Biology subjects

Cherry, S. R.

Publications and source records attributed to Cherry, S. R..

4 recordsLinked to original sources

bioRxiv2026

Jamestown Canyon virus rapidly adapts to mosquito cells through multiple M segment mutations

Jamestown Canyon virus (JCV) is a mosquito-borne orthobunyavirus with an unusually broad host and vector range. Despite increasing mosquito-to-human spillover, the viral determinants governing host adaptation remain poorly defined. We examined changes in JCV replication during serial passage in mosquito cells and sought to link adaptive changes in viral fitness to specific genetic mutations. In mosquito-derived C6/36 cells, JCV exhibited a distinct "lag-burst" phenotype in which viral replication remained nearly undetectable for 10 days before abruptly increasing. Strikingly, following reinfection of fresh C6/36 cells, JCV that had been passaged once in mosquito cells exhibited immediate, robust replication with no detectable lag phase. Sequencing before and after passage identified multiple M segment mutations associated with enhanced replication. Using a plasmid-based reverse genetics system, individual mutations were introduced into recombinant JCV and evaluated for their effects on replication in mosquito cells. All tested mutations independently enhanced replication efficiency, demonstrating that adaptation can arise through multiple independent genetic pathways. However, no individual mutation fully reproduced the phenotype acquired naturally through mosquito cell passage. Together, these findings demonstrate that JCV rapidly adapts to mosquito cells under minimal selective pressure and highlight the potential for emergence of increasingly well-adapted viral variants.

microbiology↗

bioRxiv2025

Alternate isoforms of IRF7 Differentially Regulate Interferon Expression to Tune Response to Viral Infection

Interferon Regulatory Factor 7 (IRF7), and its homologue IRF3, are master transcriptional regulators of the innate immune response. IRF7 binds to promoters of interferon {beta} (IFN{beta}) and several IFNs as a homodimer or as a heterodimer with IRF3 to drive expression of these type I IFNs, which in turn activate downstream signaling pathways to promote expression of antiviral genes. Here we demonstrate that alternative splicing of the first intron within the coding region of IRF7 is highly regulated across immune tissues and in response to immunologic signals including viral infection. Retention of this intron generates an alternative translation start site, resulting in a N-terminally extended form of the protein (exIRF7) with distinct function from the canonical version of IRF7 (cIRF7). We find that exIRF7 uniquely activates a gene expression program, including IFN{beta}, in response to innate immune triggers. Mechanistically, this enhanced activity of exIRF7 relative to cIRF7 is through increased homodimerization and association with IRF3 on DNA. Furthermore, the enhanced transcriptional activity of exIRF7 controls viral infection to a greater extent than cIRF7, demonstrating that alternative splicing of IRF7 is a previously unrecognized mechanism used by cells to tune the interferon response to control viral infections and other immune challenges. HighlightsO_LIIntron retention in the human IRF7 gene generates a distinct protein isoform that differs in the N-terminus. C_LIO_LIIRF7 intron retention is regulated in a stimuli- and cell-type specific manner. C_LIO_LIThe extended version of IRF7, produced by intron retention, exhibits enhanced transcriptional activation of type I interferon genes. C_LIO_LICells expressing the extended version of IRF7 are more resistant to viral infection. C_LI

molecular biology↗

bioRxiv2025

Effect of obesity on the acute response to SARS-CoV-2 infection and development of post-acute sequelae of COVID-19 (PASC) in nonhuman primates

Long-term adverse consequences of SARS-CoV-2 infection, termed "long COVID" or post-acute sequelae of COVID (PASC), are a major component of overall COVID-19 disease burden. Prior obesity and metabolic disease increase the severity of acute disease, but SARS-CoV-2 infection also contributes to the development of new-onset metabolic disease. Since the COVID pandemic occurred in the context of the global obesity epidemic, an important question is the extent to which pre-existing obesity modifies long-term responses to SARS-CoV-2 infection. We utilized a nonhuman primate model to compare the effects of infection with the SARS-CoV-2 delta variant in lean and obese/insulin-resistant adult male rhesus macaques over a 6-month time course. While some longitudinal responses to SARS-CoV-2 infection, including overall viral dynamics, SARS-CoV-2-specific IgG induction, cytokine profiles, and tissue persistence of viral RNA, did not appreciably differ between lean and obese animals, other responses, including neutralizing Ab dynamics, lung pathology, body weight, degree of insulin sensitivity, adipocytokine profiles, body temperature, and nighttime activity levels were significantly different in lean versus obese animals. Furthermore, several parameters in lean animals were altered following SARS-CoV-2 infection to resemble those in obese animals. Notably, persistent changes in multiple parameters were present in most animals, suggesting that PASC may be more prevalent than estimated from self-reported symptoms in human studies.

pathology↗

bioRxiv2018

Real-time whole-plant dynamics of heavy metal transport in Arabidopsis halleri and Arabidopsis thaliana by gamma-ray imaging

Heavy metals such as zinc are essential for plant growth, but toxic at high concentrations. Despite our knowledge of the molecular mechanisms of heavy metal uptake by plants, experimentally addressing the real-time whole-plant dynamics of heavy metal uptake and partitioning has remained a challenge. To overcome this, we applied a high sensitivity gamma-ray imaging system to image uptake and transport of radioactive 65Zn in whole-plant assays of Arabidopsis thaliana and the Zn hyperaccumulator A. halleri. We show that our system can be used to quantitatively image and measure uptake and root-to-shoot translocation dynamics of zinc in real time. In the metal hyperaccumulator Arabidopsis halleri, 65Zn uptake and transport from its growth media to the shoot occurs rapidly and on time scales similar to those reported in rice. In transgenic A. halleri plants in which expression of the zinc transporter gene HMA4 is suppressed by RNAi, 65Zn uptake is completely abolished.\n\nHIGHLIGHTWe have used gamma-ray imaging to visualize the stark differences of real-time whole-plant dynamics of zinc root-to-shoot transport in heavy metal hyperaccumulating and non-accumulating Arabidopsis.

plant biology↗