Biology subjects

Ballif, B. A.

Publications and source records attributed to Ballif, B. A..

3 recordsLinked to original sources

bioRxiv2024

Variant mutation in SARS-CoV-2 nucleocapsid enhances viral infection via altered genomic encapsidation

The evolution of SARS-CoV-2 variants and their respective phenotypes represents an important set of tools to understand basic coronavirus biology as well as the public health implications of individual mutations in variants of concern. While mutations outside of Spike are not well studied, the entire viral genome is undergoing evolutionary selection, particularly the central disordered linker region of the nucleocapsid (N) protein. Here, we identify a mutation (G215C), characteristic of the Delta variant, that introduces a novel cysteine into this linker domain, which results in the formation of a disulfide bond and a stable N-N dimer. Using reverse genetics, we determined that this cysteine residue is necessary and sufficient for stable dimer formation in a WA1 SARS-CoV-2 background, where it results in significantly increased viral growth both in vitro and in vivo. Finally, we demonstrate that the N:G215C virus packages more nucleocapsid per virion and that individual virions are larger, with elongated morphologies.

microbiology↗

bioRxiv2021

A global map of the Zika virus phosphoproteome reveals host-driven regulation of viral budding

Flaviviruses are enveloped, positive-strand RNA viruses that cause millions of infections in the human population annually. Although Zika virus (ZIKV) had been detected in humans as early as the 1950s, its reemergence in South America in 2015 resulted in a global health crisis. While flaviviruses encode 10 proteins that can be post-translationally modified by host enzymes, little is known regarding post-translational modifications (PTMs) of the flavivirus proteome. We used mass spectrometry to comprehensively identify host-driven PTMs on the ZIKV proteome. This approach allowed us to identify 43 PTMs across 8 ZIKV proteins, including several that are highly conserved within the Flavivirus genus. Notably, we found two phosphosites on the ZIKV envelope protein that are functionally important for viral propagation. Both appear to regulate viral budding, while one also impacts ZIKV cytopathogenicity. Additionally, we discovered host kinases that interact with ZIKV proteins and determined that Bosutinib--an FDA-approved tyrosine kinase inhibitor that targets some of these host kinases--impairs ZIKV growth, in part by blocking phosphorylation of a tyrosine residue on the envelope protein. Thus, we have defined a high-resolution map of host-driven PTMs on ZIKV proteins as well as cellular interacting kinases, uncovered novel mechanisms of host driven-regulation of ZIKV budding and cytopathogenicity, and identified an FDA-approved inhibitor of ZIKV growth.

microbiology↗

bioRxiv2020

Clockwise and counterclockwise hysteresis characterize state changes in the same aquatic ecosystem

Incremental increases in a driver variable, such as nutrients or detritus, can trigger abrupt shifts in aquatic ecosys-tems. Once these ecosystems change state, a simple reduction in the driver variable may not return them to their original state. Because of the long time scales involved, we still have a poor understanding of the dynamics of ecosys-tem recovery after a state change. A model system for understanding ecosystem recovery is the aquatic microecosystem that inhabits the cup-shaped leaves of the pitcher plant Sarracenia purpurea. With enrichment of organic matter, this system flips within 1 to 3 days from an oxygen-rich state to an oxygen-poor (hypoxic) state. In a replicated green-house experiment, we enriched pitcher plant leaves at different rates with bovine serum albumin (BSA), a molecular substitute for detritus. Changes in dissolved oxygen ([O2]) and undigested BSA concentration were monitored during enrichment and recovery phases. At low enrichment rates, ecosystems showed a substantial lag in the recovery of [O2] (clockwise hysteresis). At intermediate enrichment rates, [O2] tracked the levels of undigested BSA with the same profile during the enrichment and recovery phases (no hysteresis). At high enrichment rates, we observed a novel response: changes in [O2] were proportionally larger during the recovery phase than during the enrichment phase (counter-clockwise hysteresis). These experiments demonstrate that detrital enrichment rate can modulate a diversity of hysteretic responses in a single aquatic ecosystem. With counter-clockwise hysteresis, rapid reduction of a driver variable following high enrichment rates may be a viable restoration strategy.

ecology↗