Angela
The H5N1 avian panzootic has resulted in cross-species transmission to birds and mammals, causing outbreaks in wildlife, poultry, and US dairy cattle with a range of host-dependent pathogenic outcomes. Although no human-to-human transmission has been observed, the rising number of zoonotic human cases creates opportunities for adaptive mutation or reassortment. This Gem explores the history, evolution, virology, and epidemiology of clade 2.3.4.4b H5N1 relative to its pandemic potential. Pandemic risk reduction measures are urgently required.
Longitudinal screening of retail milk from Canadian provinces reveals no detections of influenza A virus RNA (April–July 2024): leveraging a newly established pan-Canadian network for responding to emerging viruses
(Canadian Science Publishing, 2024-11-27) Wallace, Hannah L.; Wight, Jordan; Baz, Mariana; Dowding, Barbara; Flamand, Louis; Hobman, Tom; Jean, Francois; Joy, Jeffrey B.; Lang, Andrew S.; MacParland, Sonya; McCormick, Craig; Noyce, Ryan; Russell, Rodney S.; Sagan, Selena M.; Snyman, Jumari; Rzeszutek, Gabriela J.; Jafri, Mustafa S.; Bogoch, Issac; Kindrachuk, Jason; Rasmussen, Angela
Highly pathogenic avian influenza (HPAI) H5N1 has caused the deaths of more than 100 million birds since 2021, and human cases since 1997 have been associated with significant morbidity and mortality. Given recent detections of HPAI H5N1 in dairy cattle and H5N1 RNA detections in pasteurized retail milk in the United States, we established the pan-Canadian Milk Network in April 2024. Through our network of collaborators from across Canada, retail milk was procured longitudinally, approximately every 2 weeks, and sent to a central laboratory to test for the presence of influenza A virus RNA. Between 29 April and 17 July 2024, we tested 109 retail milk samples from all 10 Canadian provinces (NL, NS, PEI, NB, QC, ON, MB, SK, AB, and BC). All samples tested negative for influenza A virus RNA. This nationwide initiative was established for rapid retail milk screening as per the earliest reports of similar undertakings in the United States. Our independent testing results have aligned with reporting from federal retail milk testing initiatives. Despite no known HPAI infections of dairy cattle in Canada to date, H5N1 poses a significant threat to the health of both humans and other animals. By performing routine surveillance of retail milk on a national scale, we have shown that academic networks and initiatives can rapidly establish nationwide emerging infectious disease surveillance that is cost-effective, standardized, scalable, and easily accessible. Our network can serve as an early detection system to help inform containment and mitigation activities if positive samples are identified and can be readily reactivated should HPAI H5N1 or other emerging zoonotic viruses be identified in agricultural or livestock settings, including Canadian dairy cattle.
Protocol for mpox virus inactivation in containment level 3 for safe handling of animal samples
(ScienceDirect, 2025-06) Moni, Benedicte Mpia; Hurtado-Monzón, Arianna Mahely; Kessel, Jill Van; Kozak, Robert A.; Facciuolo, Antonio; Banerjee, Arinjay; Kumar, Anil
High biocontainment is required to handle infectious mpox virus (MPXV) specimens, which can hinder research and diagnostic efforts during outbreaks. Here, we present a protocol for inactivating MPXV-contaminated animal samples using commercial lysis buffers. We describe steps for virus propagation and quantification and MPXV inactivation. We then detail procedures for validating the inactivation using a cell-based technique and qPCR. This protocol provides a framework for safely managing MPXV in lower-containment laboratories, facilitating downstream applications and improved outbreak management.
SARS-CoV-2 3CLpro (main protease) regulates caspase activation of gasdermin-D/E pores leading to secretion and extracellular activity of 3CLpro
(Cell Press, 2024-12) Grin, Peter M.; Baid, Kaushal; de Jesus, Hugo C.R.; Kozarac, Nedim; Bell, Peter A.; Jiang, Steven Z.; Kappelhoff, Reinhild; Butler, Georgina S.; Leborgne, Nathan G.F.; Pan, Christina; Pablos, Isabel; Machado, Yoan; Vederas, John C.; Kim, Hugh; Benarafa, Charaf; Banerjee, Arinjay; Overall, Christopher M.
