Hepatitis virus hijacks shuttle: Exosome-like vesicles provide protection against neutralizing antibodies

Ramakrishnaiah, Vedashree; Laan, Luc J. W. van der

doi:10.1002/hep.26943

Cited by 11 publications

(9 citation statements)

References 15 publications

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“…Studies have shown that exosomes secreted by host cells play an important role in host viral infection. Exosomes play a dual role in the body's immune response, they spread and proliferate the virus [43][44][45] as well as promote host immunosuppression [46]. Studies have found that, in addition to the traditional recognition mechanism, infected cells can secrete exosomes to transfer viral contents to other uninfected cells [47].…”

Section: Discussionmentioning

confidence: 99%

Exosomes Transmit Viral Genetic Information and Immune Signals may cause Immunosuppression and Immune Tolerance in ALV-J Infected HD11 cells

Wang

et al. 2020

Int. J. Biol. Sci.

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Avian leukosis virus (ALV) is oncogenic retrovirus that not only causes immunosuppression but also enhances the host's susceptibility to secondary infection. Exosomes play vital role in the signal transduction cascades that occur in response to viral infection. We want to explore the function of exosomes in the spread of ALV and the body's subsequent immunological response. RNA-sequencing and the isobaric tags for relative and absolute quantitation (iTRAQ) method were used to detect differentially expressed genes (DEGs) and differentially expressed proteins (DEPs) in exosomes secreted by macrophage cells in response to injection with ALV subgroup J (ALV-J). RNA-sequencing identified 513 DEGs in infected cells, with specific differential regulation in mRNA involved in tight junction signaling, TNF signaling, salmonella infection response, and immune response, among other important cellular processes. Differential regulation was observed in 843 lncRNAs, with particular enrichment in those lncRNA targets involved in Rap1 signaling, HTLV-I infection, tight junction signaling, and other signaling pathways. A total of 50 DEPs were identified in the infected cells by iTRAQ. The proteins enriched are involved in immune response, antigen processing, the formation of both MHC protein and myosin complexes, and transport. Combined analysis of the transcriptome and proteome revealed that there were 337 correlations between RNA and protein enrichment, five of which were significant. Pathways that were enriched on both the RNA and protein levels were involved in pathways in cancer, PI3K-Akt signaling pathway, Endocytosis, Epstein-Barr virus infection. These data show that exosomes are transmitters of intercellular signaling in response to viral infection. Exosomes can carry both viral nucleic acids and proteins, making it possible for exosomes to be involved in the viral infection of other cells and the transmission of immune signals between cells. Our sequencing results confirme previous studies on exosomes and further find exosomes may cause immunosuppression and immune tolerance.

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Section: Discussionmentioning

confidence: 99%

Exosomes Transmit Viral Genetic Information and Immune Signals may cause Immunosuppression and Immune Tolerance in ALV-J Infected HD11 cells

Wang

et al. 2020

Int. J. Biol. Sci.

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“…As former ILVs form by inward budding of the LE/MVB-limiting membrane, exosomes are thought to expose PtdSer, an apoptotic marker, on the external leaflet of the membrane and initiate PtdSer receptor-engaged uptake (48). Apoptotic mimicry has been used by hepatotropic hepatitis A virus (HAV) for infection, in which the virus is cloaked in a PtdSer-containing envelope by hijacking the exosome secretion pathway and entering target cells via TIM-1-mediated internalization (27,49,50). Although PtdSer is generally expressed on the external membrane of exosomes from different cell types, TIM-1 uniquely mediated the entry of macrophage-derived exosomes into hepatocytes.…”

Section: Discussionmentioning

confidence: 99%

Exosomes Exploit the Virus Entry Machinery and Pathway To Transmit Alpha Interferon-Induced Antiviral Activity

