Biology subjects

Bhella, D.

Publications and source records attributed to Bhella, D..

18 recordsLinked to original sources

bioRxiv2026

Feline calicivirus encoding NanoLuc luciferase as a tool for assessing antibody neutralisation and antivirals

Feline calicivirus (FCV) is among the most common viruses to infect cats worldwide, with prevalence estimated to range from 10-90% depending on the population sampled. Typical FCV infection presents with oral ulcerations, fever and in some cases can also lead to clinical signs such as pneumonia or "limping syndrome". However, some FCV strains have been isolated from cats exhibiting virulent systemic (VS) disease, which is associated with high morbidity and mortality. Breakthrough VS-FCV infections have been recorded in vaccinated cats and, therefore, there is considerable interest in developing novel therapeutics for use in the face of VS-FCV outbreaks. However, to design effective therapeutics, a tractable system to systematically assess the efficacy of novel vaccine candidates or antivirals is required. Here, we used reverse genetics to develop an FCV reporter virus, inserting NanoLuc luciferase into the LC protein of FCV-Urbana (FCV-UrbanaNL). We characterised the replication kinetics of FCV-UrbanaNL in comparison to its parent virus and assessed the stability of the reporter over multiple passages. Subsequently, we developed virus neutralisation assays to assess a range of monoclonal antibodies that recognise FCV Urbana. We then assessed the breadth of neutralisation by exchanging the major capsid protein, VP1, of FCV Urbana with VP1 from the vaccine strain F9 and the VS-FCV strain NSW-E1. Finally, we evaluated the utility of the FCVNL reporter system to screen candidate antiviral compounds, identifying GS-441524 (the active metabolite of the parent nucleoside remdesivir) as having therapeutic potential against FCV. These findings highlight the potential of this reporter virus as a powerful molecular tool to accelerate the discovery and development of novel therapeutics.

microbiology↗

bioRxiv2026

Enhanced inter-chain hydrogen bonding in the murine norovirus VP1 capsid leads to increased particle stability and delayed viral uncoating

Capsid stability is vital for virion survival as the capsid must withstand varying environmental challenges such as pH and temperature to allow the virus to reach a target cell. Noroviruses are non-enveloped, icosahedral, positive-sense RNA viruses of importance to human health globally, with no approved vaccine or antiviral available. Despite this, the molecular mechanisms behind norovirus capsid stability and capsid rearrangement prior to RNA translocation are understudied. Using murine norovirus as a model, we utilised thermal stress to create a thermally stable virus population. By introducing three identified substitutions in the major capsid protein VP1 from this virus population into an infectious clone, we were able to create a heat and pH stable virus that had delayed viral uncoating during the infectious lifecycle. Cryo-EM reconstructions of the triple substitution virus demonstrated that enhanced inter-chain hydrogen bonding was vital for increased capsid stability. Finally, mutagenesis to remove the enhanced inter-chain hydrogen bonding reverted capsid stability back to wild-type levels. This work contributes to fundamental calicivirus biology by demonstrating areas of importance in capsid stability down to amino acid resolution. Furthermore, this work could inform vaccine design for a thermostable norovirus vaccine in the future. Author SummaryNoroviruses cause gastroenteritis and globally contribute to the death of up to 250,000 people worldwide per annum and an estimated healthcare cost of $4 billion. Despite this, there is no vaccine or antiviral treatment available, thus more work needs to be conducted to understand the mechanisms that underpin the viral life cycle. The norovirus capsid is a meta-stable shell-like structure evolved to protect the viral RNA from the harsh external environment, until cellular triggers allow genome release to initiate infection of a host cell. However, the molecular interactions that are key for controlling this balance are relatively unstudied. In this report, we identify that hydrogen bonding at the capsid protomer-protomer interface are vital for maintaining this balance, with increased inter-molecular hydrogen bonding at three specific amino acids able to increase viral stability whilst still permitting infectious genome release. Furthermore, reducing inter-molecular hydrogen bonding at these crucial amino acids was able to reverse this mechanism. These results should inform future norovirus vaccine studies, where thermostable virus-like-particles are needed to overcome issues with cold-chain storage.

