ACE2‐enriched extracellular vesicles enhance infectivity of live SARS‐CoV‐2 virus

Tey, Sze Keong; Lam, Hoiyan; Wong, Samuel S. Y.; Zhao, Hanjun; To, Kelvin Kai-Wang; Yam, Judy Wai Ping

doi:10.1002/jev2.12231

Cited by 15 publications

(13 citation statements)

References 58 publications

(60 reference statements)

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“…Alternative strategies based on the biological methods, that is, applying neutralizing antibodies for viral inactivation of the EV and virion isolates, or purifying EVs from the isolates containing viruses by antibody capture beads, or a combination of both, warrant further investigations. Second, EVs from specific cell sources may modulate SARS‐CoV‐2 infectivity, for example, MSCs (Chutipongtanate et al., 2022 ) and ACE2‐expressing cells (Cocozza et al., 2020 ; El‐Shennawy et al., 2022 ; Tey et al., 2022 ). Calu‐3 cells used in this study are known to express surface ACE2 (Puray‐Chavez et al., 2021 ).…”

Section: Discussionmentioning

confidence: 99%

“…Calu‐3 cells used in this study are known to express surface ACE2 (Puray‐Chavez et al., 2021 ). Thus, ACE2‐expressing EVs derived from Calu‐3 cells may prevent SARS‐CoV‐2 infection via ACE2‐spike interaction (Cocozza et al., 2020 ; El‐Shennawy et al., 2022 ), or vice versa, these ACE2‐expressing EVs may facilitate the entry of SARS‐CoV‐2 into host cells through cellular EV uptake mechanisms (Tey et al., 2022 ). The dilemma of ACE2‐expressing respiratory epithelial cells as the host cell target, and the mechanisms to modulate SARS‐CoV‐2 infectivity via released ACE2‐expressing EVs, should be investigated in future studies.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Comparison of viral inactivation methods on the characteristics of extracellular vesicles from SARS‐CoV‐2 infected human lung epithelial cells

Kongsomros

Pongsakul

Panachan

et al. 2022

J of Extracellular Vesicle

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The interaction of SARS‐CoV‐2 infection with extracellular vesicles (EVs) is of particular interest at the moment. Studying SARS‐CoV‐2 contaminated‐EV isolates in instruments located outside of the biosafety level‐3 (BSL‐3) environment requires knowing how viral inactivation methods affect the structure and function of extracellular vesicles (EVs). Therefore, three common viral inactivation methods, ultraviolet‐C (UVC; 1350 mJ/cm 2 ), β‐propiolactone (BPL; 0.005%), heat (56°C, 45 min) were performed on defined EV particles and their proteins, RNAs, and function. Small EVs were isolated from the supernatant of SARS‐CoV‐2‐infected human lung epithelial Calu‐3 cells by stepwise centrifugation, ultrafiltration and qEV size‐exclusion chromatography. The EV isolates contained SARS‐CoV‐2. UVC, BPL and heat completely abolished SARS‐CoV‐2 infectivity of the contaminated EVs. Particle detection by electron microscopy and nanoparticle tracking was less affected by UVC and BPL than heat treatment. Western blot analysis of EV markers was not affected by any of these three methods. UVC reduced SARS‐CoV‐2 spike detectability by quantitative RT‐PCR and slightly altered EV‐derived β‐actin detection. Fibroblast migration‐wound healing activity of the SARS‐CoV‐2 contaminated‐EV isolate was only retained after UVC treatment. In conclusion, specific viral inactivation methods are compatible with specific measures in SARS‐CoV‐2 contaminated‐EV isolates. UVC treatment seems preferable for studying functions of EVs released from SARS‐CoV‐2 infected cells.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Comparison of viral inactivation methods on the characteristics of extracellular vesicles from SARS‐CoV‐2 infected human lung epithelial cells

Kongsomros

Pongsakul

Panachan

et al. 2022

J of Extracellular Vesicle

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“…Additionally, CD9 enhances lentiviral infection and improves transduction efficiency in immune-competent cells such as T lymphocytes and B cells [ 80 ]. In SARS-CoV-2 infection, EVs expressing ACE2 on their surface are suggested to be responsible for spreading and accelerating infection by assisting viral entry into cells [ 81 ]. EVs from the plasma of COVID-19 patients incorporate SARS-CoV-2 spike-derived fragments of proteins and RNA, albeit in a low copy number, but are able to progress the disease and induce immune responses [ 6 , 82 , 83 ].…”

Section: Roles Of Extracellular Vesicles In Covid-19 Pathogenesismentioning

confidence: 99%

Update on Extracellular Vesicle-Based Vaccines and Therapeutics to Combat COVID-19

Mustajab

Kwamboka

Choi

et al. 2022

IJMS

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The COVID-19 pandemic has had a deep impact on people worldwide since late 2019 when SARS-CoV-2 was first identified in Wuhan, China. In addition to its effect on public health, it has affected humans in various aspects of life, including social, economic, cultural, and political. It is also true that researchers have made vigorous efforts to overcome COVID-19 throughout the world, but they still have a long way to go. Accordingly, innumerable therapeutics and vaccine candidates have been studied for their efficacies and have been tried clinically in a very short span of time. For example, the versatility of extracellular vesicles, which are membrane-bound particles released from all types of cells, have recently been highlighted in terms of their effectiveness, biocompatibility, and safety in the fight against COVID-19. Thus, here, we tried to explain the use of extracellular vesicles as therapeutics and for the development of vaccines against COVID-19. Along with the mechanisms and a comprehensive background of their application in trapping the coronavirus or controlling the cytokine storm, we also discuss the obstacles to the clinical use of extracellular vesicles and how these could be resolved in the future.

