Biology subjects

Behboudi, S.

Publications and source records attributed to Behboudi, S..

3 recordsLinked to original sources

bioRxiv2025

A major histocompatibility complex (MHC) class II molecule that binds the same viral pathogen peptide with both nonamer and decamer core sequences for presentation to T cells

Classical molecules encoded by the major histocompatibility complex (MHC) are central to immune responses. Compared to typical mammals, the chicken MHC is small and simple, determining life or death from economically-important pathogens like avian influenza virus and Mareks disease virus (MDV). Several genes within the tightly-linked chicken MHC have been suggested to determine resistance and susceptibility to MDV, but it was a surprise to find that the dominantly-expressed class II molecule from the resistant B2 haplotype employed a novel peptide-binding mode with a decamer core sequence compared to the susceptible B19 haplotype with a typical nonamer core. We examined the crystal structure of the dominantly-expressed class II molecule from another resistant haplotype, B21, which is extremely frequent in commercial chicken flocks, to find that it bound the same MDV peptide with both nonamer and decamer cores, revealing an unexpected plasticity of binding that potentially increases the immune response to this devastating pathogen.

immunology↗

bioRxiv2025

High-risk clonal groups of Avian Pathogenic Escherichia coli (APEC) demonstrate heterogeneous phenotypic characteristics in vitro and in vivo

Avian Pathogenic Escherichia coli (APEC), a major bacterial pathogen of poultry, is comprised of a diverse range of high-risk clonal groups. However, phenotypic interactions with the avian host cell and how they may differ between lineages remains poorly understood. Therefore, the ability of predominant and outbreak-associated APEC clonal groups to invade and survive within avian host cells, as well as virulence within the Galleria mellonella infection model was investigated. The molecular characterisation of APEC isolated from an outbreak of colibacillosis in turkey poults in the UK, identified APEC sequence type (ST)-101 as the dominant clonal group, carrying a high number of virulence factors. As such, ST-101 was compared as an outbreak-associated lineage to a range of predominant APEC high-risk clonal groups (ST-23, ST-140, ST-95, ST-117). Utilising in vitro cell culture models, APEC isolates displayed comparable adhesion to 8E11 chicken epithelial gut and HD11 chicken macrophage cell lines. However, a trend of increased invasion of the 8E11 cells, and intracellular survival within HD11 macrophages was observed for ST-95, ST-101, and ST-140 APEC, relative to ST-23 and ST-117, suggestive of pronounced phenotypic differences between clonal groups. However, in HD11 cell assays, no difference in magnitude of elicited immune response was observed between lineages, indicating lineages had differing capacities to resist phagocyte killing. In vivo virulence in the Galleria mellonella infection model was also observed to differ between APEC genotypes, with ST-117 inducing the highest mortality, despite the comparatively lower epithelial invasion and intramacrophage survival to other lineages. Collectively, this suggests a distinct phenotypic profile associated with high-risk clonal groups within APEC, potentially allowing the future development of broad-spectrum disease management strategies.

microbiology↗

bioRxiv2018

Targeted induction of de novo Fatty acid synthesis enhances MDV replication in a COX-2/PGE2 dependent mechanism through EP2 and EP4 receptors engagement

Many viruses alter de novo Fatty Acid (FA) synthesis pathway, which can increase availability of energy for replication and provide specific cellular substrates for particle assembly. Mareks disease virus (MDV) is a herpesvirus that causes deadly lymphoma and has been linked to alterations of lipid metabolism in MDV-infected chickens. However, the role of lipid metabolism in MDV replication is largely unknown. We demonstrate here that infection of primary chicken embryonic fibroblast with MDV activates de novo lipogenesis, which is required for virus replication. In contrast, activation of Fatty Acid Oxidation (FAO) reduced MDV titer, while inhibition of FAO moderately increased virus replication. Thus optimized virus replication occurs if synthetized fatty acids are not used for generation of energy in the infected cells, and they are likely converted to lipid compounds, which are important for virus replication. We showed that infection with MDV activates COX-2/PGE2 pathway and increases the biosynthesis of PGE2, a lipid mediator generated from arachidonic acid. Inhibition of COX-2 or PGE2 receptors, namely EP2 and EP4 receptors, reduced MDV titer, indicating that COX-2/PGE2 pathway are involved in virus replication. Our data show that the FA synthesis pathway inhibitors reduce COX-2 expression level and PGE2 synthesis in MDV infected cells, arguing that there is a direct link between virus-induced fatty acid synthesis and activation of COX-2/PGE2 pathway. This notion was confirmed by the results showing that PGE2 can restore MDV replication in the presence of the FA synthesis pathway inhibitors. Taken together, our data demonstrate that MDV uses FA synthesis pathway to enhance PGE2 synthesis and promote MDV replication through EP2 and EP4 receptors engagement.

microbiology↗