Paul Digard

ORCID: 0000-0002-0872-9440
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About
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Research Areas
  • Influenza Virus Research Studies
  • interferon and immune responses
  • RNA and protein synthesis mechanisms
  • Respiratory viral infections research
  • Viral gastroenteritis research and epidemiology
  • Virus-based gene therapy research
  • Animal Disease Management and Epidemiology
  • Animal Virus Infections Studies
  • Herpesvirus Infections and Treatments
  • Infection Control and Ventilation
  • Viral Infections and Vectors
  • Viral Infections and Immunology Research
  • RNA modifications and cancer
  • Bacteriophages and microbial interactions
  • SARS-CoV-2 and COVID-19 Research
  • Cytomegalovirus and herpesvirus research
  • RNA Research and Splicing
  • Immune Response and Inflammation
  • COVID-19 and healthcare impacts
  • Autophagy in Disease and Therapy
  • Plant Virus Research Studies
  • Mosquito-borne diseases and control
  • Lipid Membrane Structure and Behavior
  • Cellular transport and secretion
  • Monoclonal and Polyclonal Antibodies Research

Roslin Institute
2016-2025

University of Edinburgh
2016-2025

State Forestry and Grassland Administration
2023

University of Chinese Academy of Sciences
2023

Shanxi Agricultural University
2023

Taishan Medical University
2023

Shandong First Medical University
2023

Wuhan Institute of Virology
2023

Hohhot First Hospital
2023

Chinese Academy of Sciences
2023

Influenza's Cryptic Constraint Because of the well-known pandemic potential influenza viruses, it is important to understand range molecular interactions between virus and its host. Despite years intensive research on virus, Jagger et al. (p. 199 , published online 28 June; see Perspective by Yewdell Ince ) have found that A has been hiding a gene in small negative-sense RNA genome. An overlapping open reading frame was contained PA viral polymerase gene, which accessed ribosomal...

10.1126/science.1222213 article EN Science 2012-06-29

All viruses with negative-sense RNA genomes encode a single-strand RNA-binding nucleoprotein (NP). The primary function of NP is to encapsidate the virus genome for purposes transcription, replication and packaging. purpose this review illustrate using influenza as well-studied example that molecule much more than structural protein, but also functions key adapter between host cell processes. It does so through ability interact wide variety viral cellular macromolecules, including RNA,...

10.1099/0022-1317-83-4-723 article EN Journal of General Virology 2002-04-01

ABSTRACT Influenza A virus segment 2 is known to encode two polypeptides in overlapping open reading frames: PB1, the polymerase, and PB1-F2, a proapoptotic virulence factor. We show that third major polypeptide synthesized from PB1 mRNA via differential AUG codon usage. 40 directs translation of an N-terminally truncated version (N40) lacks transcriptase function but nevertheless interacts with PB2 polymerase complex cellular environment. Importantly, expression N40, are interdependent,...

10.1128/jvi.00826-09 article EN Journal of Virology 2009-06-04

Autophagy recycles cellular components and defends cells against intracellular pathogens. While viruses must evade autophagocytic destruction, some can also subvert autophagy for their own benefit. The ability of influenza A virus (IAV) to depends on the Matrix 2 (M2) ion-channel protein. We show that cytoplasmic tail IAV M2 interacts directly with essential protein LC3 promotes relocalization unexpected destination plasma membrane. binding is mediated by a highly conserved LC3-interacting...

10.1016/j.chom.2014.01.006 article EN cc-by Cell Host & Microbe 2014-02-01

Segment 7 of influenza A virus produces up to four mRNAs. Unspliced transcripts encode M1, spliced mRNA2 encodes the M2 ion channel, while protein products from mRNAs 3 and 4 have not previously been identified. The plays important roles in entry assembly, is a target for antiviral drugs vaccination. Surprisingly, essential replication laboratory setting, although its loss attenuates virus. To better understand how IAV might replicate without M2, we studied reversion mechanism an M2-null...

10.1371/journal.ppat.1002998 article EN cc-by PLoS Pathogens 2012-11-01

In early 2024, an unprecedented outbreak of H5N1 high pathogenicity avian influenza was detected in dairy cattle the USA. The epidemic remains uncontrolled, with spillbacks into poultry, wild birds and other mammals including humans. Here, we present molecular virological evidence that B3.13 genotype viruses rapidly accumulated adaptations polymerase genes enabled better replication bovine cells, as well cells mammalian species humans pigs. We find several gained evolution these PB2 M631L,...

10.1101/2025.01.06.631435 preprint EN cc-by bioRxiv (Cold Spring Harbor Laboratory) 2025-01-06

Influenza virus transcription occurs in the nuclei of infected cells, where viral genomic RNAs are complexed with a nucleoprotein (NP) to form ribonucleoprotein (RNP) structures. Prior assembly into progeny virions, these RNPs exit nucleus and accumulate cytoplasm. The mechanisms responsible for RNP export only partially understood but have been proposed involve M1 NS2 polypeptides. We found that drug leptomycin B (LMB), which specifically inactivates cellular CRM1 polypeptide, caused...

10.1128/jvi.75.1.408-419.2001 article EN Journal of Virology 2001-01-01

ABSTRACT The viral RNA (vRNA) genome of influenza A virus is replicated in the nucleus, exported to cytoplasm as ribonucleoproteins (RNPs), and trafficked plasma membrane through uncertain means. Using fluorescent situ hybridization detect vRNA well live cell imaging fluorescently labeled RNPs, we show that an early event cytoplasmic trafficking involves accumulation near microtubule organizing center multiple types strains. Here, RNPs colocalized with Rab11, a pericentriolar recycling...

