Occludin stalls HCV particle dynamics apart from hepatocyte tight junctions, promoting virion internalization

Deffieu, Maika S.; Clément, Camille M.H.; Dorobantu, Cristina M.; Partiot, Emma; Bare, Yonis; Faklaris, Orestis; Rivière, Benjamin; Ayala-Núñez, Nilda Vanesa; Baumert, Thomas F.; Rondé, Philippe; Lucansky, Vincent; Gaudin, Raphaël

doi:10.1002/hep.32514

Cited by 7 publications

(7 citation statements)

References 49 publications

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“…Indeed OCLN is an essential entry factor for HCV (39), which drives the dynamics of viral particle internalization (40). Unfortunately, we did not manage to get access to these proprietary antibodies targeting the Els of OCLN.…”

Section: Discussionmentioning

confidence: 99%

“…Antibodies targeting the extracellular domain of OCLN have been developed (38), as they represent an interesting strategy to block Hepatitis C virus (HCV) entry in hepatocytes. Indeed OCLN is an essential entry factor for HCV (39), which drives the dynamics of viral particle internalization (40). Unfortunately, we did not manage to get access to these proprietary antibodies targeting the Els of OCLN.…”

Section: Discussionmentioning

confidence: 99%

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Targeting monocytic Occludin impairs monocyte transmigration and HIV neuroinvasion

Brychka,

Ayala-Nunez,

Bare

et al. 2023

Preprint

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Transmigration of circulating monocytes from the bloodstream toward the central nervous system (CNS) represents a hallmark of neuroinflammation and plays an important role during viral encephalitis and HIV-associated neurocognitive disorders (HAND). The molecular mechanisms involved in monocyte transmigration through endothelia has been extensively studied, but how monocytes locally unzip tight junction-associated proteins (TJAPs) of the endothelium composing the neurovascular unit (NVU) to reach the CNS remains poorly understood. Here, we show that human circulating monocytes express the TJAP Occludin (OCLN) to promote transmigration through cerebral microvessel endothelial cells. Silencing monocytic OCLN (mOCLN) impairs monocyte transmigration, while mOCLN overexpression increases transmigration. Using high-resolution live cell imaging, we observed that mOCLN clusters at the monocyte-endothelium interface during the transmigration process, forming a transient ring of mOCLN at the site of diapedesis. Furthermore, we designed OCLN-derived peptides targeting its extracellular loop (EL) 1 or 2 to prevent potential trans-homotypic interactions of mOCLN with endothelial OCLN. We found that transmigration of human monocytes was significantly inhibited upon treatment with the EL2 peptidein vitroand in zebrafish embryos, while preserving vascular integrity. Monocyte transmigration toward the brain is an important process for HIV neuroinvasion and here, we showed that the treatment of transmigrating monocytes with the EL2 peptide prevents the dissemination of HIV to cerebral organoids. In conclusion, our study identifies an important role for monocytic OCLN during transmigration and provides a proof-of-concept for the development of mitigation strategies to prevent HIV neuroinvasion.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Targeting monocytic Occludin impairs monocyte transmigration and HIV neuroinvasion

Brychka,

Ayala-Nunez,

Bare

et al. 2023

Preprint

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“…Increasing evidence shows that these four genes are crucial for host resistance to multiple types of viral infections. IFIT5 is a factor in HCV entry, HCLS1 is a newly identified transcription regulator, and RSAD2 and IFIT5 are ISGs that have been shown to be critically important to resistance to viral infection, including influenza virus, HIV-1, and other viruses [34,35]. For example, RSAD2 performs its antiviral function by inhibiting the release of influenza virus through the JAK-STAT pathway mediated by type I/II IFN signaling [36,37].…”

Section: Discussionmentioning

confidence: 99%

Transcriptional Analysis of lncRNA and Target Genes Induced by Influenza A Virus Infection in MDCK Cells

