Biology subjects

Carmody, A. B.

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

4 recordsLinked to original sources

bioRxiv2026

Epigenetic regulation of DPP4 receptor expression by NONO enables replication of MERS-CoV

Middle East respiratory syndrome coronavirus (MERS-CoV), first reported in 2012, belongs to the Betacoronavirus genus, including SARS-CoV and SARS-CoV-2. Human-to-human transmission of MERS-CoV appears inefficient, but repeated spillover events have been reported from at least 27 countries, raising concern for future emergent events. Coronaviruses (CoVs) rely extensively on host proteins to support their replication. Several studies have implicated the paraspeckle non-POU domain-containing octamer-binding protein (NONO) as an RNA-binding protein (RBP) that binds to CoV genomes, but the role of this protein in regulating replication is unknown. Here, we show that NONO is required for expression of dipeptidyl peptidase 4 (DPP4, also known as CD26), the major cellular receptor required for MERS-CoV attachment and entry. NONO did not impact DPP4 mRNA processing or stability but instead promoted DPP4 transcription through control of active H3K4me3 and repressive H3K27me3 histone modifications at the DPP4 locus. Together, these findings identify NONO as a key proviral host factor for MERS-CoV and reveal an epigenetic mechanism linking a host RBP to viral entry receptor expression that may represent a target for therapeutic strategies.

microbiology↗

bioRxiv2025

Dissection of amino acid acquisition pathways in Borrelia burgdorferi uncovers unique physiological responses

Borrelia burgdorferi, the causative agent of Lyme disease, is well known for its unique morphology, physiology, and enzootic lifecycle. Building on previous work that showed peptide transport is essential for viability, we endeavored to more clearly define the impact of peptide starvation on the spirochete and directly compare peptide starvation to targeted free amino acid starvation. Herein, we confirm the ability of a putative GltP, BB0401, to facilitate transport of glutamate and aspartate as well as demonstrate its requirement for cell growth and motility. Using conditional mutants for both peptide transport and BB0401, we characterize these systems throughout the enzootic cycle, both confirming their essential role during murine infection and revealing that they are, surprisingly, dispensable during prolonged colonization of the tick midgut. We broadly define the metabolic perturbations resulting from these amino acid starvation models and show that, even under the most severe amino acid stress, B. burgdorferi is unable to modulate its physiological response via the canonical (p)ppGpp-driven stringent response.

microbiology↗

bioRxiv2024

Jamaican fruit bats (Artibeus jamaicensis) competence for Ebola virus but not Marburg virus is driven by intrinsic differences in viral entry and IFN-I signaling antagonism.

Ebola virus (EBOV) and Marburg virus (MARV) are zoonotic filoviruses that cause hemorrhagic fever in humans. Bat species in both Chiropteran suborders host filoviruses, suggesting that bats may have coevolved with this viral family. Correlative data implicate bats as natural EBOV hosts, but neither a full-length genome nor an EBOV isolate has been found in any bats sampled. Here, we modelled filovirus infection in the Jamaican fruit bat (JFB), Artibeus jamaicensis. Bats were inoculated with either EBOV or MARV through a combination of oral, intranasal, and subcutaneous routes. EBOV-infected bats supported systemic virus replication and shed infectious virus orally. In contrast, MARV replicated only transiently and was not shed. In vitro, JFB cells replicate EBOV more efficiently than MARV, and MARV infection induced innate antiviral responses that EBOV efficiently suppressed. Experiments using VSV pseudoparticles or replicating VSV expressing the EBOV or MARV glycoprotein demonstrated an advantage for EBOV entry and replication early, respectively, in JFB cells. Overall, this study describes filovirus species-specific phenotypes for both JFB and their cells.

immunology↗

bioRxiv2022

Chlamydia trachomatis effectors target the mitochondria and alter mitochondrial protein composition

Mitochondria are critical cellular organelles that perform a wide variety of functions including energy production and immune regulation. To perform these functions, mitochondria contain approximately 1,500 proteins, the majority of which are encoded in the nuclear genome, translated in the cytoplasm, and translocated to the mitochondria using distinct mitochondria targeting sequences (MTS). Bacterial proteins can also contain MTS and localize to the mitochondria. For the obligate intracellular human pathogen, Chlamydia trachomatis, interaction with various host cell organelles promotes intracellular replication. However, the extent and mechanisms through which Chlamydia interact directly with mitochondria remain unclear. We investigated the presence of MTS in the C. trachomatis genome and discovered 30 genes with around 70% or greater probability of mitochondrial localization. Five are translocated to the mitochondria upon ectopic expression in HeLa cells. Mass spectrometry of isolated mitochondria from infected cells revealed that two of these proteins localize to the mitochondria during infection. Comparison of mitochondria from infected and uninfected cells suggests that chlamydial infection affects mitochondrial protein composition. Around 125 host proteins were significantly decreased or absent in mitochondria from infected cells. Among these are pro-apoptotic factors and those related to mitochondrial fission/fusion dynamics. Conversely, 82 host proteins were increased in or specific to mitochondria of infected cells, many of which act as anti-apoptotic factors and upregulators of cellular metabolism. These data support the notion that C. trachomatis specifically targets host mitochondria to manipulate cell fate decisions and metabolic function to support pathogen survival and replication. ImportanceObligate intracellular bacteria have evolved multiple means to promote their intracellular survival and replication within the otherwise harsh environment of the eukaryotic cell. Nutrient acquisition and avoidance of cellular defense mechanisms are critical to an intracellular lifestyle. Mitochondria are critical organelles that produce energy in the form of ATP and regulate programmed cell death responses to invasive pathogenic microbes. Cell death prior to completion of replication would be detrimental to the pathogen. C. trachomatis produces at least two and possibly more proteins that target the mitochondria. Collectively, C. trachomatis infection modulates mitochondrial protein composition favoring a profile suggestive of down-regulation of apoptosis.

microbiology↗