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Review
. 2020 Nov:85:104422.
doi: 10.1016/j.meegid.2020.104422. Epub 2020 Jun 13.

The role of extracellular vesicles in COVID-19 virus infection

Mehdi Hassanpour  1 , Jafar Rezaie  2 , Mohammad Nouri  1 , Yunes Panahi  3
Affiliations
Review

The role of extracellular vesicles in COVID-19 virus infection

Mehdi Hassanpour et al. Infect Genet Evol. 2020 Nov.

Abstract

Extracellular vesicles releasing from various types of cells contribute to intercellular communication via delivering bio-molecules like nucleic acids, proteins, and lipids to recipient cells. Exosomes are 30-120 nm extracellular vesicles that participate in several pathological conditions. Virus-infected cells release exosomes that are implicated in infection through transferring viral components such as viral-derived miRNAs and proteins. As well, exosomes contain receptors for viruses that make recipient cells susceptible to virus entry. Since December 2019, SARS-CoV-2 (COVID-19) infection has become a worldwide urgent public health concern. There is currently no vaccine or specific antiviral treatment existing for COVID-19 virus infection. Hence, it is critical to find a safe and effective therapeutic tool to patients with severe COVID-19 virus infection. Extracellular vesicles may contribute to spread this virus as they transfer such receptors as CD9 and ACE2, which make recipient cells susceptible to virus docking. Upon entry, COVID-19 virus may be directed into the exosomal pathway, and its component is packaged into exosomes for secretion. Exosome-based strategies for the treatment of COVID-19 virus infection may include following items: inhibition of exosome biogenesis and uptake, exosome-therapy, exosome-based drug delivery system, and exosome-based vaccine. Mesenchymal stem cells can suppress nonproductive inflammation and improve/repair lung cells including endothelial and alveolar cells, which damaged by COVID-19 virus infection. Understanding molecular mechanisms behind extracellular vesicles related COVID-19 virus infection may provide us with an avenue to identify its entry, replication, spreading, and infection to overcome its adverse effects.

Keywords: COVID-19 virus; Exosomes; Extracellular vesicles; Viral infection.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Fig. 1
Fig. 1
Biogenesis of exosomes and microvesicles (MVs) in virus-infected cells. Exosomes originating from multivesicular bodies (MVBs) located in the cytoplasm, while MVs shedding from the plasma membrane of cells. Exosomes/MVs can reach to target cells by the three possible ways including internalization, direct-fusion, and receptor-ligand interaction. Viruses can entry onto host cells via direct fusion and endocytosis (1). After entry, viruses may be uncoated or/and sorted into MVBs/exosomes (2) and viral component can be directed into nucleus or/and translated into proteins (3). Translated products may assemble (5) or /and enter EE and GA; and finally are sorted into MVBs/exosomes (6). Alternatively, after assembly, viral components may be directed into MVs (6). CMV: Cytomegalovirus; EBV: Epstein–Barr virus; EE: early endosomes; ER: Endoplasmic Reticulum; HCV: Hepatitis C virus; HIV: Human immunodeficiency virus; HSV1: Herpes simplex virus; KSHV: Kaposi's sarcoma-associated herpesvirus.
Fig. 2
Fig. 2
The coronavirus disease 19 (COVID-19) life cycle in human lung cells. COVID-19 entry into cells when S protein binds to ACE2 receptor (1). After docking, the S protein conformation is changed, which facilitates virus entry into the endosomal pathway (2). Then, COVID-19 virus releases RNA into the cell or/and COVID-19 virus components may be directed into MVBs/exosomes (3). Virus RNA is translated into viral replicas polyproteins pp1a and 1ab, which are then cleaved into viral components by viral proteinases. Viral proteins and RNA are subsequently assembled into virions in the endoplasmic reticulum and Golgi (4 and 5) and then released out of the cell via exocytosis or directed into exosomes (6). Upon entry, COVID-19 virus may be directed into the exosomal pathway, and its component is sorted into exosomes for secretion and spreading (steps 3 and 6). Extracellular vesicles (exosomes and microvesicles) may contribute to spread this virus as they transfer such receptors as CD9 and ACE2, which make recipient cells susceptible for virus docking. ACE2, angiotensin-converting enzyme 2; EE, early endosome; ER, endoplasmic reticulum; GA, Golgi apparatus; MVB, multivesicular body; N, nucleus.
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