SARS-CoV-2 3C-like protease (3CLpro or Mpro) cleaves the SARS-CoV-2 polyprotein and >300 intracellular host proteins to enhance viral replication. By lytic cell death following gasdermin (GSDM) pore formation in cell membranes, antiviral pyroptosis decreases 3CLpro expression and viral replication. Unexpectedly, 3CLpro and nucleocapsid proteins undergo unconventional secretion from infected cells via caspase-activated GSDMD/E pores in the absence of cell lysis. Bronchoalveolar lavage fluid of wild-type SARS-CoV-2-infected mice contains 3CLpro, which decreases in Gsdmd−/−Gsdme−/− mice. We identify new 3CLpro cut-sites in GSDMD at LQ29↓30SS, which blocks pore formation by 3CLpro cleavage at LH270↓N lying adjacent to the caspase activation site (NFLTD275↓G). Cleavage inactivation of GSDMD prevents excessive pore formation, thus countering antiviral pyroptosis and increasing 3CLpro secretion. Extracellular 3CLpro retains activity in serum, dampens platelet activation and aggregation, and inactivates antiviral interferon-λ1. Thus, in countering gasdermin pore formation and pyroptosis in SARS-CoV-2 infection, 3CLpro is secreted with extracellular pathological sequelae.
SARS-CoV-2 Illumina GeNome Assembly Line (SIGNAL), a Snakemate workflow for rapid and bulk analysis of Illumina sequencing of SARS-CoV-2 genomes
(Oxford Academic, 2024-12) Nasir, Jalees A.; Maguire, Finlay; Smith, Kendrick M.; Panousis, Emily M.; Baker, Sheridan J. C.; Aftana, Patryk; Raphenya, Amogelang R.; Alcock, Brian P.; Maan, Hassaan; Knox, Natalie C.; Banerjee, Arinjay; Mossman, Karen; Wang, Bo; Simpson, Jared T.; Kozak, Robert A.; Mubareka, Samira; McArthur, Andrew G.
The incorporation of sequencing technologies in frontline and public health healthcare settings was vital in developing virus surveillance programs during the Coronavirus Disease 2019 (COVID-19) pandemic caused by transmission of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, increased data acquisition poses challenges for both rapid and accurate analyses. To overcome these hurdles, we developed the SARS-CoV-2 Illumina GeNome Assembly Line (SIGNAL) for quick bulk analyses of Illumina short-read sequencing data. SIGNAL is a Snakemake workflow that seamlessly manages parallel tasks to process large volumes of sequencing data. A series of outputs are generated, including consensus genomes, variant calls, lineage assessments and identified variants of concern (VOCs). Compared to other existing SARS-CoV-2 sequencing workflows, SIGNAL is one of the fastest-performing analysis tools while maintaining high accuracy. The source code is publicly available (github.com/jaleezyy/covid-19-signal) and is optimized to run on various systems, with software compatibility and resource management all handled within the workflow. Overall, SIGNAL illustrated its capacity for high-volume analyses through several contributions to publicly funded government public health surveillance programs and can be a valuable tool for continuing SARS-CoV-2 Illumina sequencing efforts and will inform the development of similar strategies for rapid viral sequence assessment.
SARS-CoV-2 pathogenesis in an angiotensin II–induced heart-on-a-chip disease model and extracellular vesicle screening
(PNAS, 2024-06) Wu, Qinghua; Rafatian, Naimeh; Wagner, Karl; Blamer, Jacob; Smith, Jacob; Okhovatian, Sargol; Aggarwal, Praful; Wang, Erika Yan; Banerjee, Arinjay; Zhao, Yimu; Nash, Trevor; Lu, Rick Xing Ze; Portillo-Esquivel, Luis Eduardo; Li, Chen Yu; Kuzmanov, Uros; Mandla, Serena; Virlee, Elizabeth; Landau, Shira; Lai, Benjamin Fook; Gramolini, Anthony; Liu, Chuan; Fleischer, Sharon; Veres, Teodor; Vunjak-Novakovic, Gordana; Zhang, Boyang; Mossman, Karen; Broeckel, Ulrich; Radisic, Milica
Adverse cardiac outcomes in COVID-19 patients, particularly those with preexisting cardiac disease, motivate the development of human cell-based organ-on-a-chip models to recapitulate cardiac injury and dysfunction and for screening of cardioprotective therapeutics. Here, we developed a heart-on-a-chip model to study the pathogenesis of SARS-CoV-2 in healthy myocardium established from human induced pluripotent stem cell (iPSC)-derived cardiomyocytes and a cardiac dysfunction model, mimicking aspects of preexisting hypertensive disease induced by angiotensin II (Ang II). We recapitulated cytopathic features of SARS-CoV-2-induced cardiac damage, including progressively impaired contractile function and calcium handling, apoptosis, and sarcomere disarray. SARS-CoV-2 presence in Ang II–treated hearts-on-a-chip decreased contractile force with earlier onset of contractile dysfunction and profoundly enhanced inflammatory cytokines compared to SARS-CoV-2 alone. Toward the development of potential therapeutics, we evaluated the cardioprotective effects of extracellular vesicles (EVs) from human iPSC which alleviated the impairment of contractile force, decreased apoptosis, reduced the disruption of sarcomeric proteins, and enhanced beta-oxidation gene expression. Viral load was not affected by either Ang II or EV treatment. We identified MicroRNAs miR-20a-5p and miR-19a-3p as potential mediators of cardioprotective effects of these EVs.
