Fuller, T. D. | bioRxiv Science

bioRxiv2021

An in vivo, neuron-specific approach for pairing translational and epigenetic signatures of early-life exercise

Aerobic exercise is well known to promote neuroplasticity and hippocampal memory. In the developing brain, early-life exercise (ELE) can lead to lasting improvements in hippocampal function, yet molecular mechanisms underlying this phenomenon have not been fully explored. In this study, adolescent transgenic mice harboring the "NuTRAP" (Nuclear tagging and Translating Ribosome Affinity Purification) cassette in Emx1 expressing neurons ("Emx1-NuTRAP" mice) undergo ELE followed by a hippocampal learning task, in order to determine the molecular underpinnings of exercise contributing to improved hippocampal memory performance. We simultaneously isolate and sequence translating mRNA and nuclear chromatin from a single hippocampus in a cell-type specific manner (excitatory neurons), demonstrate validity of our new technical approach, and couple multi-omics sequencing data to evaluate histone modifications H4K8ac and H3K27me3 and their influence on gene expression after ELE. We then evaluate new gene expression - histone modification relationships specifically during hippocampal memory consolidation that may play a critical role in facilitated memory after ELE. Our data reveal novel candidate gene-histone modification interactions and implicate gene regulatory pathways involved in ELEs impact on hippocampal learning and memory.

neuroscience↗

bioRxiv2021

Specific bacterial cell wall components influence the stability of Coxsackievirus B3

Enteric viruses infect the mammalian gastrointestinal tract and lead to significant morbidity and mortality worldwide. Data indicate that enteric viruses can utilize intestinal bacteria to promote viral replication and pathogenesis. However, the precise interactions between enteric viruses and bacteria are unknown. Here we examined the interaction between bacteria and Coxsackievirus B3, an enteric virus from the picornavirus family. We found that bacteria enhance the infectivity of Coxsackievirus B3 (CVB3) in vitro. Notably, specific bacteria are required as gram-negative Salmonella enterica, but not Escherichia coli, enhanced CVB3 infectivity and stability. Investigating the cell wall components of both S. enterica and E. coli revealed that structures in the O-antigen or core of lipopolysaccharide, a major component of the gram-negative bacterial cell wall, were required for S. enterica to enhance CVB3. To determine if these requirements were necessary for similar enteric viruses, we investigated if S. enterica and E. coli enhanced infectivity of poliovirus, another enteric virus in the picornavirus family. We found that, in contrast to CVB3, these bacteria enhanced the infectivity of poliovirus in vitro. Overall, these data indicate that distinct bacteria enhance CVB3 infectivity and stability, and specific enteric viruses may have differing requirements for their interactions with specific bacterial species. ImportancePrevious data indicate that several enteric viruses utilize bacteria to promote intestinal infection and viral stability. Here we show that specific bacteria and bacterial cell wall components are required to enhance infectivity and stability of Coxsackievirus B3 in vitro. These requirements are likely enteric virus-specific as the bacteria for CVB3 differs from poliovirus, a closely related virus. Therefore, these data indicate that specific bacteria and their cell wall components dictate the interaction with various enteric viruses in distinct mechanisms.

microbiology↗