Herpesviruses hijack host exosomes for viral pathogenesis
Section snippets
Extracellular vesicles
Extracellular vesicle (EV) is a broad term encompassing several vesicle types released from cells, that can be further categorised based on size [1], [2]. Apoptotic bodies (1000–5000 nm) are released from cells undergoing apoptosis [3], heterogeneous microvesicles and microparticles (100–1500 nm) can be shed from the plasma membrane [3], [4], [5], and homogenous exosomes (30–150 nm) can also be released from cells by mechanisms described below in Section 1.3 [6], [7]. EVs are secreted by most
Classification
HHVs of the Herpesviridae family emerged 180–220 million years ago [92]. At least eight species of herpesviruses have been found to infect humans, and can be classified into three subfamilies (Table 1). The α-herpesvirinae subfamily (HHV-1, HHV-2, HHV-3) includes HSV-1, HSV-2 and Varicella Zoster Virus (VZV). Herpesviruses are incurable, and only VZV is preventable with a vaccine. Approximately 90% of the world’s population is infected with one or both HSV [93], and can suffer from genital
HHV-1: herpes simplex virus 1
Assembly of herpesviruses has remained a hot topic in viral pathogenic research given the mechanisms are thought to have been conserved for at least 400 million years as the virus and host co-evolved [126]. HSV-1 virion maturation was reported to occur in the cytoplasm where secondary envelopment occurred within Golgi-derived vesicles [127], however the precise molecular mechanism were not characterised until 2007. A study by Crump, Yates, and Minson investigated host proteins involved in
Bridging gaps to understand the roles of exosomes in herpesvirus infection
The complexity of the extracellular microenvironment is supported by the diverse population of membranous vesicles that are continuously released by cells. This variation has confounded the EV field by causing the misinterpretation of data due to co-isolation of contaminating species (e.g. exosomes with shed microvesicles). To safeguard against this, the field has initiated establishing standardized protocols for EV isolation [20], as well as minimum data reporting [19]. These measures will
Concluding remarks
Herpesviruses have evolved elaborate mechanisms to acquire host cell exosomes for several aspects of viral infection. Despite ESCRT components TSG101 and ALIX being among the most studied for exosome biogenesis, herpesviruses do not always engage these for assembly. Rather, HSV-1, HCMV, and HHV-6 utilize other cellular machinery including VPS4, CD63, and CHMPs to promote secondary envelopment. As our knowledge broadens of ESCRT-independent pathways that can be used to generate exosomes, it is
Acknowledgements
Authors are supported, in part, by the National Health and Medical Research Council of Australia Project Grant APP1100737 (RAM), and Early Career CJ Martin FellowshipAPP1037043 (RAM).
References (163)
- et al.
Microparticles and infectious diseases
Médecine Maladies Infectieuses
(2012) Oncogenic H-ras reprograms Madin-Darby canine kidney (MDCK) cell-derived exosomal proteins following epithelial-mesenchymal transition
Mol. Cell Proteomics
(2013)- et al.
Comparison of ultracentrifugation: density gradient separation, and immunoaffinity capture methods for isolating human colon cancer cell line LIM1863-derived exosomes
Methods
(2012) - et al.
Selective enrichment of tetraspan proteins on the internal vesicles of multivesicular endosomes and on exosomes secreted by human B-lymphocytes
J. Biol. Chem.
(1998) Exosomes are released by cultured cortical neurones
Mol. Cell. Neurosci.
(2006)- et al.
Astrocytes secrete exosomes enriched with proapoptotic ceramide and prostate apoptosis response 4 (PAR-4): potential mechanism of apoptosis induction in Alzheimer disease (AD)
J. Biol. Chem.
(2012) - et al.
Reticulocyte maturation and exosome release: transferrin receptor containing exosomes shows multiple plasma membrane functions
Blood
(1989) - et al.
Transferrin recycling in reticulocytes: pH and iron are important determinants of ligand binding and processing
Biochem. Biophys. Res. Commun.
(1983) - et al.
Fate of the transferrin receptor during maturation of sheep reticulocytes in vitro: selective externalization of the receptor
Cell
(1983) - et al.
Two distinct populations of exosomes are released from LIM1863 colon carcinoma cell-derived organoids
Mol. Cell Proteomics
(2013)
The plasticity of multivesicular bodies and the regulation of antigen presentation
Semin. Cell Dev. Biol.
Exosomes–vesicular carriers for intercellular communication
Curr. Opin. Cell Biol.
Multivesicular bodies: co-ordinated progression to maturity
Curr. Opin. Cell Biol.
Biogenesis and secretion of exosomes
Curr. Opin. Cell Biol.
Exosomes–vesicular carriers for intercellular communication
Curr. Opin. Cell Biol.
