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Ward, A. E.

Publications and source records attributed to Ward, A. E..

2 recordsLinked to original sources

Connecting Thiamine Availability to the Microbial Community Composition in Chinook Salmon Spawning Habitats of the Sacramento River Basin

Thiamine Deficiency Complex (TDC) is a major emerging threat to global populations of culturally and economically important populations of salmonids. Salmonid eggs and embryos can assimilate exogenous thiamine, and evidence suggests that microbial communities in benthic environments can produce substantial amounts of thiamine. We therefore hypothesize that microbially produced thiamine in both riverine surface water and hyporheic zones could serve to rescue early life stages of salmonids suffering from TDC. The distributions of thiamine and its metabolically related compounds (dTRCs) have never been determined in freshwater systems. Similarly, the microbial cycling of these compounds has never been investigated. Here we determine that all dTRCs are present in femto-picomolar concentrations across diverse salmon spawning habitats in Californias Sacramento River system. We observed that thiamine concentrations in the Sacramento River are orders of magnitude lower than marine environments, indicating substantial differences in thiamine cycling between these two environments. Our data suggest that the hyporheic zone is likely the source of thiamine to the overlying surface water. Temporal variations in dTRC concentration were observed where highest concentrations were seen when Chinook salmon were actively spawning. Significant correlations were identified between the richness of differentially abundant ASVs and dTRC concentrations. The influence of these ASVs on dTRC concentrations provide evidence of dTRC cycling by microbes in the hyporheic zone, which would influence the conditions where embryonic salmon incubate. Together, these results indicate a connection between microbial communities in freshwater habitats and the availability of thiamine to spawning TDC-impacted California Central Valley Chinook salmon.

microbiology↗

Serinc5 restricts HIV membrane fusion by altering lipid order and heterogeneity in the viral membrane

The host restriction factor, Serinc5, incorporates into budding HIV particles and inhibits their infection by an incompletely understood mechanism. We have previously reported that Serinc5 but not its paralogue, Serinc2, blocks HIV cell entry by membrane fusion, specifically by inhibiting fusion pore formation and dilation. A compelling body of work also suggests Serinc5 may alter the conformation and clustering of the HIV fusion protein, Env. To contribute an additional perspective to the developing model of Serinc5 restriction, we assessed Serinc2 and Serinc5s effects on HIV pseudoviral membranes. Using fluorescence lifetime imaging with an order sensitive dye, FLIPPER-TR, and by measuring pseudoviral membrane thickness via cryo electron microscopy (cryoEM), Serinc5 was found to increase membrane heterogeneity, skewing the distribution towards a larger fraction of the viral membrane in an ordered phase. We also directly observed for the first time the coexistence of membrane domains within individual viral membrane envelopes. Using a TIRF-based single particle fusion assay, we found that incorporation of exogenous phosphatidylethanolamine (PE) into the viral membrane rescued HIV pseudovirus fusion from restriction by Serinc5, which was accompanied by decreased membrane heterogeneity and order. This effect was specific for PE and did not depend on acyl chain length or saturation. Together, these data suggest that Serinc5 alters multiple interrelated properties of the viral membrane--lipid chain order, rigidity, line tension, and lateral pressure--which decrease accessibility of fusion intermediates and disfavor completion of fusion. These biophysical insights into Serinc5 restriction of HIV infectivity could contribute to the development of novel antivirals that exploit the same weaknesses of HIV and potentially other enveloped viruses.

biophysics↗