Biology subjects

Wallace, M. A.

Publications and source records attributed to Wallace, M. A..

4 recordsLinked to original sources

bioRxiv2024

Positive correlations in susceptibility to a diverse panel of viruses across host species

Our ability to predict the emergence of novel viruses relies on there being generalisable patterns in the susceptibilities of hosts to novel infections. Studies investigating variation in susceptibility among host species have consistently shown that closely related hosts share similar susceptibilities to a given virus. However, the extent to which such phylogenetic patterns of susceptibility are correlated amongst diverse sets of viruses is unclear. Here, we investigate phylogenetic correlations in susceptibility among Drosophilidae hosts to a panel of eleven different invertebrate viruses, comprising seven unique virus species, six unique families, and both RNA and DNA viruses. The susceptibility of hosts to each pair of viruses tested was either positively correlated across host species or did not show evidence of correlation. No negative correlations, indicative of evolutionary trade-offs in host susceptibility to different viruses, were detected between any virus pairs. The strength of correlations were generally higher in viruses of the same species and family, consistent with virus phylogenetic patterns in host infectivity. Our results suggest that generalised host susceptibility can result in positive correlations, even between highly diverged viruses, while specialised interactions with individual viruses cause a stepwise decrease in correlation strength between viruses from the within-species, to the within-family, to the across-family level.

evolutionary biology↗

bioRxiv2023

Secretory Leukocyte Protease Inhibitor Protects Against Severe Urinary Tract Infection in Mice

Millions suffer from urinary tract infections (UTIs) worldwide every year with women accounting for the majority of cases. Uropathogenic Escherichia coli (UPEC) causes most of these primary infections and leads to 25% becoming recurrent or chronic. To repel invading pathogens, the urinary tract mounts a vigorous innate immune response that includes the secretion of antimicrobial peptides (AMPs), rapid recruitment of phagocytes and exfoliation of superficial umbrella cells. Here, we investigate secretory leukocyte protease inhibitor (SLPI), an AMP with antiprotease, antimicrobial and immunomodulatory functions, known to play protective roles at other mucosal sites, but not well characterized in UTIs. Using a mouse model of UPEC-caused UTI, we show that urine SLPI increases in infected mice and that SLPI is localized to bladder epithelial cells. UPEC infected SLPI-deficient (Slpi-/-) mice suffer from higher urine bacterial burdens, prolonged bladder inflammation, and elevated urine neutrophil elastase (NE) levels compared to wild-type (Slpi+/+) controls. Combined with bulk bladder RNA sequencing, our data indicate that Slpi-/- mice have a dysregulated immune and tissue repair response following UTI. We also measure SLPI in urine samples from a small group of female subjects 18-49 years old and find that SLPI tends to be higher in the presence of a uropathogen, except in patients with history of recent or recurrent UTI (rUTI), suggesting a dysregulation of SLPI expression in these women. Taken together, our findings show SLPI protects against acute UTI in mice and provides preliminary evidence that SLPI is likewise regulated in response to uropathogen exposure in women.

immunology↗

bioRxiv2023

Naturally occurring viruses of Drosophila reduce offspring number and lifespan

Drosophila remains a pre-eminent insect model system for host-virus interaction, but the host range and fitness consequences of the drosophilid virome are poorly understood. Metagenomic studies have reported over 160 viruses associated with Drosophilidae, but few isolates are available to characterise the Drosophila immune response, and most characterisation has relied on injection and systemic infection. Here we use a more natural infection route to characterise the fitness effects of infection and to study a wider range of viruses. We exposed laboratory D. melanogaster to 23 naturally occurring viruses from wild-collected drosophilids. We recorded transmission rates along with two components of female fitness: survival and the lifetime number of adult offspring produced. Nine different viruses transmitted during contact with laboratory D. melanogaster, although for the majority, rates of transmission were less than 20%. Five virus infections led to a significant decrease in lifespan (D. melanogaster nora virus, D. immigrans nora virus, Muthill virus, galbut virus and Prestney Burn virus), and three led to a reduction in the total number of offspring. Our findings demonstrate the utility of the Drosophila model for community-level studies of host-virus interactions, and suggest that viral infection could be a substantial fitness burden on wild flies.

evolutionary biology↗

bioRxiv2020

The discovery, distribution and diversity of DNA viruses associated with Drosophila melanogaster in Europe

Drosophila melanogaster is an important model for antiviral immunity in arthropods, but very few DNA viruses have been described from the family Drosophilidae. This deficiency limits our opportunity to use natural host-pathogen combinations in experimental studies, and may bias our understanding of the Drosophila virome. Here we report fourteen DNA viruses detected in a metagenomic analysis of approximately 6500 pool-sequenced Drosophila, sampled from 47 European locations between 2014 and 2016. These include three new Nudiviruses, a new and divergent Entomopox virus, a virus related to Leptopilina boulardi filamentous virus, and a virus related to Musca domestica salivary gland hypertrophy virus. We also find an endogenous genomic copy of Galbut virus, a dsRNA Partitivirus, segregating at very low frequency. Remarkably, we find that Drosophila Vesanto virus, a small DNA virus previously described as a Bidnavirus, may be composed of up to 12 segments and represent a new lineage of segmented DNA viruses. Two of the DNA viruses, Drosophila Kallithea nudivirus and Drosophila Vesanto virus are relatively common, found in 2% or more of wild flies. The others are rare, with many likely to be represented by a single infected fly. We find that virus prevalence in Europe reflects the prevalence seen in publicly-available datasets, with Drosophila Kallithea nudivirus and Drosophila Vesanto virus the only ones commonly detectable in public data from wild-caught flies and large population cages, and the other viruses being rare or absent. These analyses suggest that DNA viruses are at lower prevalence than RNA viruses in D. melanogaster, and may be less likely to persist in laboratory cultures. Our findings go some way to redressing an earlier bias toward RNA virus studies in Drosophila, and lay the foundation needed to harness the power of Drosophila as a model system for the study of DNA viruses.

microbiology↗