Enterovirus D68 (EV-D68) is a respiratory pathogen associated with acute flaccid myelitis, a childhood paralysis disease. No approved vaccine or antiviral treatment exists against EV-D68. Infection with this virus induces the formation of autophagosomes to enhance its replication but blocks the downstream autophagosome- lysosome fusion steps. Here, we examined the impact of autophagy induction through starvation, either before (starvation before infection, SBI) or after (starvation after infection, SAI) EV-D68 infection. We showed that SAI, but not SBI, attenuated EV-D68 replication in multiple cell lines and abrogated the viral-mediated cleavage of host autophagic flux-related proteins. Furthermore, SAI induced autophagic flux during EV-D68 replication and prevented production of virus-induced membranes, which are required for picornavirus replication. Pharmacological inhibition of autophagic flux during SAI did not rescue EV-D68 titers. SAI had the same effect in multiple cell types, and restricted the replication of several medically relevant picornaviruses. Our results highlight the significance of autophagosomes for picornavirus replication and identify SAI as an attractive broad-spectrum anti-picornavirus strategy. BAF: bafilomycin A; CCCP: carbonyl cyanide m-chlorophenylhydrazone; CQ: chloroquine; CVB3: coxsackievirus B3; EV-D68: enterovirus D68; hpi: hour post-infection; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; MOI: multiplicity of infection; NSP2B: nonstructural protein 2B; PV: poliovirus; RES: resveratrol; RV14: rhinovirus 14; SAI: starvation after infection; SBI: starvation before infection; SNAP29: synaptosome associated protein 29; SQSTM1/p62: sequestosome 1; TFEB: transcription factor EB.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9809931 | PMC |
| http://dx.doi.org/10.1080/15548627.2022.2062888 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Effect of tryptophan starvation on inclusion membrane composition and chlamydial-host interactions.
Infect Immun
January 2025
Department of Pathology, Microbiology, and Immunology, College of Medicine, University of Nebraska Medical Center, Omaha, Nebraska, USA.
is an obligate intracellular bacterial pathogen that develops within a membrane-bound vacuole called an inclusion. Throughout its developmental cycle, modifies the inclusion membrane (IM) with type III secreted (T3S) membrane proteins, known as inclusion membrane proteins (Incs). Via the IM, manipulates the host cell to acquire lipids and nutrients necessary for its growth.
View Article and Find Full Text PDFChronic bacterial infections exert metabolic costs in Drosophila melanogaster.
J Exp Biol
January 2025
Department of Entomology, Cornell University, Ithaca, NY 14853, USA.
Bacterial infections can substantially impact host metabolic health as a result of the direct and indirect demands of sustaining an immune response and of nutrient piracy by the pathogen itself. Drosophila melanogaster and other insects that survive a sublethal bacterial infection often carry substantial pathogen burdens for the remainder of life. In this study, we asked whether these chronic infections exact metabolic costs for the host, and how these costs scale with the severity of chronic infection.
View Article and Find Full Text PDFMitochondria and the Repurposing of Diabetes Drugs for Off-Label Health Benefits.
Int J Mol Sci
January 2025
Department of Microbiology & Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, Singapore.
This review describes our current understanding of the role of the mitochondria in the repurposing of the anti-diabetes drugs metformin, gliclazide, GLP-1 receptor agonists, and SGLT2 inhibitors for additional clinical benefits regarding unhealthy aging, long COVID, mental neurogenerative disorders, and obesity. Metformin, the most prominent of these diabetes drugs, has been called the "Drug of Miracles and Wonders," as clinical trials have found it to be beneficial for human patients suffering from these maladies. To promote viral replication in all infected human cells, SARS-CoV-2 stimulates the infected liver cells to produce glucose and to export it into the blood stream, which can cause diabetes in long COVID patients, and metformin, which reduces the levels of glucose in the blood, was shown to cut the incidence rate of long COVID in half for all patients recovering from SARS-CoV-2.
View Article and Find Full Text PDFMaternal effects in the model system Daphnia: the ecological past meets the epigenetic future.
Heredity (Edinb)
January 2025
Department of Biological Sciences, University of South Carolina, Columbia, SC, USA.
Maternal effects have been shown to play influential roles in many evolutionary and ecological processes. However, understanding how environmental stimuli induce within-generation responses that transverse across generations remains elusive, particularly when attempting to segregate confounding effects from offspring genotypes. This review synthesizes literature regarding resource- and predation-driven maternal effects in the model system Daphnia, detailing how the maternal generation responds to the environmental stimuli and the maternal effects seen in the offspring generation(s).
View Article and Find Full Text PDFFatal and sp. co-infestation in wolves () at the Białowieża National Park, Poland - is it a consequence of climate change?
J Vet Res
December 2024
Department of Virology, National Veterinary Research Institute, 24-100 Puławy, Poland.
Introduction: In winter 2021/2022, a wolf population in the primeval Białowieża Forest in Poland was struck by an outbreak of severe mange caused by mixed infestations of and mites. We present an epidemiological analysis of this mange which caused significant morbidity and mortality.
Material And Methods: Ten sites known for wolf activity were monitored by camera trapping.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!