Exosome Biogenesis and Biological Function in Response to Viral Infections

Abstract

Introduction:Exosomes are extracellular vesicles that originate as intraluminal vesicles during the process of multivescular body formation. Exosomes mediate intercellular transfer of functional proteins, lipids, and RNAs. The investigation into the formation and role of exosomes in viral infections is still being elucidated. Exosomes and several viruses share similar structural and molecular characteristics.Explanation:It has been documented that viral hijacking exploits the exosomal pathway and mimics cellular protein trafficking. Exosomes released from virus-infected cells contain a variety of viral and host cellular factors that are able to modify recipient host cell responses. Recent studies have demonstrated that exosomes are crucial components in the pathogenesis of virus infection. Exosomes also allow the host to produce effective immunity against pathogens by activating antiviral mechanisms and transporting antiviral factors between adjacent cells.Conclusion:Given the ever-growing roles and importance of exosomes in both host and pathogen response, this review will address the impact role of exosome biogenesis and composition after DNA, RNA virus, on Retrovirus infections. This review also will also address how exosomes can be used as therapeutic agents as well as a vaccine vehicles.

A shared pathway of exosome biogenesis operates at plasma and endosome membranes

“…The model of exosome biogenesis posited here is also consistent with prior observations of exosome biogenesis via the plasma membrane (Anderson, 1969;Anderson et al, 2005;Bianchi et al, 2014;Booth et al, 2006;Cantaluppi et al, 2012;Casado et al, 2017;Fang et al, 2007;Shen et al, 2011a;Shen et al, 2011b) as well as prior observations of exosome biogenesis via endosome membranes (Colombo et al, 2014;Crenshaw et al, 2018;Desrochers et al, 2016;Harding et al, 1983;Harding et al, 1984;Mathew et al, 1995;Mathieu et al, 2019;Pan and Johnstone, 1983;Pegtel and Gould, 2019;van Niel et al, 2018). Furthermore, it adheres to the principle of maximum parsimony by offering a simpler explanation for a wider array of data than is possible under the 'endosome-only' hypothesis of exosome biogenesis.…”

“…A wide array of reviews and research articles assert that exosomes arise solely by budding into endosomes, followed by endosome-plasma membrane fusion (Colombo et al, 2014;Crenshaw et al, 2018;Desrochers et al, 2016;Mathieu et al, 2019;Thery et al, 2018;van Niel et al, 2018). We find this perplexing, in part because there is no compelling body of evidence that exosomes cannot bud from the plasma membrane, and in part because no study has even attempted to test this prevailing, 'endosome-only' hypothesis.…”

“…More recently, there has been a concerted effort to redefine these terms yet again, this time on the basis of biogenic mechanism. However, this effort has instead led to redefinition based on the site where an exosome originated in the cell, rather than the actual mechanism of biogenesis, and the now-commonplace dogma that that exosomes arise only by budding into the endosome lumen (Colombo et al, 2014;Crenshaw et al, 2018;Desrochers et al, 2016;Mathieu et al, 2019;van Niel et al, 2018). While there is abundant evidence that exosomes can arise in this manner, the prevailing, 'endosome-only' hypothesis of exosomes biogenesis is not supported by clear evidence that exosomes and exosome cargoes cannot bud from the plasma membrane.…”

“…This requires a focus on the most highly enriched exosomal proteins, as these show the strongest evidence of active sorting into exosomes, which are the tetraspanins CD63, CD9, and CD81 (Escola et al, 1998;Thery et al, 1999), a trio of proteins that are widely used as exosome markers (Colombo et al, 2014;Crenshaw et al, 2018;Desrochers et al, 2016;Mathieu et al, 2019;van Niel et al, 2018). Like all tetraspanins, these proteins are cotranslationally translocated into the ER lumen and membrane, span the membrane 4 times, and have their N-terminus and C-terminus oriented into the cytoplasm.…”

Exploring the Relevance of Senotherapeutics for the Current SARS-CoV-2 Emergency and Similar Future Global Health Threats

“…Senescent cells secrete EVs with a distinctive, but still incompletely characterized, content of miRNA, proteins, and DNA that can spread senescence in surrounding and even distant tissues [44][45][46][47], thus promoting further inflammation and catastrophic consequences for the organism [48]. Interestingly, it has been documented that exosomes are crucial components in the pathogenesis of virus infection, but specific studies for SARS-CoV or SARS-CoV are still lacking [49].…”