Studying bats using a One Health lens: bridging the gap between bat virology and disease ecology
(American Society for Microbiology, 2024-12) Gonzalez, Victoria; Hurtado-Monzón, Arianna M.; O'Krafka, Sabrina; Mühlberger, Elke; Letko, Michael; Frank, Hannah K.; Laing, Eric D.; Phelps, Kendra L.; Becker, Daniel J.; Munster, Vincent J.; Falzarano, Darryl; Schountz, Tony; Seifert, Stephanie N.; Banerjee, Arinjay
Accumulating data suggest that some bat species host emerging viruses that are highly pathogenic in humans and agricultural animals. Laboratory-based studies have highlighted important adaptations in bat immune systems that allow them to better tolerate viral infections compared to humans. Simultaneously, ecological studies have discovered critical extrinsic factors, such as nutritional stress, that correlate with virus shedding in wild-caught bats. Despite some progress in independently understanding the role of bats as reservoirs of emerging viruses, there remains a significant gap in the molecular understanding of factors that drive virus spillover from bats. Driven by a collective goal of bridging the gap between the fields of bat virology, immunology, and disease ecology, we hosted a satellite symposium at the 2024 American Society for Virology meeting. Bringing together virologists, immunologists, and disease ecologists, we discussed the intrinsic and extrinsic factors such as virus receptor engagement, adaptive immunity, and virus ecology that influence spillover from bat hosts. This article summarizes the topics discussed during the symposium and emphasizes the need for interdisciplinary collaborations and resource sharing.
Towards developing multistrain PEDV vaccines: Integrating basic concepts and SARS-CoV-2 pan-sarbecovirus strategies
(Virology, 2025-01) Fragoso-Saavedra, Mario; Liu, Qiang
Porcine epidemic diarrhea virus (PEDV) is a major pathogen impacting the global pig industry, with outbreaks causing significant financial losses. The genetic variability of PEDV has posed challenges for vaccine development since its identification in the 1970s, a problem that intensified with its global emergence in the 2010s. Since current vaccines provide limited cross-protection against PEDV strains, and the development of multistrain PEDV vaccines remains an underexplored area of research, there is an urgent need for improved vaccine solutions. The rapid development of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines and ongoing pan-sarbecovirus vaccine research, have demonstrated the potential of next-generation vaccine platforms and novel antigen design strategies. These advancements offer valuable insights for the development of multistrain PEDV vaccines. This review summarizes key aspects of PEDV virology and explores multistrain vaccine development considering SARS-CoV-2 vaccine innovations, proposing a framework for developing next-generation PEDV vaccine solutions.
Upregulation of porcine epidemic diarrhea virus (PEDV) RNA translation by the nucleocapsid protein
(Virology, 2024-11) Hao, Lin; Fragoso-Saavedra, Mario; Liu, Qiang
The role of coronaviral nucleocapsid (N) protein in regulating viral translation remains poorly understood. Here, we showed that the N protein of porcine epidemic diarrhea virus (PEDV) enhances the translation of both virus-like genomic RNA (gRNA) and messenger RNA. Further characterization of the gRNA translation upregulation showed that the N-terminal domain (NTD) + Linker region plays a major role. The stem-loop 1 in the 5′ untranslated region (UTR) and the budged stem loop in the 3′UTR are required for viral translation upregulation by PEDV N protein. The signaling kinase Akt exists in three isoforms. We found that Akt1 enhances viral gRNA translation upregulation by the N protein dependent on its kinase activity. We further showed an interaction between Akt1 and PEDV N, that is abolished by the NTD + Linker region. This suggested that the enhancing effect of Akt1 on translation upregulation by the N protein does not require interaction between these two proteins.

Browse

Browsing VIDO-InterVac by Title

Results Per Page

Sort Options