Table 1.

Exosomes’ biogenesis and their roles in pathogenesis, medical usefulness, and applications in viral infection.

Viruses	Viral Cargo	Cellular Target	Exosome Biogenesis	Exosomes Roles in the Pathogenesis	Medical Usefulness and Applications	References
Adenovirus	mRNA and miRNA	dendritic cells	Developing of early endosome	Attaching of cell surface receptors onto host cells	The host body of HIV-1 inspires to be clear of viral factors by releasing them into exosomes	[15,77]
HSV-1	VP16, Heat shock proteins, HSV gB, ICP 127, miRNA	Epithelial cells	Trafficking proteins, DNA, RNA and lipids	Delivering of suppressed membrane protein 1 (LMP1) to host cells	Exosomes suppress or stimulate the immune response (immunomodulators)	[15,78,79,80,81,82,83]
Ebola	DNA	macrophage, dendritic cells,	early endosome development	Cell surface receptors Attachment	Clearing the host bodies from virions	[84,85]
EBV	RNA, miRNA, LMP1, 2A, gp350, EBERs	Lymphocytes	budding of endosomal multivesicular bodies	Proliferation, viral reactivation apoptosis, immune evasion	Intercellular communication between cells of the immune system	[86,87,88,89,90,91]
HCV	miRNA, CD9, CD63, CD 81, HCV gRNA, RNA	Hepatocytes	receptor-mediated endocytosis, and plasma membrane fusion	viral maturation and immune evasion	Neutralizing antibodies are resistant to HCV transmission by exosomes as a potential immune evasion mechanism.	[92,93,94]
Dengue virus	Immunoregulator molecules (MHCI and MCII)	Monocytes, macrophages	Recruit ESCRTs to the endosomal membrane	Assembly, transfer of viral RNAs, and suppression of immune activation.	Development of antiviral and vaccine candidate	[95]
HPV	immunoregulator molecules, miRNA	Epithelial cells	ESCRTs are delivered to the site of budding	Apoptosis, viral proliferation,	Promoting anti-apoptotic potential.	[96]
CMV	CMV gB	WBC, epithelial cells	Stimulating membrane budding	Improved viral pathogenicity, infection of myeloid dendritic cells	Inflammatory and regulatory markers	[97]
polyomaviruses, (JCPyV and BKPyV)	Virion particles and miRNA	kidney, bone marrow, and central nervous system (CNS)	Virions packaged within EVs and associated to vesicles surface	play a key role in the dissemination and spread of polyomaviruses	Enhanced viral transmission and can be used as biomarker	[98,99,100,101]
Coxsackievirus B1	Replication competent genome within EV	Epithelial cells	Increased EV biogenesis	Increase viral spread	prolonged viral replication through micro RNA packaged in exosomes and can be used biomarker	[102]
Chikungna virus	apoptotic bodies	Skeletal muscles, brain, and liver cells	hijacking apoptotic bodies	Infectious virions hijacking apoptotic bodies. Increased viral spread	Increased viral spread and can be used as biomarker	[103]
ZIKV	Macrophage-derived exosomes	Brain, skin, placenta, retina, testis, and kidney cells	Infection significantly increases EV formation	Induction of placental proinflammatory cytokine production.	EVs derived from the semen of a ZIKV-infected patient inhibited ZIKV and delivering therapeutics across brain barriers
	ZIKV NS5-mediated activation of NLRP3			Activation of host inflammatory response and macrophage recruitment promotes inflammation		[104,105]
	EV-bound ZIKV-RNA and E-protein			Increased ZIKV transmission across neurons		[106]
HIV	Cytoskeletal proteins (Actin, Tubulin, Lamin, Myosin)miRTAR, miRNA, Nef	Lymphocytes	ESCRT I and IIenhance membrane budding	Induce proinflammatory cytokines, inhibition of apoptosis, increased susceptibility of naïve T cells, downregulation of CD4 and MHC I, Support viral reproduction and pathogenesis	Analytical indicators in HIV-1, antiviral activity	[107,108,109,110,111]
HBV	HBsAg, DNA, RNA	Hepatocytes	Multivesicular bodies fuse with the plasma membrane and secrete exosomes	Innate immunity evasion, transmission regulators	Drug delivery candidates for the targeted or systematic vehicle to particular organs or tissues	[14,112,113]
HAV	HAV particles, enzymes, HAV gRNA,	Hepatocytes	Transport of ESCRT III, VPS4B, and ALIX. through endosomal-sorting complexes	Increasing viral infectivity, innate immunity evasion, intercellular communications	Drug delivery candidates for the targeted or systematic vehicle to particular organs or tissues	[114]
Rift Valley fever virus	Viral proteins, miRNA, mRNA	WBC	ESCRTs enhance membrane budding	Immune evasion, apoptosis, enhance viral infectivity	Analytic indicators	[115]
human T-lymphotropic virus	mRNA, miRNA, trans-activator protein	Lymphocytes	ESCRTs Stimulate membrane budding	Activate cytokines, damage to neurons, increase viral replication	Contribute to the pathology of the viral infection	[116,117,118]
HHV-8	RNA, miRNA	endothelial cells, WBC	budding of endosomal multivesicular bodies	cell metabolism, immune modulation	Intercellular communication between cells of the immune system	[119,120]