Yao

Qiao

et al. 2018

J Virol

103

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Alpha interferon (IFN-α) induces the transfer of resistance to hepatitis B virus (HBV) from liver nonparenchymal cells (LNPCs) to hepatocytes via exosomes. However, little is known about the entry machinery and pathway involved in the transmission of IFN-α-induced antiviral activity. In this study, we found that macrophage exosomes uniquely depend on T cell immunoglobulin and mucin receptor 1 (TIM-1), a hepatitis A virus (HAV) receptor, to enter hepatocytes for delivering IFN-α-induced anti-HBV activity. Moreover, two primary endocytic routes for virus infection, clathrin-mediated endocytosis (CME) and macropinocytosis, collaborate to permit exosome entry and anti-HBV activity transfer. Subsequently, lysobisphosphatidic acid (LBPA), an anionic lipid closely related to endosome penetration of virus, facilitates membrane fusion of exosomes in late endosomes/multivesicular bodies (LEs/MVBs) and the accompanying exosomal cargo uncoating. Together, our findings provide comprehensive insights into the transmission route of macrophage exosomes to efficiently deliver IFN-α-induced antiviral substances and highlight the similarities between the entry mechanisms of exosomes and virus.IMPORTANCE Our previous study showed that LNPC-derived exosomes could transmit IFN-α-induced antiviral activity to HBV replicating hepatocytes, but the concrete transmission mechanisms, which include exosome entry and exosomal cargo release, remain unclear. In this study, we found that virus entry machinery and pathway were also applied to exosome-mediated cell-to-cell antiviral activity transfer. Macrophage-derived exosomes distinctively exploit hepatitis A virus receptor for access to hepatocytes. Later, CME and macropinocytosis are utilized by exosomes, followed by exosome-endosome fusion for efficient transfer of IFN-α-induced anti-HBV activity. We believe that understanding the cellular entry pathway of exosomes will be beneficial to designing exosomes as efficient vehicles for antiviral therapy.

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“…Studies have shown that the mechanism of HAV infection is related to exosomes. Ramakrishnaiah et al reported that the HAV can hide in the exosomes membrane to escape the host immune response, survive in the blood, cause corresponding lesions, and possibly promote the spread of the virus in the liver [ 66 ]. Feng et al found that HAV released from cells is masked by host-derived membranes, and viral particles can be engulfed by exosome-like host membranes to form enveloped viruses, thereby protecting virions from antibody-mediated neutralization [ 67 ].…”

Section: Exosomes and Digestive System Inflammatory Diseasesmentioning

confidence: 99%

Exosome-mediated effects and applications in inflammatory diseases of the digestive system

Xiang

et al. 2022

Eur J Med Res

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Exosomes are membranous vesicles containing RNA and proteins that are specifically secreted in vivo. Exosomes have many functions, such as material transport and signal transduction between cells. Many studies have proven that exosomes can not only be used as biomarkers for disease diagnosis but also as carriers to transmit information between cells. Exosomes participate in a variety of physiological and pathological processes, including the immune response, antigen presentation, cell migration, cell differentiation, and tumour development. Differences in exosome functions depend on cell type. In recent years, exosome origin, cargo composition, and precise regulatory mechanisms have been the focus of research. Although exosomes have been extensively reported in digestive tumours, few articles have reviewed their roles in inflammatory diseases of the digestive system, especially inflammatory-related diseases (such as reflux oesophagitis, gastritis, inflammatory bowel disease, hepatitis, and pancreatitis). This paper briefly summarizes the roles of exosomes in inflammatory diseases of the digestive system to provide a basis for research on the mechanism of inflammatory diseases of the digestive system targeted by exosomes.

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Hepatitis virus hijacks shuttle: Exosome-like vesicles provide protection against neutralizing antibodies

Cited by 11 publications

References 15 publications

Exosomes Transmit Viral Genetic Information and Immune Signals may cause Immunosuppression and Immune Tolerance in ALV-J Infected HD11 cells

Exosomes Transmit Viral Genetic Information and Immune Signals may cause Immunosuppression and Immune Tolerance in ALV-J Infected HD11 cells

Exosomes Exploit the Virus Entry Machinery and Pathway To Transmit Alpha Interferon-Induced Antiviral Activity

Exosome-mediated effects and applications in inflammatory diseases of the digestive system

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