Biology subjects

Griswold, K. A.

Publications and source records attributed to Griswold, K. A..

4 recordsLinked to original sources

bioRxiv2026

Relatedness of Gardnerella prophages and their endolysins

The Gardnerella genus includes a complex sub-taxonomy of bacterial species and subgroups which have been implicated in bacterial vaginosis. We analyzed G. leopoldii, G. swidsinski, G. piotii, and G. vaginalis genomes available in public databases and predicted proviral sequences using Cenote-Taker3. We clustered 266 prophage sequences into 140 viral genera level groupings that encode four distinct gene clusters and 19 different lysin proteins. Analysis of the bacterial and prophage sequence phylogenies reveals that while there were no specific prophage sequence lineages that infected each bacterial host, there is clustering of the prophage sequences by bacterial species within the Gardnerella genus.

microbiology↗

bioRxiv2026

High-resolution spatial transcriptomics maps viral tropism and reveals spatially organized immune modules in viral encephalitis

Viral encephalitis is a debilitating disease that most commonly affects vulnerable populations, including the very young and elderly. Despite its severity, few countermeasures exist due to the structural and immunological complexities of the central nervous system (CNS). To better understand the spatial dynamics of viral spread and the concurrent host immune responses, we used high-resolution spatial transcriptomics to profile reovirus infection in the neonatal mouse brain at 3, 5, and 7 days post-infection. We constructed a comprehensive spatiotemporal atlas of infection, which revealed viral dissemination from sites of cerebrospinal fluid circulation to neighboring brain parenchyma, with enriched infection in the thalamus and midbrain coincident with Slc17a6 (VGLUT2) excitatory neurons. Unbiased spatial gene co-expression network analysis uncovered rich gene lists linked to temporal waves of host immune responses, originating with interferon-stimulated gene modules, followed by myeloid cell infiltration and adaptive cytotoxic T-cell responses at times of peak disease. Furthermore, we identified spatial correlation between viral transcripts and several upregulated host snoRNA-related genes (e.g., Nop58 and Snhg1) with high-confidence, suggesting viral use of host ribosomal modification machinery. We also observed a strong anti-correlation of astrocyte markers with reovirus transcripts, suggesting glial cell disruption. This work provides a high-definition spatial framework to understand interactions between viral infection and host immunity in the brain.

microbiology↗

bioRxiv2026

Gene regulatory networks define human airway epithelial cell types and their distinct responses to type I interferon

The human airway epithelium (HAE) is composed of diverse cell types that coordinate essential functions and host defenses. Among these defenses, interferons (IFNs) are central to antiviral programs. However, the gene regulatory networks (GRNs) governing HAE cellular identities and their IFN responses are incompletely defined. At single-cell resolution, we characterized the transcriptomes and accessible chromatin landscapes of HAE cell types, at steady state and following IFN{beta} stimulation. The resulting scRNA-seq and snATAC-seq data informed genome-scale GRN construction and inference of transcriptional circuits underlying cell identities. In response to IFN, we identified a shared transcriptional program across HAE cell types, and an expanded set of interferon-responsive genes exhibiting cell type-associated expression patterns. Cell type-associated transcription factors and chromatin accessibility contribute to distinct IFN-responsive gene expression programs. Together, these data provide a blueprint for molecular regulation of complex HAE responses and a foundation for therapeutic strategies to enhance host antiviral defense.

systems biology↗

bioRxiv2021

Chikungunya virus vaccine candidate incorporating synergistic mutations is attenuated and protects against virulent virus challenge

BackgroundChikungunya virus (CHIKV) is an arbovirus that periodically reemerges to cause large epidemics of arthritic disease. While the robust immunity elicited by live-attenuated virus (LAV) vaccine candidates makes them attractive, CHIKV vaccine development has been hampered by a high threshold for acceptable adverse events. MethodsWe evaluated the vaccine potential of a recently described LAV, SKE, that exhibits diminished replication in skeletal muscle cells due to insertion of target sequences for skeletal muscle-specific miR-206. We also evaluated whether these target sequences could augment safety of a LAV encoding a previously described attenuating mutation, E2 G82R, which on its own was too reactogenic in clinical trials. Attenuation of viruses containing these mutations was compared with a double mutant, SKE G82R. ResultsSKE was attenuated in both immunodeficient and immunocompetent mice and induced a robust neutralizing antibody response, indicating its vaccine potential. However, only SKE G82R elicited diminished swelling in immunocompetent mice at early time points post-inoculation, indicating that these mutations synergistically enhance safety of the vaccine candidate. ConclusionsThese data suggest that restriction of LAV replication in skeletal muscle enhances tolerability of reactogenic vaccine candidates and may improve the rational design of CHIKV vaccines.

microbiology↗