microbiology↗

bioRxiv2026

Molecular architecture of Influenza A virions

Influenza A viruses (IAV) are clinically important pathogens that cause seasonal epidemics and pandemics in humans. IAV produce pleomorphic, enveloped virions, which can range from a spherical or bacilliform morphology, the predominant form in the most commonly studied laboratory strains, to long filamentous virions which are characteristic of clinical and veterinary isolates. Understanding the structure and function of filamentous virions is crucial for clarifying their role in viral persistence and immune evasion, and for informing the development of therapeutics that target their entry and/or egress pathways. Structural characterisation of influenza virions is challenging however owing to their fragility, heterogeneity and compared to most virus particles, unusually large size. Here, we combined structural and compositional approaches with integrative modelling to define the complete molecular architecture of influenza virions. In doing so we provide the first description of distinctive structural features of IAV filaments, including the selective incorporation of lipids, specific enrichment of viral and host proteins, and a viral cytoskeleton including a secondary helical layer within the viral capsid and extended fibrils of cofilactin. Collectively our findings suggest an important regulatory role for cofilactin in driving filament morphogenesis and provide important insights into the organisation and composition of IAV filamentous virions.

microbiology↗

bioRxiv2026

Cryo-EM of a Divergent Herpesvirus Reveals Structural Conservation and Novelty Including a Portal-Vertex Tegument Protein with Multiple Macrodomain-like Folds

Ictalurid herpesvirus 1 (channel catfish virus) is an evolutionarily distant relative of human herpesviruses, from which it is thought to have diverged >400M years ago. Using cryogenic electron microscopy (cryo-EM) combined with symmetry-breaking and particle subtraction approaches, we determined structures of both the immature capsid and virion of IcHV-1. Due to limited genome annotation, we used the machine learning-based tool ModelAngelo for de novo model building, enabling unambiguous protein identification even at marginal resolutions. Notably, the IcHV-1 virion was found to have a substantial and elaborate portal-vertex associated tegument (PVAT) complex. Overall, we determined the identities and structures of ten IcHV-1 proteins: the major capsid protein; the triplex proteins; two novel virion-associated inner tegument proteins; the portal protein; and a further four PVAT proteins. Our findings reveal a high degree of fold conservation in the core capsid proteins when compared with those of human herpesviruses, but also considerable structural novelty, including for the first time in a herpesvirus, identification of a protein that has four putative macrodomains.

microbiology↗

bioRxiv2025

Substrate-enhanced filamentation of 3-methylcrotonyl-CoA carboxylase in Legionella pneumophila

3-Methylcrotonyl-CoA carboxylase (MCC) is a biotin-dependent carboxylase that metabolizes the amino acid leucine. MCC is present in bacteria, fungi, plants, and animals. In humans, its overexpression is linked to cancer, and its deficiency is linked to inborn errors of metabolism with severe consequences, so understanding its structure and function has far reaching implications. Here, we explore the MCC from Legionella pneumophila, a pathogenic bacterium with a biphasic life cycle. Our endogenous holoenzyme yielded the highest resolution cryo-EM structure of MCC to date, allowing for identification of protein components by the machine learning tool ModelAngelo, confirmed independently by mass spectrometry. We also observed, for the first time, enhanced filamentation of MCC upon substrate binding. We propose that this filamentation, previously observed in the eukaryotes, but not in bacteria, may be important for cellular processes such as differentiation of life cycle or cell division.

biochemistry↗

bioRxiv2025

Identification of a novel structural motif and overexpression of key transcripts elucidated in Adenovirus 10

Adenoviruses are widely used as vectors for subunit vaccines and oncolytic therapies. Efficient vectors must infect target cells and deliver therapeutic transgenes at high levels. Species D adenoviruses, such as human adenovirus type 10 (HAdV-D10), are promising candidates due to low seroprevalence in humans. Here, we present the cryo-electron microscopy structure of the HAdV-D10 capsid alongside transcriptomic profiling of infected cells to inform vector development. The fiber shaft, essential for cell entry, was resolved at 4.6 [A], revealing a previously uncharacterized umbrella motif. Viral transcript analysis using an ORF-centric pipeline uncovered key differences from HAdV-C5, including abundant expression of a transcript encoding a protein equivalent to mature protein VII. These findings highlight the importance of detailed vector characterization prior to clinical translation and support the advancement of HAdV-D10 as a next-generation platform for gene delivery and vaccine development.

microbiology↗

bioRxiv2022

Ultrastructural characterization of a viral RNA and G-protein containing, membranous organelle formed in respiratory syncytial virus infected cells