Exosomes in viral disease
Neurotherapeutics
Roles for the recycling endosome: rab8, and Rab11 in hantavirus release from epithelial cells
Virology
Molecular phylogeny and evolutionary timescale for the family of mammalian herpesviruses
J. Mol. Biol.
Herpesvirus systematics
Vet. Microbiol.
The biogenesis and functions of exosomes
Traffic
Biological properties of extracellular vesicles and their physiological functions
J. Extracell. Vesicles
Biogenesis of extracellular vesicles (EV): exosomes, microvesicles, retrovirus-like vesicles, and apoptotic bodies
J. Neuro-Oncol.
Extracellular circulating viral microRNAs: current knowledge and perspectives
Front. Genet.
Regulation of immune responses by extracellular vesicles
Nat. Rev. Immunol.
Classification, functions, and clinical relevance of extracellular vesicles
Pharmacol. Rev.
Small RNA deep sequencing reveals a distinct miRNA signature released in exosomes from prion-infected neuronal cells
Nucl. Acids Res.
Tumour-derived microvesicles carry several surface determinants and mRNA of tumour cells and transfer some of these determinants to monocytes
Cancer Immunol. Immunother.
Extracellular vesicle-mediated transfer of a novel long noncoding RNA TUC339: a mechanism of intercellular signaling in human hepatocellular cancer
Genes Cancer
Intercellular nanovesicle-mediated microRNA transfer: a mechanism of environmental modulation of hepatocellular cancer cell growth
Hepatology
Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells
Nat. Cell Biol.
Glioblastoma microvesicles transport RNA and proteins that promote tumour growth and provide diagnostic biomarkers
Nat. Cell Biol.
Exosomes mediate the cell-to-cell transmission of IFN-alpha-induced antiviral activity
Nat. Immunol.
Cell to cell signalling via exosomes through esRNA
Cell Adhes. Migr.
Extracellular vesicle isolation and characterization: toward clinical application
J. Clin. Invest.
Minimal experimental requirements for definition of extracellular vesicles and their functions: a position statement from the International Society for Extracellular Vesicles
J. Extracell. Vesicles
Standardization of sample collection, isolation and analysis methods in extracellular vesicle research
J. Extracell. Vesicles
Microvesicles and viral infection
J. Virol.
Characterization of yeast extracellular vesicles: evidence for the participation of different pathways of cellular traffic in vesicle biogenesis
PLoS One
Klebsiella pneumoniae secretes outer membrane vesicles that induce the innate immune response
FEMS Microbiol. Lett.
TCR activation of human T cells induces the production of exosomes bearing the TCR/CD3/ζ complex
J. Immunol.
B lymphocytes secrete antigen-presenting vesicles
J. Exp. Med.
Molecular characterization of dendritic cell-derived exosomes: selective accumulation of the heat shock protein hsc73
J. Cell Biol.
Extracellular vesicles and a novel form of communication in the brain
Front. Neurosci.
Cytomegalovirus-Infected human endothelial cells can stimulate allogeneic CD4+ memory T cells by releasing antigenic exosomes
J. Immunol.
Characterization of secreted vesicles from vascular smooth muscle cells
Mol. Biosyst.
Oligodendrocytes secrete exosomes containing major myelin and stress-protective proteins: trophic support for axons?
Proteomics—Clin. Appl.
Exosomes and other extracellular vesicles in host-pathogen interactions
EMBO Rep.
Membrane vesicles as conveyors of immune responses
Nat. Rev. Immunol.
Microvesicles: ubiquitous contributors to infection and immunity
J. Leukoc. Biol.
Role of exosomes in immune regulation
J. Cell. Mol. Med.
Cited by (73)
NDV related exosomes enhance NDV replication through exporting NLRX1 mRNA
2021, Veterinary MicrobiologyCitation Excerpt :Hepatitis C virus (HCV) and Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) infected cells would secrete exosomes containing viral RNA, which can establish viral replication (Bukong et al., 2014; Wang et al., 2018). The exosomes secreted by Herpes Simplex Virus (HSV) infected cells would carry functional virus surface proteins to assist further virus infection (Sadeghipour and Mathias, 2017). Similarly, in our previous research, we found exosomes generated from NDV infected cells included viral protein NP, which promoted viral replication in recipient cells (Xu et al., 2019).
Size matters: Functional differences of small extracellular vesicle subpopulations in cardiac repair responses
2024, Journal of Extracellular VesiclesExtracellular Vesicles: a Trojan Horse Delivery Method for Systemic Administration of Oncolytic Viruses
2023, Regenerative Engineering and Translational MedicineIntrinsic factors behind long-COVID: II. SARS-CoV-2, extracellular vesicles, and neurological disorders
2023, Journal of Cellular Biochemistry