Exosomes are excretory nano-vesicles that are formed by the cell’s endocytic system and shed from the surface of almost all types of cells. These tiny extracellular vesicles, once thought to be “garbage bags for cells,” carry a wide variety of molecules of cellular origin, including proteins, lipids, and RNAs, that are selectively incorporated during the formation of exosomes. Exosomes are now known to play a central role in several important biological processes such as cellular communication, intercellular transfer of bioactive molecules, and immune modulation. Recent advances in the field have shown that a number of animal viruses can exploit the exosomal pathway by incorporating specific cellular or viral factors within exosomes, in order to modulate the cellular microenvironment and influence downstream processes such as host immunity and virus spread. In this chapter, we provide an overview of our current understanding of exosome biogenesis and how this normal physiological process is hijacked by some pathogenic viruses. Viral components that appear to be selectively incorporated into exosomes and the potential role of these exosomes in viral pathogenesis are discussed. Identifying viral signatures in exosomes and their mode of action is fundamental for any future diagnostic and therapeutic strategies for viral infections.
Virus | Main cellular target | Viral cargo reported in exosomes | Potential effect of viral exosomes |
---|---|---|---|
EBV | Lymphocytes | LMP1, 2A, gp350, vmiRNA, EBERs, vRNA | Proliferation, apoptosis, immune evasion, viral reactivation |
HSV-1 | Epithelial cells | VP16, HSV gB, ICP 127, vmiRNA | Increase infectivity, viral spread, and latency |
CMV | WBC, epithelial cells | CMV gB | Infection of myeloid dendritic cells, increased viral infectivity |
HHV-8 | WBC, endothelial cells | vmiRNA, vRNA | Immune modulation, cell metabolism |
HIV-1 | Lymphocytes | vmiRTAR, vmiRNA, Nef | Inhibition of apoptosis, stimulate proinflammatory cytokines, down-regulation of CD4 and MHC I, increased susceptibility of naïve T cells, antiviral activity |
HTLV-1 | Lymphocytes | Tax vmRNA, TAX, vmiRNA | Proinflammatory cytokines, damage to neurons |
HPV | Epithelial cells | vmiRNA | Proliferation, apoptosis |
HAV | Hepatocytes | HAV gRNA, HAV particles | Immune evasion, increased viral infectivity |
HBV | Hepatocytes | vDNA, vRNA, HBsAg | Immune evasion |
HCV | Hepatocytes | HCV gRNA, vmiRNA, vRNA | Immune evasion |
RVFV | WBC | v-protein, vmRNA | Apoptosis, immune evasion |
References
1.Functional delivery of viral miRNAs via exosomes
https://pubmed.ncbi.nlm.nih.gov/20304794/
2.Epstein-Barr virus-encoded small RNAs (EBERs) are present in fractions related to exosomes released by EBV-transformed cells
https://pubmed.ncbi.nlm.nih.gov/24896633/
3.Localization of the Epstein-Barr virus protein LMP 1 to exosomes
https://pubmed.ncbi.nlm.nih.gov/12810882/
4.Cholesterol is critical for Epstein-Barr virus latent membrane protein 2A trafficking and protein stability
https://pubmed.ncbi.nlm.nih.gov/17150237/
5.Exosomes containing glycoprotein 350 released by EBV-transformed B cells selectively target B cells through CD21 and block EBV infection in vitro
https://pubmed.ncbi.nlm.nih.gov/21106852/
6.Epstein-Barr virus-infected cells release Fas ligand in exosomal fractions and induce apoptosis in recipient cells via the extrinsic pathway
https://pubmed.ncbi.nlm.nih.gov/26467838/
7.Cells infected with herpes simplex virus 1 export to uninfected cells exosomes containing STING, viral mRNAs, and microRNAs
https://pubmed.ncbi.nlm.nih.gov/25368198/
8.The herpes simplex virus-1 encoded glycoprotein B diverts HLA-DR into the exosome pathway
https://pubmed.ncbi.nlm.nih.gov/19949097/
9.Pivotal advance: The promotion of soluble DC-SIGN release by inflammatory signals and its enhancement of cytomegalovirus-mediated cis-infection of myeloid dendritic cells
https://pubmed.ncbi.nlm.nih.gov/20940323/
10. Modulation of B-cell exosome proteins by gamma herpesvirus infection
https://pubmed.ncbi.nlm.nih.gov/23818640/
11. Profile of Exosomal and Intracellular microRNA in Gamma-Herpesvirus-Infected Lymphoma Cell Lines
https://pubmed.ncbi.nlm.nih.gov/27611973/
12. HIV-1 Nef protein is secreted into vesicles that can fuse with target cells and virions
https://pubmed.ncbi.nlm.nih.gov/18646314/
13. Nef neutralizes the ability of exosomes from CD4+ T cells to act as decoys during HIV-1 infection
https://pubmed.ncbi.nlm.nih.gov/25423108/
14. Latent HIV-1 is activated by exosomes from cells infected with either replication-competent or defective HIV-1
https://pubmed.ncbi.nlm.nih.gov/26502902/
15. Exosomes from HIV-1-infected Cells Stimulate Production of Pro-inflammatory Cytokines through Trans-activating Response (TAR) RNA
https://pubmed.ncbi.nlm.nih.gov/26553869/
16. Human T-lymphotropic virus type 1-infected cells secrete exosomes that contain Tax protein
https://pubmed.ncbi.nlm.nih.gov/24939845/
17. Extracellular human T-cell lymphotropic virus type I Tax protein induces cytokine production in adult human microglial cells
https://pubmed.ncbi.nlm.nih.gov/7979225/
18. Role of post-translational modifications of HTLV-1 Tax in NF-κB activation
https://pubmed.ncbi.nlm.nih.gov/21540989/
19. Dependence of intracellular and exosomal microRNAs on viral E6/E7 oncogene expression in HPV-positive tumor cells
https://pubmed.ncbi.nlm.nih.gov/25760330/
20. The Dual Role of Exosomes in Hepatitis A and C Virus Transmission and Viral Immune Activation
https://pubmed.ncbi.nlm.nih.gov/26694453/
21. Properties of subviral particles of hepatitis B virus
https://pubmed.ncbi.nlm.nih.gov/18524834/
22. A pathogenic picornavirus acquires an envelope by hijacking cellular membranes
https://pubmed.ncbi.nlm.nih.gov/23542590/
23. Subviral Hepatitis B Virus Filaments, like Infectious Viral Particles, Are Released via Multivesicular Bodies
https://pubmed.ncbi.nlm.nih.gov/26719264/
24. Exosomes mediate hepatitis B virus (HBV) transmission and NK-cell dysfunction
https://pubmed.ncbi.nlm.nih.gov/27238466/
25. Exosome-mediated transmission of hepatitis C virus between human hepatoma Huh7.5 cells
https://pubmed.ncbi.nlm.nih.gov/23878230/
26. Exosomes from hepatitis C infected patients transmit HCV infection and contain replication competent viral RNA in complex with Ago2-miR122-HSP90
https://pubmed.ncbi.nlm.nih.gov/25275643/
27. Short-range exosomal transfer of viral RNA from infected cells to plasmacytoid dendritic cells triggers innate immunity
https://pubmed.ncbi.nlm.nih.gov/23084922/
28. Presence of Viral RNA and Proteins in Exosomes from Cellular Clones Resistant to Rift Valley Fever Virus Infection
https://pubmed.ncbi.nlm.nih.gov/26904012/
https://www.intechopen.com/books/novel-implications-of-exosomes-in-diagnosis-and-treatment-of-cancer-and-infectious-diseases/exosomes-and-their-role-in-viral-infections