Withdrawal statementThe authors have withdrawn their manuscript because since deposition of this preprint, they have become aware of the possibility that the findings reported may be an artefact. Carter et al. (J Struct Biol 2018 Jan;201(1):15-25. doi: 10.1016/j.jsb.2017.10.009) have reported that multilamellar bodies exhibit autofluorescence under cryogenic conditions. Thus, there is a possibility that stress induced by virus infection may stimulate formation of the features reported in this article, and autofluorescence, rather than specific labelling led them to identify the puncta as compartments containing RSV proteins or genomes. They are working to address these issues. Therefore, the authors do not wish this work to be cited as reference for the project. If you have any questions, please contact the corresponding author.

microbiology↗

bioRxiv2021

A global map of the Zika virus phosphoproteome reveals host-driven regulation of viral budding

Flaviviruses are enveloped, positive-strand RNA viruses that cause millions of infections in the human population annually. Although Zika virus (ZIKV) had been detected in humans as early as the 1950s, its reemergence in South America in 2015 resulted in a global health crisis. While flaviviruses encode 10 proteins that can be post-translationally modified by host enzymes, little is known regarding post-translational modifications (PTMs) of the flavivirus proteome. We used mass spectrometry to comprehensively identify host-driven PTMs on the ZIKV proteome. This approach allowed us to identify 43 PTMs across 8 ZIKV proteins, including several that are highly conserved within the Flavivirus genus. Notably, we found two phosphosites on the ZIKV envelope protein that are functionally important for viral propagation. Both appear to regulate viral budding, while one also impacts ZIKV cytopathogenicity. Additionally, we discovered host kinases that interact with ZIKV proteins and determined that Bosutinib--an FDA-approved tyrosine kinase inhibitor that targets some of these host kinases--impairs ZIKV growth, in part by blocking phosphorylation of a tyrosine residue on the envelope protein. Thus, we have defined a high-resolution map of host-driven PTMs on ZIKV proteins as well as cellular interacting kinases, uncovered novel mechanisms of host driven-regulation of ZIKV budding and cytopathogenicity, and identified an FDA-approved inhibitor of ZIKV growth.

microbiology↗

bioRxiv2021

Generation of chimeric respiratory viruses with altered tropism by coinfection of influenza A virus and respiratory syncytial virus

Interactions between respiratory viruses impact viral transmission dynamics and clinical outcomes. To identify and characterize virus-virus interactions at the cellular level, we coinfected human lung cells with influenza A virus (IAV) and respiratory syncytial virus (RSV). Super-resolution microscopy, live-cell imaging, scanning electron microscopy, and cryo-electron tomography revealed extracellular and membrane-associated filamentous structures consistent with hybrid viral particles (HVPs). We show that HVPs harbor surface glycoproteins and ribonucleoproteins of IAV and RSV, and use the RSV fusion glycoprotein to evade anti-IAV neutralising antibodies and to infect and spread among cells lacking IAV receptors. Finally, we show evidence of IAV and RSV coinfection within cells of the bronchial epithelium, with viral proteins from both viruses co-localising at the apical surface. Our observations have profound implications for infection biology as they define a previously unknown interaction between respiratory viruses that might affect virus pathogenesis by expanding virus tropism and facilitating immune evasion.

microbiology↗

bioRxiv2021

Helical Ordering of Envelope Associated Proteins and Glycoproteins in Respiratory Syncytial Virus Filamentous Virions

Human respiratory syncytial virus (RSV) causes severe respiratory illness in children and the elderly. Treatments for RSV disease are however limited and efforts to produce an effective vaccine have so far been unsuccessful. Understanding RSV virion structure is an important prerequisite for developing interventions to treat or prevent infection but has been challenging because of the fragility of virions propagated in cell culture. Here we show, using cryogenic electron microscopy (cryoEM) and cryogenic electron tomography (cryoET) of RSV particles cultivated directly on transmission electron microscopy (TEM) grids, that there is extensive helical symmetry in RSV filamentous virions. We have calculated a 16 [A] resolution three-dimensional reconstruction of the viral envelope, targeting the matrix protein (M) that forms an endoskeleton below the viral membrane. These data define a helical lattice of M proteins, showing how M is oriented relative to the viral envelope and that helical ordering of viral glycoproteins that stud the viral envelope is coordinated by the M layer. Moreover, the helically ordered viral glycoproteins in RSV filamentous virions cluster in pairs, which may have implications for the conformation of fusion (F) glycoprotein epitopes that are the principal target for vaccine and monoclonal antibody development. We also report the presence, in authentic virus infections, of N-RNA rings packaged within RSV filamentous virions. Overall, the structural data obtained provides molecular insight into the organization of the virion and the mechanism of its assembly.

microbiology↗

bioRxiv2021

The cryo-EM structure of vesivirus 2117 highlights functional variations in entry pathways for viruses in different clades of the vesivirus genus.

