Orthoflavivirus nilense
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1320692 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Orthoflavivirus denguei Genome sequencing
| PRJNA1348690 | ENA
Project description:Orthoflavivirus denguei Raw sequence reads
| PRJNA1373386 | ENA
Project description:Flavivirus infection is tightly connected to host lipid metabolism. Here, we performed shotgun lipidomics of cells infected with neurotropic Zika, West Nile, and tick-borne encephalitis viruses, as well as dengue and yellow fever virus. Early in infection specific lipids accumulated, e.g., neutral lipids in Zika and some lyso-phospholipids in all infections. Ceramide levels increased following infection with viruses that cause a cytopathic effect. In addition, fatty acid desaturation as well as glycerophospholipid metabolism were significantly altered. Importantly, depletion of enzymes involved in phosphatidylserine metabolism as well as phosphatidylinositol biosynthesis reduced orthoflavivirus titers and cytopathic effects while inhibition of fatty acid monounsaturation only rescued from virus-induced cell death. Interestingly, interfering with ceramide synthesis had opposing effects on virus replication and cytotoxicity depending on the targeted enzyme. Thus, lipid remodeling by orthoflaviviruses includes distinct changes but also common patterns shared by several viruses that are needed for efficient infection and replication.
2024-09-03 | GSE264306 | GEO
Project description:Glycerophospholipid remodeling is critical for orthoflavivirus infection
| PRJNA1101937 | ENA
Project description:Orthoflavivirus infections represent an increasing public health burden, with several members of the genus emerging or re-emerging globally. Despite the availability of few vaccines, no antiviral drugs are currently licensed for the treatment of orthoflavivirus infections. Several pre-clinical studies identified the non-structural protein 4B (NS4B), one of the least characterized viral proteins within the orthoflavivirus genus, as the most promising target for the development of potent direct-acting antivirals. However, its functional roles in viral replication are still elusive. Here, we employ an integrated proteomic approach to systematically identify cellular targets of NS4B across eight prototypic orthoflaviviruses and characterize their influence on the human proteome. Using this approach, we mapped high-confidence NS4B-interacting human proteins across the genus, underlying potentially divergent mechanisms of host adaptation across orthoflaviviruses spanning diverse pathologies and vector preferences. Among these, we unveil a novel function for UBA5, the E1-activating enzyme of the UFMylation pathway, in orthoflavivirus replication. Mechanistically, we map associations of distinct viral proteins with multiple members of the UFMylation pathway, which are selectively recruited to sites of viral replication to promote mitochondrial respiration. Finally, we demonstrate that pharmacological inhibition of UFMylation exerts potent antiviral activity in vitro and in vivo. This integrative study provides a rational framework for a system-level understanding of orthoflavivirus NS4B effector functions and sheds light on a conserved and unconventional role for UFMylation in orthoflavivirus replication.
2026-03-10 | PXD063343 | Pride
Project description:Orthoflavivirus infections represent an increasing public health burden, with several members of the genus emerging or re-emerging globally. Despite the availability of few vaccines, no antiviral drugs are currently licensed for the treatment of orthoflavivirus infections. Several pre-clinical studies identified the non-structural protein 4B (NS4B), one of the least characterized viral proteins within the orthoflavivirus genus, as the most promising target for the development of potent direct-acting antivirals. However, its functional roles in viral replication are still elusive. Here, we employ an integrated proteomic approach to systematically identify cellular targets of NS4B across eight prototypic orthoflaviviruses and characterize their influence on the human proteome. Using this approach, we mapped high-confidence NS4B-interacting human proteins across the genus, underlying potentially divergent mechanisms of host adaptation across orthoflaviviruses spanning diverse pathologies and vector preferences. Among these, we unveil a novel function for UBA5, the E1-activating enzyme of the UFMylation pathway, in orthoflavivirus replication. Mechanistically, we map associations of distinct viral proteins with multiple members of the UFMylation pathway, which are selectively recruited to sites of viral replication to promote mitochondrial respiration. Finally, we demonstrate that pharmacological inhibition of UFMylation exerts potent antiviral activity in vitro and in vivo. This integrative study provides a rational framework for a system-level understanding of orthoflavivirus NS4B effector functions and sheds light on a conserved and unconventional role for UFMylation in orthoflavivirus replication.
2026-03-10 | PXD063404 | Pride
Project description:Flavivirus, Zika virus Genome sequencing and assembly
| PRJNA394139 | ENA
Project description:<p>Flavivirus infection is tightly connected to host lipid metabolism. Here, we performed shotgun lipidomics of cells infected with neurotropic Zika, West Nile and tick-borne encephalitis viruses, as well as dengue and yellow fever virus. Early in infection specific lipids accumulated, e.g., neutral lipids in Zika and some lyso-phospholipids in all infections. Ceramide levels increased following infection with viruses that cause a cytopathic effect. In addition, fatty acid desaturation as well as glycerophospholipid metabolism were significantly altered. Importantly, depletion of enzymes involved in phosphatidylserine metabolism as well as phosphatidylinositol biosynthesis reduced orthoflavivirus titers and cytopathic effects while inhibition of fatty acid monounsaturation only rescued from virus-induced cell death. Interestingly, interfering with ceramide synthesis had opposing effects on virus replication and cytotoxicity depending on the targeted enzyme. Thus, lipid remodeling by orthoflaviviruses includes distinct changes but also common patterns shared by several viruses that are needed for efficient infection and replication.</p>
2025-02-24 | MTBLS11030 | MetaboLights
Project description:Flavivirus infection is tightly connected to host lipid metabolism. Here, we performed shotgun lipidomics of cells infected with neurotropic Zika, West Nile, and tick-borne encephalitis virus, as well as dengue and yellow fever virus. Early in infection specific lipids accumulate, e.g., neutral lipids in Zika and some lysophospholipids in all infections. Ceramide levels increase following infection with viruses that cause a cytopathic effect. In addition, fatty acid desaturation as well as glycerophospholipid metabolism are significantly altered. Importantly, depletion of enzymes involved in phosphatidylserine metabolism as well as phosphatidylinositol biosynthesis reduce orthoflavivirus titers and cytopathic effects while inhibition of fatty acid monounsaturation only rescues from virus-induced cell death. Interestingly, interfering with ceramide synthesis has opposing effects on virus replication and cytotoxicity depending on the targeted enzyme. Thus, lipid remodeling by orthoflaviviruses includes distinct changes but also common patterns shared by several viruses that are needed for efficient infection and replication.
| S-EPMC11458896 | biostudies-literature