bioRxiv Science⌕ Search
Home/Archive/bioRxiv

bioRxiv · 10.1101/2025.04.21.648309

Modulation of viral replication, autophagy and apoptosis by induction and mutual regulation of transcription factors EB and E3 during coronavirus infection

Yang, B.·Fung, T. S.·Yuan, L.·Chen, R.·Liu, D.
View original source ↗Export metadata ↓

Abstract

Viral invasion of and replication in cells pose a significant impact on the structure and function of lysosomes. By sensing changes in the lysosome status, cascades of cellular responses are triggered to maintain the lysosomal homeostasis. Two key regulators, transcription factors EB (TFEB) and E3 (TFE3), play essential regulatory roles in these processes by shuttling between the cytoplasm and the nucleus. In this study, we report that infection of cells and/or chickens by gammacoronavirus infectious bronchitis virus (IBV), human betacoronavirus OC43 (HCoV-OC43), and alphacoronavirus porcine epidemic diarrhea virus (PEDV) upregulates the expression of TFEB/TFE3 as well as their downstream targets, and induces the lysosomal stress response. Knockdown of TFE3 alone or together with TFEB demonstrated a pronounced role played by TFE3 in regulating viral replication, virus-induced autophagy and apoptosis in cells infected with these viruses, and a synergistic effect of TFEB and TFE3 in regulation of these processes in cells infected with IBV and HCoV-OC43. Inhibition of the biosynthetic secretory pathway with brefeldin A (BFA) demonstrated that the release of HCoV-OC43 is mainly via the lysosomal pathway. This study provides novel insights into the functional roles of the lysosomal biogenesis and stress response in coronavirus replication and virus-host interactions. ImportanceIn recent years, more and more studies have shown that lysosomes function more than just as a recycling bin, they also play an important role as a hub for energy and signal transduction, autophagy regulation, and many physiological or pathological processes. This study showed that coronavirus infection activates lysosomal stress responses. As two transcription factors that regulate lysosomal biogenesis, TFEB and TFE3 regulate autophagy and apoptosis during the coronavirus replication cycle. In addition, it has been found that HCoV-OC43 releases viral particles through the lysosomal pathway, which may provide a new reference for the treatment of mitigating coronavirus infection.

Source connections

Explore related subjects

microbiologyPreprint

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Yang, B., Fung, T. S., Yuan, L., Chen, R., Liu, D.. 2025-04-23. Modulation of viral replication, autophagy and apoptosis by induction and mutual regulation of transcription factors EB and E3 during coronavirus infection. https://doi.org/10.1101/2025.04.21.648309

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

bioRxiv2026

Extreme temperature exposure has negative demographic consequences for Sulfolobus acidocaldarius

Microorganisms inhabiting geothermal springs and volcanic systems experience fluctuating temperatures that can periodically exceed their upper thermal limits, but the demographic consequences of such exposure remain poorly understood. Here, we investigated demographic responses of the thermophilic archaeon Sulfolobus acidocaldarius to an extreme temperature (94.1{degrees}C) under two regimes: sustained exposure varying in duration, and episodic exposure interspersed with recovery at a permissive temperature (75{degrees}C). Under sustained exposure, populations showed no detectable loss of viability after 15 min but declined thereafter, decreasing by approximately five orders of magnitude after 120 min. Under episodic exposure, populations remained viable across nine exposure-recovery cycles but declined in density with successive cycles. Similar responses were observed for three strains, including a DNA mismatch repair knockout ({Delta}nucS), indicating that mismatch repair deficiency did not affect viability or recovery. Together, these results demonstrate that S. acidocaldarius can withstand brief and repeated exposure to near-boiling temperatures, with mortality determined primarily by cumulative exposure duration rather than a fixed thermal threshold.

microbiology↗
bioRxiv2026

Bacteriophage and Antibiotic Resistance Are Positively Associated across a Phylogenetically Diverse Set of Clinical Pseudomonas aeruginosa Isolates

Co-administration of phages and antibiotics has been proposed as a therapeutic approach against antibiotic-resistant bacteria. The relationship, however, between antibiotic resistance and phage resistance in clinical isolates is unclear. Here, we examine associations between phage and antibiotic resistance profiles across a panel of Pseudomonas aeruginosa clinical isolates from the Centers for Disease Control (CDC) and Food and Drug Administration (FDA) Antimicrobial Resistance Isolate (ARI) Bank comprising 55 clinical strains with full genome sequences and antibiotic susceptibility testing (AST) data for 11 clinically relevant antibiotics. As phages in this study, we use three well-characterized, morphologically distinct phages, OMKO1, Luz19, and PAML31-1. We screen for phage resistance using a growth suppression assay, then conduct statistical analysis against antibiotic MIC (Minimum Inhibitory Concentration) data provided by the CDC to define association patterns across this dataset. We find multiple significant susceptibility correlations between pairs of antibiotics and phages, and a positive overall association between average phage resistance and antibiotic resistance across the 55 strains, even controlling for phylogenetic associations (=0.358, p<0.005). We conclude that phage and antibiotic resistance are positively associated across this clinical isolate collection, suggesting that the two resistance phenotypes are not independent in P. aeruginosa. These findings have implications for the development of phage-antibiotic cocktails.

microbiology↗
bioRxiv2026

The Estuary Effect: Variations in Temperature and Salinity Alter msh Promoter Activity in Vibrio cholerae

Vibrio cholerae, the facultative pathogen underlying cholera, naturally inhabits warm aquatic estuaries. Environmental persistence is enhanced by the ability of V. cholerae to colonize host reservoirs and form multicellular biofilms, causing seasonally endemic outbreaks in many tropical regions. Most toxigenic strains utilize the type IVa mannose-sensitive hemagglutinin (MSHA) pilus for host reservoir colonization and biofilm formation. Temperature and salinity can alter V. cholerae biofilm formation, yet their impact on MSHA production specifically remains largely unknown. Here, we utilized transcriptional reporters of predicted msh promoters (msh-P1/msh-P2/msh-P3) and functional assays, to determine temperature and salinity impacts on msh expression and pilus biogenesis. Under standard laboratory conditions (30{degrees}C, 1% NaCl) only msh-P1/P2 are active and inversely-coordinated with one another. Both msh-P1/P2 activity were elevated by high temperature (37{degrees}C) and low salinity (0.25%/0.5% NaCl), and reduced by low temperature (20{degrees}C/25{degrees}C) and high salinity (2%/3% NaCl). Temperature-mediated alterations in promoter activity were not immediately reflected in changes to cell-surface MSHA levels, whereas high salinity led to decreased MSHA production. Combining high temperature (37{degrees}C) and high salinity (2%/3% NaCl), attenuated the salinity-mediated reduction of msh-P1/P2 activity. Biofilm biomass levels were only substantially heightened at 25{degrees}C and 20{degrees}C, likely a result of no temperature-dependent changes in cell-surface MSHA, and additional temperature-controlled biofilm regulation previously described. We also found msh-P1/P2 promoter activity and MSHA production varies widely across toxigenic O1 and O139 serogroups despite complete sequence homology. These results shed new light on how key signals regulate MSHA pilus production to support V. cholerae persistence in aquatic environments.

microbiology↗