Vesivirus 2117 is an adventitious agent that has been responsible for lost productivity in biopharmaceutical production following contamination of Chinese hamster ovary cell cultures in commercial bioreactors. A member of the Caliciviridae, 2117 is classified within the Vesivirus genus in a clade that includes canine and mink caliciviruses but is distinct from the vesicular exanthema of swine clade, which includes the extensively studied feline calicivirus (FCV). We have used cryogenic electron microscopy (cryo-EM) to determine the structure of the capsid of this small, icosahedral, positive-sense RNA containing virus. We show that the outer face of the dimeric capsomeres, which contains the receptor binding site and major immunodominant epitopes in all caliciviruses studied thus far, is quite different from that of FCV. This is a consequence of a 22 amino-acid insertion in the sequence of the FCV major capsid protein that forms a cantilevered arm, which plays an important role in both receptor engagement and undergoes structural rearrangements thought to be important for genome delivery to the cytosol. Our data highlight a potentially important difference in the attachment and entry pathways employed by the different clades of the Vesivirus genus.

microbiology↗

bioRxiv2020

Higher-order structures of the foot-and-mouth disease virus RNA-dependent RNA polymerase required for dynamic inter-molecular interactions involved in viral genome replication

Replication of many positive-sense RNA viruses occurs within intracellular membrane-associated compartments. These are believed to provide a favourable environment for replication to occur, concentrating essential viral structural and non-structural components, as well as protecting these components from host-cell pathogen recognition and innate immune responses. However, the details of the molecular interactions and dynamics within these structures is very limited. One of the key components of the replication machinery is the RNA-dependent RNA polymerase, RdRp. This enzyme has been shown to form higher-order fibrils in vitro. Here, using the RdRp from foot-and-mouth disease virus (termed 3Dpol), we report fibril structures, solved at ~7-9 [A] resolution by cryo-EM, revealing multiple conformations of a flexible assembly. Fitting high-resolution coordinates led to the definition of potential intermolecular interactions. We employed mutagenesis using a sub-genomic replicon system to probe the importance of these interactions for replication. We use these data to propose models for the role of higher order 3Dpol complexes as a dynamic scaffold within which RNA replication can occur.

microbiology↗

bioRxiv2020

In situ structure determination of virus capsids imaged within cell nuclei by correlative light and cryo-electron tomography.

Cryo electron microscopy (cryo-EM), a key method for structure determination involves imaging purified material embedded in vitreous ice. Images are then computationally processed to obtain three-dimensional structures at atomic resolution. There is increasing interest in extending structural studies by cryo-EM into the cell, where biological structures and processes may be imaged in context. The limited penetrating power of electrons prevents imaging of thick specimens (>500 nm) however. Cryo-sectioning methods employed to overcome this are technically challenging, subject to artefacts or involve specialised equipment of limited availability. Here we describe the first structure of herpesvirus capsids determined by sub-tomogram averaging from nuclei of eukaryotic cells, achieved by cryo-electron tomography (cryo-ET) of re-vitrified cell sections prepared using the Tokuyasu method. Our reconstructions reveal that the capsid associated tegument complex is present on capsids prior to nuclear egress. We show that this approach to cryogenic imaging of cells is suited to both correlative light/electron microscopy and 3D structure determination.

biophysics↗

bioRxiv2019

Heterologous Expression of Human Norovirus GII.4 VP1 Leads to Assembly of T=4 Virus-Like Particles

