ADP-ribosylation Factor-related Protein 1 Interacts with NS5A and Regulates Hepatitis C Virus Propagation

Lim, Yun-Sook; Ngo, Huong Thi Thanh; Lee, Jihye; Son, Kidong; Park, Eun-Mee; Hwang, Soon B.

doi:10.1038/srep31211

Cited by 10 publications

(5 citation statements)

References 31 publications

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“…Therefore, the recruitment of Arf proteins to the inner pre-AC could be one of the reasons for the reorganization and accumulation of the expanded membranous elements of the EE, ERC, and EE-ERC interface in the pericentriolar region of MCMV-infected cells and are therefore important for the biogenesis of pre-AC. Although the activation and recruitment of Arf GTPases on replication organelles have been reported after infection with different viruses [ 82 , 83 , 84 , 85 , 86 , 87 , 88 ], their importance in the biogenesis of pre-AC in MCMV-infected cells is understudied.…”

Section: Discussionmentioning

confidence: 99%

Arf GTPases Are Required for the Establishment of the Pre-Assembly Compartment in the Early Phase of Cytomegalovirus Infection

Pavišić

Lučin

Zagorac

et al. 2021

Life

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Shortly after entering the cells, cytomegaloviruses (CMVs) initiate massive reorganization of cellular endocytic and secretory pathways, which results in the forming of the cytoplasmic virion assembly compartment (AC). We have previously shown that the formation of AC in murine CMV- (MCMV) infected cells begins in the early phase of infection (at 4–6 hpi) with the pre-AC establishment. Pre-AC comprises membranes derived from the endosomal recycling compartment, early endosomes, and the trans-Golgi network, which is surrounded by fragmented Golgi cisterns. To explore the importance of Arf GTPases in the biogenesis of the pre-AC, we infected Balb 3T3 cells with MCMV and analyzed the expression and intracellular localization of Arf proteins in the early phases (up to 16 hpi) of infection and the development of pre-AC in cells with a knockdown of Arf protein expression by small interfering RNAs (siRNAs). Herein, we show that even in the early phase, MCMVs cause massive reorganization of the Arf system of the host cells and induce the over-recruitment of Arf proteins onto the membranes of pre-AC. Knockdown of Arf1, Arf3, Arf4, or Arf6 impaired the establishment of pre-AC. However, the knockdown of Arf1 and Arf6 also abolished the establishment of infection. Our study demonstrates that Arf GTPases are required for different steps of early cytomegalovirus infection, including the establishment of the pre-AC.

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Section: Discussionmentioning

confidence: 99%

Arf GTPases Are Required for the Establishment of the Pre-Assembly Compartment in the Early Phase of Cytomegalovirus Infection

Pavišić

Lučin

Zagorac

et al. 2021

Life

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“…Knockdown of SNAP23 with siRNA reduces LD-mitochondria interactions and β-oxidation [56]. Additionally, ADP-ribosylation factor related protein 1 (ARFRP1) recruits SNAP23 near LDs, promoting LD growth in hepatitis C virus-infected cells, suggesting SNAP23's role in LD amplification [58].…”

Section: Mechanisms Of Ld-mitochondria Contactsmentioning

confidence: 99%

Lipid Droplet–Mitochondria Contacts in Health and Disease

Fan,

Tan

2024

IJMS

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The orchestration of cellular metabolism and redox balance is a complex, multifaceted process crucial for maintaining cellular homeostasis. Lipid droplets (LDs), once considered inert storage depots for neutral lipids, are now recognized as dynamic organelles critical in lipid metabolism and energy regulation. Mitochondria, the powerhouses of the cell, play a central role in energy production, metabolic pathways, and redox signaling. The physical and functional contacts between LDs and mitochondria facilitate a direct transfer of lipids, primarily fatty acids, which are crucial for mitochondrial β-oxidation, thus influencing energy homeostasis and cellular health. This review highlights recent advances in understanding the mechanisms governing LD–mitochondria interactions and their regulation, drawing attention to proteins and pathways that mediate these contacts. We discuss the physiological relevance of these interactions, emphasizing their role in maintaining energy and redox balance within cells, and how these processes are critical in response to metabolic demands and stress conditions. Furthermore, we explore the pathological implications of dysregulated LD–mitochondria interactions, particularly in the context of metabolic diseases such as obesity, diabetes, and non-alcoholic fatty liver disease, and their potential links to cardiovascular and neurodegenerative diseases. Conclusively, this review provides a comprehensive overview of the current understanding of LD–mitochondria interactions, underscoring their significance in cellular metabolism and suggesting future research directions that could unveil novel therapeutic targets for metabolic and degenerative diseases.

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“…Of note, these transcripts contained several proteins involved in viral replication, such as ADP-ribosylation factor-related protein 1 (ARFRP1) and ceramide synthase 5 (CERS5). ARFRP1 interacted with NS5A, and silencing of ARFRP1 dramatically restrained HCV replication in both subgenomic replicon cells and HCVcc-infected cells [ 18 ]. Ceramide, a bioactive sphingolipid associated with signalling and apoptosis, was required for ZIKV infection and closely associated with ZIKV NS4B [ 19 ].…”

Section: Zikv Infections Evaded the Activation Of Immune-related Genesmentioning

confidence: 99%

Identification of novel anti-ZIKV drugs from viral-infection temporal gene expression profiles

Zhang

Tan

Wei

et al. 2023

Emerging Microbes & Infections

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Zika virus (ZIKV) infections are typically asymptomatic but cause severe neurological complications (e.g. Guillain–Barré syndrome in adults, and microcephaly in newborns). There are currently no specific therapy or vaccine options available to prevent ZIKV infections. Temporal gene expression profiles of ZIKV-infected human brain microvascular endothelial cells (HBMECs) were used in this study to identify genes essential for viral replication. These genes were then used to identify novel anti-ZIKV agents and validated in publicly available data and functional wet-lab experiments. Here, we found that ZIKV effectively evaded activation of immune response-related genes and completely reprogrammed cellular transcriptional architectures. Knockdown of genes, which gradually upregulated during viral infection but showed distinct expression patterns between ZIKV- and mock infection, discovered novel proviral and antiviral factors. One-third of the 74 drugs found through signature-based drug repositioning and cross-reference with the Drug Gene Interaction Database (DGIdb) were known anti-ZIKV agents. In cellular assays, two promising antiviral candidates (Luminespib/NVP-AUY922, L-161982) were found to reduce viral replication without causing cell toxicity. Overall, our time-series transcriptome-based methods offer a novel and feasible strategy for antiviral drug discovery. Our strategies, which combine conventional and data-driven analysis, can be extended for other pathogens causing pandemics in the future.

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ADP-ribosylation Factor-related Protein 1 Interacts with NS5A and Regulates Hepatitis C Virus Propagation

Cited by 10 publications

References 31 publications

Arf GTPases Are Required for the Establishment of the Pre-Assembly Compartment in the Early Phase of Cytomegalovirus Infection

Arf GTPases Are Required for the Establishment of the Pre-Assembly Compartment in the Early Phase of Cytomegalovirus Infection

Lipid Droplet–Mitochondria Contacts in Health and Disease

Identification of novel anti-ZIKV drugs from viral-infection temporal gene expression profiles

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