Liu,

Pei,

Wang

et al. 2023

Vaccines

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Background: The MDCK cell line is the primary cell line used for influenza vaccine production. Using genetic engineering technology to change the expression and activity of genes that regulate virus proliferation to obtain high-yield vaccine cell lines has attracted increasing attention. A comprehensive understanding of the key genes, targets, and molecular mechanisms of viral regulation in cells is critical to achieving this goal, yet the post-transcriptional regulation mechanism involved in virus proliferation—particularly the effect of lncRNA on influenza virus proliferation—is still poorly understood. Therefore, this study used high-throughput RNA-seq technology to identify H1N1 infection-induced lncRNA and mRNA expression changes in MDCK cells and explore the regulatory relationship between these crucial lncRNAs and their target genes. Results: In response to H1N1 infection in MDCK cells 16 h post-infection (hpi) relative to uninfected controls, we used multiple gene function annotation databases and initially identified 31,501 significantly differentially expressed (DE) genes and 39,920 DE lncRNAs (|log2FC| > 1, p < 0.05). Among these, 102 lncRNAs and 577 mRNAs exhibited predicted correlations with viral response mechanisms. Based on the magnitude of significant expression differences, related research, and RT-qPCR expression validation at the transcriptional level, we further focused on 18 DE mRNAs and 32 DE lncRNAs. Among these, the differential expression of the genes RSAD2, CLDN1, HCLS1, and IFIT5 in response to influenza virus infection was further verified at the protein level using Western blot technology, which showed results consistent with the RNA-seq and RT-qPCR findings. We then developed a potential molecular regulatory network between these four genes and their six predicted lncRNAs. Conclusions: The results of this study will contribute to a more comprehensive understanding of the molecular mechanism of host cell non-coding RNA-mediated regulation of influenza virus replication. These results may also identify methods for screening target genes in the development of genetically engineered cell lines capable of high-yield artificial vaccine production.

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“…Likewise, the interaction of PLSCR1 with the HCV envelope proteins E1 and E2 also promotes viral entry. Additionally, PLSCR1 is necessary for the initial attachment of HCV to hepatic cells, where PLSCR1 interacts with the host cell entry factor occludin 45,46 …”

Section: Interaction Of Viruses With Phospholipids At the Cell Membranementioning

confidence: 99%

“…Additionally, PLSCR1 is necessary for the initial attachment of HCV to hepatic cells, where PLSCR1 interacts with the host cell entry factor occludin. 45,46 HIV-1 assembly occurs either on the plasma membrane or in the late endosome/multivesicular body (MVB) compartment. In cell types such as HeLa or T-cells, the majority of virus assembly takes place at the plasma membrane, while in primary macrophages, assembly occurs predominantly in late endosomes/MVBs.…”

Section: Proviral Functionsmentioning

confidence: 99%

Viruses and phospholipids: Friends and foes during infection

Rattay

Hufbauer

Hoboth

et al. 2023

Journal of Medical Virology

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Viruses have evolved complex and dynamic interactions with their host cells to enable viral replication. In recent years, insights have been gained into the increasingly important role of the host cell lipidome in the life cycle of several viruses. In particular, viruses target phospholipid signaling, synthesis, and metabolism to remodel their host cells into an optimal environment for their replication cycle. Conversely, phospholipids and their associated regulatory enzymes can interfere with viral infection or replication. This review highlights examples of different viruses that illustrate the importance of these diverse virus–phospholipid interactions in different cellular compartments, particularly the role of nuclear phospholipids and their association with human papillomavirus (HPV)‐mediated cancer development.

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Occludin stalls HCV particle dynamics apart from hepatocyte tight junctions, promoting virion internalization

Cited by 7 publications

References 49 publications

Targeting monocytic Occludin impairs monocyte transmigration and HIV neuroinvasion

Targeting monocytic Occludin impairs monocyte transmigration and HIV neuroinvasion

Transcriptional Analysis of lncRNA and Target Genes Induced by Influenza A Virus Infection in MDCK Cells

Viruses and phospholipids: Friends and foes during infection

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