Mitochondrial Interactome: A Focus on Antiviral Signaling Pathways

Refolo, Giulia; Vescovo, Tiziana; Piacentini, Mauro; Fimia, Gian María; Ciccosanti, Fabiola

doi:10.3389/fcell.2020.00008

Cited by 98 publications

(86 citation statements)

References 144 publications

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“…Our previous work established that platelets could release mitochondria contributing to the immune modulation and islet b-cell regeneration [13]. To explore the mitochondrial function in viral infection, flow cytometry indicated that while the purified platelet-derived mitochondria did not express ACE2 (Figures 3D), they strongly display the mitochondrial antiviral-signaling protein (MAVS) with the percentage of MitoTracker Red + HSP60 + MAVS + mitochondria at 96.02% ± 2.74% ( Figure 3E, n = 3) [21]. This data suggests that platelets may have potential to improve antiviral immunity through the releasing mitochondria.…”

Section: No Expression Of Ace2 On Plateletsmentioning

confidence: 99%

High expression of angiotensin-converting enzyme-2 (ACE2) on tissue macrophages that may be targeted by virus SARS-CoV-2 in COVID-19 patients

Song

et al. 2020

Preprint

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Angiotensin-converting enzyme-2 (ACE2) has been recognized as the binding receptor for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that infects host cells, causing the development of the new coronavirus infectious disease (COVID-19). To better understand the pathogenesis of COVID-19 and build up the host anti-viral immunity, we examined the levels of ACE2 expression on different types of immune cells including tissue macrophages. Flow cytometry demonstrated that there was little to no expression of ACE2 on most of the human peripheral blood-derived immune cells including CD4+ T, CD8+ T, activated CD4+ T, activated CD8+ T, CD4+CD25+CD127low/- regulatory T cells (Tregs), Th17 cells, NKT cells, B cells, NK cells, monocytes, dendritic cells (DCs), and granulocytes. Additionally, there was no ACE2 expression (< 1%) found on platelets. Compared with interleukin-4-treated type 2 macrophages (M2), the ACE2 expression was markedly increased on the activated type 1 macrophages (M1) after the stimulation with lipopolysaccharide (LPS). Immunohistochemistry demonstrated that high expressions of ACE2 were colocalized with tissue macrophages, such as alveolar macrophages found within the lungs and Kupffer cells within livers of mice. Flow cytometry confirmed the very low level of ACE2 expression on human primary pulmonary alveolar epithelial cells. These data indicate that alveolar macrophages, as the frontline immune cells, may be directly targeted by the SARS-CoV-2 infection and therefore need to be considered for the prevention and treatment of COVID-19.

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Section: No Expression Of Ace2 On Plateletsmentioning

confidence: 99%

High expression of angiotensin-converting enzyme-2 (ACE2) on tissue macrophages that may be targeted by virus SARS-CoV-2 in COVID-19 patients

Song

et al. 2020

Preprint

View full text Add to dashboard Cite

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“…For example, mitochondria controls cell cycle ( Antico Arciuch et al, 2012 ), cellular differentiation ( Papa et al, 2019 ), signal transduction ( Bohovych and Khalimonchuk, 2016 ), cell metabolism ( Spinelli and Haigis, 2018 ), and apoptosis ( Wang and Youle, 2009 ). In addition, mitochondria serve as an anti-viral signaling platform by activating immune responses through MAVS (mitochondrial antiviral signaling) ( Seth et al, 2005 ; Jacobs and Coyne, 2013 ; Refolo et al, 2020 ) and initiating cell death ( Lei et al, 2009 ). It is therefore not surprising that viruses target mitochondria to promote viral replication ( Chatel-Chaix et al, 2016 ; Barbier et al, 2017 ).…”

Section: Introductionmentioning

confidence: 99%

Mitochondria Targeted Viral Replication and Survival Strategies—Prospective on SARS-CoV-2

et al. 2020

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SARS-CoV-2 is a positive sense RNA coronavirus that constitutes a new threat for the global community and economy. While vaccines against SARS-CoV-2 are being developed, the mechanisms through which this virus takes control of an infected cell to replicate remains poorly understood. Upon infection, viruses completely rely on host cell molecular machinery to survive and replicate. To escape from the immune response and proliferate, viruses strategically modulate cellular metabolism and alter subcellular organelle architecture and functions. One way they do this is by modulating the structure and function of mitochondria, a critical cellular metabolic hub but also a key platform for the regulation of cellular immunity. This versatile nature of mitochondria defends host cells from viruses through several mechanisms including cellular apoptosis, ROS signaling, MAVS activation and mitochondrial DNA-dependent immune activation. These events are regulated by mitochondrial dynamics, a process by which mitochondria alter their structure (including their length and connectivity) in response to stress or other cues. It is therefore not surprising that viruses, including coronaviruses hijack these processes for their survival. In this review, we highlight how positive sense RNA viruses modulate mitochondrial dynamics and metabolism to evade mitochondrial mediated immune response in order to proliferate.

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“…Some viral proteins have been shown to interact with MAVS proteins and dampen their activity. Viral proteases can also cleave MAVS ( 144 ). Recently, miR-22 was found to inhibit MAVS expression at the RNA level ( 145 ).…”

Section: Viral Manipulation Of Autophagy-dependent Regulation Of Innamentioning

confidence: 99%

Regulation of Innate Immune Responses by Autophagy: A Goldmine for Viruses

2020

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Autophagy is a lysosomal degradation pathway for intracellular components and is highly conserved across eukaryotes. This process is a key player in innate immunity and its activation has anti-microbial effects by directly targeting pathogens and also by regulating innate immune responses. Autophagy dysfunction is often associated with inflammatory diseases. Many studies have shown that it can also play a role in the control of innate immunity by preventing exacerbated inflammation and its harmful effects toward the host. The arms race between hosts and pathogens has led some viruses to evolve strategies that enable them to benefit from autophagy, either by directly hijacking the autophagy pathway for their life cycle, or by using its regulatory functions in innate immunity. The control of viral replication and spread involves the production of anti-viral cytokines. Controlling the signals that lead to production of these cytokines is a perfect way for viruses to escape from innate immune responses and establish successful infection. Published reports related to this last viral strategy have extensively grown in recent years. In this review we describe several links between autophagy and regulation of innate immune responses and we provide an overview of how viruses exploit these links for their own benefit.

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Mitochondrial Interactome: A Focus on Antiviral Signaling Pathways

Cited by 98 publications

References 144 publications

High expression of angiotensin-converting enzyme-2 (ACE2) on tissue macrophages that may be targeted by virus SARS-CoV-2 in COVID-19 patients

High expression of angiotensin-converting enzyme-2 (ACE2) on tissue macrophages that may be targeted by virus SARS-CoV-2 in COVID-19 patients

Mitochondria Targeted Viral Replication and Survival Strategies—Prospective on SARS-CoV-2

Regulation of Innate Immune Responses by Autophagy: A Goldmine for Viruses

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