Human noroviruses are a leading cause of acute gastroenteritis, yet there are still no vaccines or antivirals available. Expression of the norovirus capsid protein (VP1) in insect cells typically results in the formation of virus-like particles (VLPs) that are morphologically and antigenically comparable to native virions. Previous structural analysis of norovirus VLPs showed that the capsid has a T=3 icosahedral symmetry and is composed of 180 copies of VP1 that are folded into three quasi-equivalent subunits (A, B, and C). In this study, we determined the cryo-EM VLP structures of two GII.4 variants, termed CHDC-1974 and NSW-2012. Surprisingly, we found that greater than 95% of these GII.4 VLPs were larger than virions and 3D reconstruction showed that these VLPs exhibited T=4 icosahedral symmetry. We found that the T=4 VLPs showed several structural differences to the T=3 VLPs. The T=4 particles assemble from 240 copies of VP1 that adopt four quasi-equivalent conformations (A, B, C, and D) that form two distinct dimers, A/B and C/D. The T=4 protruding domains were elevated [~]21-[A] off the capsid shell, which was [~]7-[A] more than the previously studied GII.10 T=3 VLPs. A small cavity and flap-like structure at the icosahedral twofold axis disrupted the contiguous T=4 shell, a consequence of the D-subunit S-domains having smaller contact interfaces with neighboring dimers. Overall, our findings that old and new GII.4 VP1 sequences assemble T=4 VLPs might have implications for the design of potential future vaccines.\n\nIMPORTANCEThe discovery that the GII.4 VLPs have a T=4 symmetry is of significance, since this represents the first known T=4 calicivirus structure. Interestingly, the GII.4 2012 variant shares 96% amino acid identity with a current GII.4 VLP vaccine candidate sequence, which suggests that this vaccine might also have a T=4 symmetry. Our previous results with these GII.4 VLPs showed functional binding properties to antibodies and Nanobodies that were raised against T=3 (GII.10) VLPs. This suggests that the T=4 VLPs were antigenically comparable to T=3 particles, despite the obvious structural and size differences. On the other hand, these larger T=4 VLPs with novel structural features and possibly new epitopes might elicit antibodies that do not recognize equivalent epitopes on the T=3 VLPs. Further structural and binding studies using a library of GII.4-specific Nanobodies are planned in order to precisely investigate whether new epitopes are formed.

molecular biology↗

bioRxiv2018

Calicivirus VP2 forms a portal to mediate endosome escape

To initiate the infectious process, many viruses enter their host cells by triggering endocytosis following receptor engagement. The mechanism by which non-enveloped viruses, such as the caliciviruses, escape the endosome is however poorly understood. The Caliciviridae include many important human and animal pathogens, most notably norovirus, the cause of winter vomiting disease. Here we show that VP2, a minor capsid protein encoded by all caliciviruses, forms a large portal assembly at a unique three-fold symmetry axis following receptor engagement. This feature surrounds an open pore in the capsid shell. We hypothesise that the VP2 portal complex is the means by which the virus escapes the endosome, pene-trating the endosomal membrane to release the viral genome into the cytoplasm. Cryogenic electron microscopy (cryoEM) and asymmetric reconstruction were used to investigate structural changes in the capsid of feline calicivirus (FCV) that occur when the virus binds to its cellular receptor junctional adhesion molecule-A (fJAM-A). Near atomic-resolution structures were calculated for the native virion alone and decorated with soluble receptor fragments. We present atomic models of the major capsid protein VP1 in the presence and absence of fJAM-A, revealing the contact interface and conformational changes brought about by the interaction. Furthermore, we have calculated an atomic model of the portal protein VP2 and revealed the structural changes in VP1 that lead to pore formation. While VP2 was known to be critical for the production of infectious virus, its function has been hitherto undetermined. Our finding that VP2 assembles a portal that is likely responsible for endosome escape represents a major step forward in our understanding of both the Caliciviridae and icosahedral RNA containing viruses in general.

microbiology↗

bioRxiv2018

Structure of the Macrobrachium rosenbergii Nodavirus: A new genus within the Nodaviridae?

Macrobrachium rosenbergii nodavirus (MrNV) is a pathogen of freshwater prawns that poses a threat to food-security and causes significant economic losses in the aquaculture industries of many developing nations. A detailed understanding of the MrNV virion structure will inform the development of strategies to control outbreaks. The MrNV capsid has also been engineered to display heterologous antigens, thus knowledge of its atomic resolution structure will benefit efforts to develop tools based on this platform. Here we present an atomic-resolution model of the MrNV capsid protein, calculated by cryogenic electron microscopy (cryoEM) of MrNV virus-like particles (VLPs) produced in insect cells, and three-dimensional image reconstruction at 3.3 [A] resolution. CryoEM of MrNV virions purified from infected freshwater prawn post-larvae yielded a 6.6 [A] resolution structure confirming the biological relevance of the VLP structure.\n\nOur data revealed that unlike other known nodaviruses structures, which have been shown to assemble capsids having trimeric spikes, MrNV assembles a T=3 capsid with dimeric spikes. We also found a number of surprising similarities between the MrNV capsid structure and that of the Tombusviridae. 1. An extensive network of N-terminal arms lines the capsid interior forming long-range interactions to lace together asymmetric units. 2. The capsid shell is stabilised by three pairs of Ca2+ ions in each asymmetric unit. 3. The protruding spike domain exhibits a very similar fold to that seen in the spikes of the tombusviruses. These structural similarities raise questions concerning the correct taxonomic classification of MrNV.