10.1128/jvi.02606-10 article EN Journal of Virology 2011-02-10

A key question in pandemic influenza is the relative roles of innate immunity and target cell depletion limiting primary infection modulating pathology. Here, we model these interactions using detailed data from equine virus infection, combining viral immune (type I interferon) kinetics with estimates depletion. The resulting dynamics indicate a powerful role for controlling rapid peak shedding. As corollary, cells are much less depleted than suggested by human based only on virus-shedding...

10.1128/jvi.02078-09 article EN Journal of Virology 2010-02-04

ABSTRACT Influenza A virus buds through the apical plasma membrane, forming enveloped particles that can take shape of pleomorphic spheres or vastly elongated filaments. For either type virion, factors responsible for separation viral and cell membranes are not known. We find cellular Rab11 (a small GTP-binding protein involved in endocytic recycling) Rab11-family interacting 3 ([FIP3] which plays a role membrane trafficking regulation actin dynamics) both required to support formation...

10.1128/jvi.00307-10 article EN Journal of Virology 2010-04-01

Four monoclonal antibodies to glycoprotein D (gD) of herpes simplex virus (HSV) types 1 and 2 neutralized in the presence complement but exhibited diverse activities its absence. Amino acid substitutions that conferred resistance neutralization by each antibody were identified deriving nucleotide sequence gD gene from resistant mutants. Each selected a substitution different parts molecule mutants single always arose same mutation. One reacted with synthetic oligopeptide corresponding region...

10.1099/0022-1317-67-6-1001 article EN Journal of General Virology 1986-06-01

Genome segmentation facilitates reassortment and rapid evolution of influenza A virus. However, complicates particle assembly as virions must contain all eight vRNA species to be infectious. Specific packaging signals exist that extend into the coding regions most if not segments, but these RNA motifs are poorly defined. We measured codon variability in a large dataset sequences identify areas low nucleotide sequence variation independent amino acid conservation each segment. Most clusters...

10.1093/nar/gkm087 article EN cc-by-nc Nucleic Acids Research 2007-03-01

The matrix (M1) protein of influenza A virus is a multifunctional that plays essential structural and functional roles in the life cycle. It drives budding major component virion, where it forms an intermediate layer between viral envelope integral membrane proteins genomic ribonucleoproteins (RNPs). also helps to control intracellular trafficking RNPs. These are mediated primarily via protein-protein interactions with possibly cellular proteins. Here, regions M1 involved binding RNPs...

10.1099/vir.0.82809-0 article EN cc-by Journal of General Virology 2007-07-10

ABSTRACT The genomic viral RNA (vRNA) segments of influenza A virus contain specific packaging signals at their termini that overlap the coding regions. To further characterize cis -acting in segment 7, we introduced synonymous mutations into terminal Mutation codons are normally highly conserved reduced growth embryonated eggs and MDCK cells between 10- 1,000-fold compared to wild-type virus, whereas similar alterations nonconserved had little effect. In all cases, growth-impaired viruses...

10.1128/jvi.01634-08 article EN Journal of Virology 2008-09-25

Professional phagocytosis in mammals is considered to be performed exclusively by myeloid cell types. In this study, we demonstrate, for the first time, that a mammalian lymphocyte subset can operate as professional phagocyte. By using confocal microscopy, transmission electron and functional Ag presentation assays, find freshly isolated human peripheral blood gammadelta T cells phagocytose Escherichia coli 1 microm synthetic beads via Ab opsonization CD16 (FcgammaRIII), leading processing...

10.4049/jimmunol.0901772 article EN The Journal of Immunology 2009-10-20

Influenza viruses are the cause of yearly epidemics and occasional pandemics that represent a significant challenge to public health. Current control strategies imperfect there is an unmet need for new antiviral therapies. Here, we report identification small molecule compounds able effectively specifically inhibit growth influenza A B in cultured cells through targeting assembly interface viral RNA-dependent RNA polymerase. Using existing crystal structure primary protein–protein between...

10.1073/pnas.1119817109 article EN Proceedings of the National Academy of Sciences 2012-04-02

ABSTRACT PA-X is a fusion protein of influenza A virus encoded in part from +1 frameshifted X open reading frame (X-ORF) segment 3. We show that the X-ORFs diverse viruses can be divided into two groups differ selection pressure and likely function, reflected presence an internal stop codon change synonymous diversity. Notably, truncated forms evolved convergently swine dogs, suggesting strong species-specific effect.

10.1128/jvi.01677-12 article EN Journal of Virology 2012-09-06

Chickens are susceptible to infection with a limited number of Influenza A viruses and potential source human influenza pandemic. In particular, H5 H7 haemagglutinin subtypes can evolve from low highly pathogenic strains in gallinaceous poultry. Ducks on the other hand natural reservoir for these able withstand most avian strains. Transcriptomic sequencing lung ileum tissue samples birds infected high (H5N1) (H5N2) has allowed us compare early host response infections both species. (but not...

10.1186/s12864-015-1778-8 article EN cc-by BMC Genomics 2015-08-03

Previously, we demonstrated that frequencies of CpG and UpA dinucleotides profoundly influence the replication ability echovirus 7 (Tulloch et al., 2014). Here, show influenza A virus (IAV) with maximised these in segment 5 showed comparable attenuation cell culture compared to unmodified a permuted control (CDLR). Attenuation was also manifested vivo, 10-100 fold reduced viral loads lungs mice infected 200PFU CpG-high UpA-high mutants. However, both induced powerful inflammatory cytokine...

10.7554/elife.12735 article EN cc-by eLife 2016-02-16
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