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“…Recent studies have found some evidence that EVs bound to SARS-CoV-2 may promote SARS-CoV-2 infection of cells. Tey et al discovered that EVs derived from HEK293T cells enriched with ACE2 could dose-dependently promote SARS-CoV-2 infection of cells, which may be related to the easier uptake of EVs by cells (Tey et al, 2022). When the degradation of EVs and the channel of EVs are uptake by cells was blocked with bafilomycin A1 (BafA1) (which neutralizes lysosomal acidification) or cytochalasin D (a cytoskeleton inhibitor), this facilitation from ACE2-rich EVs was significantly reduced, but the precise mechanism is unknown.…”

Section: Evs As Accomplices In Promoting Sars-cov-2 Infectionmentioning

confidence: 99%

“…( 1) When SARS-CoV-2 enters the cell microenvironment, EVs that carry angiotensin-converting enzyme 2 (ACE2) as nanodecoys may prevent or assist virus colonization and entry (Berry et al, 2022;Cocozza et al, 2020;El-Shennawy et al, 2022), (2) When infection occurs, EVs obtained by in vitro cultivation of immune cells, mesenchymal stem cells, and other cells may be used to guard against intracellular replication, spread of the virus, and act as cytokine decoys (Chutipongtanate et al, 2022;Elashiry et al, 2021;Wang et al, 2022a). Meanwhile, EVs may also become prisoners of SARS-CoV-2, which may play immunomodulatory effects or aid in the spread of infection (Hassanpour et al, 2020;Ning et al, 2021;Pesce et al, 2022;Tey et al, 2022), (3) EVs obtained from mesenchymal stem cells in vitro are expected to help recover from COVID-19 related damage (Dinh et al, 2020;O'Driscoll, 2020;Sengupta et al 2020a;Zhu et al, 2022) and (4) Circulating EVs are also potentially involved in the acquired immune response against SARS-CoV-2 (Barberis et al, 2021). These potential results still contain a lot of unknowns and uncertainties, but we can gain some inspiration from these processes for the diagnoses, therapy, and prevention of COVID-19.…”

Section: Introductionmentioning

confidence: 99%

Meet changes with constancy: Defence, antagonism, recovery, and immunity roles of extracellular vesicles in confronting SARS‐CoV‐2

Chen

Song

et al. 2022

J of Extracellular Vesicle

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Coronavirus disease 2019 (COVID‐19), caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), has wrought havoc on the world economy and people's daily lives. The inability to comprehensively control COVID‐19 is due to the difficulty of early and timely diagnosis, the lack of effective therapeutic drugs, and the limited effectiveness of vaccines. The body contains billions of extracellular vesicles (EVs), which have shown remarkable potential in disease diagnosis, drug development, and vaccine carriers. Recently, increasing evidence has indicated that EVs may participate or assist the body in defence, antagonism, recovery and acquired immunity against SARS‐CoV‐2. On the one hand, intercepting and decrypting the general intelligence carried in circulating EVs from COVID‐19 patients will provide an important hint for diagnosis and treatment; on the other hand, engineered EVs modified by gene editing in the laboratory will amplify the effectiveness of inhibiting infection, replication and destruction of ever‐mutating SARS‐CoV‐2, facilitating tissue repair and making a better vaccine. To comprehensively understand the interaction between EVs and SARS‐CoV‐2, providing new insights to overcome some difficulties in the diagnosis, prevention and treatment of COVID‐19, we conducted a rounded review in this area. We also explain numerous critical challenges that these tactics face before they enter the clinic, and this work will provide previous ‘meet change with constancy’ lessons for responding to future similar public health disasters. Extracellular vesicles (EVs) provide a ‘meet changes with constancy’ strategy to combat SARS‐CoV‐2 that spans defence, antagonism, recovery, and acquired immunity. Targets for COVID‐19 diagnosis, therapy, and prevention of progression may be found by capture of the message decoding in circulating EVs. Engineered and biomimetic EVs can boost effects of the natural EVs, especially anti‐SARS‐CoV‐2, targeted repair of damaged tissue, and improvement of vaccine efficacy.

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ACE2‐enriched extracellular vesicles enhance infectivity of live SARS‐CoV‐2 virus

Cited by 15 publications

References 58 publications

Comparison of viral inactivation methods on the characteristics of extracellular vesicles from SARS‐CoV‐2 infected human lung epithelial cells

Comparison of viral inactivation methods on the characteristics of extracellular vesicles from SARS‐CoV‐2 infected human lung epithelial cells

Update on Extracellular Vesicle-Based Vaccines and Therapeutics to Combat COVID-19

Meet changes with constancy: Defence, antagonism, recovery, and immunity roles of extracellular vesicles in confronting SARS‐CoV‐2

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