microbiology↗

bioRxiv2018

Structure of the herpes-simplex virus portal-vertex

Herpesviruses include many important human pathogens such as herpes simplex virus, cytomegalovirus, varicella-zoster virus and the oncogenic Epstein-Barr virus and Kaposi-sarcoma associated herpesvirus. Herpes virions contains large icosahedral capsids that have a portal at a unique five-fold vertex, similar to that seen in the tailed bacteriophages. The portal is a molecular motor through which the viral genome enters the capsid during virion morphogenesis. The genome also exits the capsid through the portal-vertex when it is injected through the nuclear-pore into the nucleus of a new host cell to initiate infection. Structural investigations of the herpesvirus portal-vertex have proven challenging, owing to the small size of the tail-like portal-vertex associated tegument (PVAT), and the dense tegument layer that lays between the nucleocapsid and the viral envelope, obscuring the view of the portal-vertex. Here we show the structure of the herpes simplex virus portal-vertex at sub-nanometer resolution, solved by electron cryomicroscopy (cryoEM) and single-particle 3D reconstruction. This led to a number of new discoveries including the presence of two previously unknown portal associated structures that occupy the sites normally taken by the penton and the Ta triplex. Our data revealed that the PVAT is composed of ten copies of the C-terminal domain of pUL25, which are uniquely arranged as two tiers of star-shaped density. Our 3D reconstruction of the portal-vertex also shows that one end of the viral genome extends outside the portal in the manner described for some bacteriophage but not previously seen in any eukaryote viruses. Finally, we show that the viral genome is consistently packed in a highly-ordered left-handed spool to form concentric shells of DNA. Our data provide new insights into the structure of a molecular machine critical to the biology of an important class of human pathogens.

microbiology↗

bioRxiv2017

Cryo-Electron Microscopy Structure of the Macrobrachium Rosenbergii Nodavirus Capsid at 7 Angstroms Resolution

White tail disease in the giant freshwater prawn Macrobrachium rosenbergii causes significant economic losses in shrimp farms and hatcheries and poses a threat to food-security in many developing countries. Outbreaks of Macrobrachium rosenbergii nodavirus (MrNV), the causative agent of white tail disease (WTD) are associated with up to 100% mortality rates. Recombinant expression of the capsid protein of MrNV in insect cells leads to the production of VLPs closely resembling the native virus. We have investigated the structure of MrNV VLPs by cryogenic electron microscopy, determining a structure of the viral capsid at 7 angstroms resolution. Our data show that MrNV VLPs package nucleic acids in a manner reminiscent of other known nodavirus structures. The structure of the capsid however shows striking differences from insect and fish infecting nodaviruses, which have been shown to assemble trimer-clustered T=3 icosahedral virus particles. MrNV particles have pronounced dimeric blade-shaped spikes extending up to 6 nm from the outer surface of the capsid shell. Our structural analysis supports the assertion that MrNV along with the related virus of marine shrimp Penaeus vannamei nodavirus (PvNV) may represent a new genus of the Nodaviridae.\n\nAuthor summaryMacrobrachium rosenbergii nodavirus (MrNV) is the causative agent of white tail disease (WTD) which leads to 100% mortality in shrimp-farms growing giant freshwater prawn (M. rosenbergii). MrNV is therefore a significant threat to food security and causes severe economic losses in developing countries such as Malaysia, Indonesia, Pakistan, Thailand and India. Here we have used electron microscopy to study the three-dimensional structure of MrNV, revealing that the viral capsid - the protein shell that encloses the viral genome, protecting it and transporting it from one host to the next - is differently organised to capsids produced by other viruses in the nodavirus family. The virus was found to have large blade-like spikes on its outer surface that are likely important in the early stages of infection, when the virus attaches to and enters a host cell.

microbiology↗