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Cull, S.

Publications and source records attributed to Cull, S..

2 recordsLinked to original sources

Swine influenza A virus infection dynamics and evolution in intensive pig production systems

Swine influenza A virus is one of the main viral pathogens responsible for respiratory disease in farmed pigs. Whilst outbreaks are often epidemic in nature, increasing reports suggest that continuous, endemic infection of herds is now common. The move towards larger herd sizes and increased intensification in the commercial pig industry may promote endemic infection, however, the impact that intensification has on swine influenza A virus infection dynamics and evolution is unclear. We carried out a longitudinal surveillance study over 18 months on two endemically infected, intensive pig farms. Frequent sampling of all production stages using individual and group sampling methods was performed, followed by virological and immunological testing and whole genome sequencing. We identified weaned pigs between 4-12 weeks old as the main reservoir of swine influenza A virus on the farms, with continuous, year-round infection. Despite the continuous nature of viral circulation, infection levels were not uniform, with increasing immunity at the herd level associated with reduced viral prevalence followed by subsequent rebound infection. A single virus subtype persisted on each farm for the entire duration of the study. Viral evolution was characterised by long periods of stasis punctuated by periods of rapid change coinciding with increasing immunity within the herd. An accumulation of mutations in the surface glycoproteins consistent with antigenic drift was observed, in addition to amino acid substitutions in the internal gene products as well as reassortment exchange of internal gene segments from newly introduced strains. These data demonstrate that long-term, continuous infection of herds with a single subtype is possible and document the evolutionary mechanisms utilised to achieve this. Author SummaryInfection with influenza A virus is widespread in pigs and contributes towards poor health and loss of productivity. Effective infection control measures are necessary to limit the impact of influenza on farms. However, modern farming practices are increasingly characterised by larger herd sizes and higher stocking densities. It is unclear how the move towards increased intensification impacts infectious diseases such as influenza. Accumulating evidence suggests that long-term infection of herds may be common. How influenza A virus can persist long-term is poorly understood. The aim of the current study was to monitor the infection status of pigs at each stage of the production process, measure the extent of the developing immune response and to characterise the evolutionary changes in the circulating influenza A viruses over time. Our findings provide insights into the dynamics of viral infection and evolution and may contribute to improved infection control strategies.

microbiology↗

The post-translational modification SUMO affects TDP-43 phase separation, compartmentalization, and aggregation in a zebrafish model

TDP-43 is a nuclear RNA-binding protein that can undergo liquid-liquid phase separation (LLPS) and forms pathological insoluble aggregates in frontotemporal dementia and amyotrophic lateral sclerosis (ALS). Perturbations of TDP-43 function are linked to mislocalization and neurodegeneration. By studying TDP-43 in vivo, we confirmed for the first time that TDP-43 undergoes LLPS and forms biomolecular condensates in spinal motor neurons (MNs). Importantly, we discovered that interfering with the K136 SUMOylation site of TDP-43 altered its phase separation behavior, reducing cytoplasmic mislocalization and aggregation. Introduction of the ALS-linked mutation G294V did not alter these LLPS characteristics, indicating that posttranslational modifications such as lysine-specific alterations can modulate TDP-43 pathogenesis through regulating phase separation. Altogether, our in vivo characterization of TDP-43 confirms the formation of dynamic nuclear TDP-43 condensates in zebrafish spinal neurons and establishes a critical platform to validate the molecular grammar of phase separation that underpins TDP-43 aggregation in ALS and other proteinopathies.

molecular biology↗