Hepatitis C virus p7 induces mitochondrial depolarization of isolated liver mitochondria

You, Deok‑Gyun; Lee, Hye‐Ra; Kim, Won‐Ki; Kim, Hyung Jung; Lee, Gi Young; Yoo, Doo-Yeol

doi:10.3892/mmr.2017.7809

Cited by 5 publications

(3 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Furthermore, Ma et al demonstrated that the IVA M2 viroporin exhibits proton channel activity and induces ROS production required to antagonize autophagy and amplify the MAVS signaling pathway [ 91 ]. Lee et al, 2020, described that HCV has two viroporins: P7, which permeabilizes the mitochondrial membrane via interaction with phosphatidyl serine (a negatively charged phospholipid) located in the lipid rafts of membranes, and another HCV core viroporin, which is located in the outer mitochondrial membrane and decreases with an increase in ROS production [ 71 , 92 ].…”

Section: Mitochondrial Ros and Viroporinsmentioning

confidence: 99%

Viroporins Manipulate Cellular Powerhouses and Modulate Innate Immunity

Cedillo-Barrón,

García-Cordero,

Visoso-Carvajal

et al. 2024

Viruses

View full text Add to dashboard Cite

Viruses have a wide repertoire of molecular strategies that focus on their replication or the facilitation of different stages of the viral cycle. One of these strategies is mediated by the activity of viroporins, which are multifunctional viral proteins that, upon oligomerization, exhibit ion channel properties with mild ion selectivity. Viroporins facilitate multiple processes, such as the regulation of immune response and inflammasome activation through the induction of pore formation in various cell organelle membranes to facilitate the escape of ions and the alteration of intracellular homeostasis. Viroporins target diverse membranes (such as the cellular membrane), endoplasmic reticulum, and mitochondria. Cumulative data regarding the importance of mitochondria function in multiple processes, such as cellular metabolism, energy production, calcium homeostasis, apoptosis, and mitophagy, have been reported. The direct or indirect interaction of viroporins with mitochondria and how this interaction affects the functioning of mitochondrial cells in the innate immunity of host cells against viruses remains unclear. A better understanding of the viroporin–mitochondria interactions will provide insights into their role in affecting host immune signaling through the mitochondria. Thus, in this review, we mainly focus on descriptions of viroporins and studies that have provided insights into the role of viroporins in hijacked mitochondria.

show abstract

Section: Mitochondrial Ros and Viroporinsmentioning

confidence: 99%

Viroporins Manipulate Cellular Powerhouses and Modulate Innate Immunity

Cedillo-Barrón,

García-Cordero,

Visoso-Carvajal

et al. 2024

Viruses

View full text Add to dashboard Cite

show abstract

“…Delayed cleavage of E2-p7 is important for mature viral particle assembly [162]. HCV p7 also causes depolarisation of the mitochondrial membrane and mitochondrial acidification which promotes HCV particle production [163]. The key features of the p7 structure are conserved among HCV genotypes.…”

Section: P7 Structure and Functionmentioning

confidence: 99%

Unravelling the Immunomodulatory Effects of Viral Ion Channels, towards the Treatment of Disease

Gargan

Stevenson

2021

Viruses

View full text Add to dashboard Cite

The current COVID-19 pandemic has highlighted the need for the research community to develop a better understanding of viruses, in particular their modes of infection and replicative lifecycles, to aid in the development of novel vaccines and much needed anti-viral therapeutics. Several viruses express proteins capable of forming pores in host cellular membranes, termed “Viroporins”. They are a family of small hydrophobic proteins, with at least one amphipathic domain, which characteristically form oligomeric structures with central hydrophilic domains. Consequently, they can facilitate the transport of ions through the hydrophilic core. Viroporins localise to host membranes such as the endoplasmic reticulum and regulate ion homeostasis creating a favourable environment for viral infection. Viroporins also contribute to viral immune evasion via several mechanisms. Given that viroporins are often essential for virion assembly and egress, and as their structural features tend to be evolutionarily conserved, they are attractive targets for anti-viral therapeutics. This review discusses the current knowledge of several viroporins, namely Influenza A virus (IAV) M2, Human Immunodeficiency Virus (HIV)-1 Viral protein U (Vpu), Hepatitis C Virus (HCV) p7, Human Papillomavirus (HPV)-16 E5, Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) Open Reading Frame (ORF)3a and Polyomavirus agnoprotein. We highlight the intricate but broad immunomodulatory effects of these viroporins and discuss the current antiviral therapies that target them; continually highlighting the need for future investigations to focus on novel therapeutics in the treatment of existing and future emergent viruses.

show abstract

“…As expected, Gd 3+ ions significantly blocked the macroscopic currents triggered by p7 ( Figure 5A). Because p7 has been known to target the ER, mitochondria, and plasma membrane, and can cause mitochondrial depolarization in cells [12] and in purified mitochondria [19], we isolated mitochondria from mouse liver and applied Gd 3+ ions for 10 min, followed by staining with the ∆ψm indicator (JC-1) to examine the inhibitory effect on mitochondrial depolarization. We found that p7 induced mitochondrial depolarization, but Gd 3+ ions had no significant effect on the membrane potential of intact mitochondria.…”

Section: Gd 3+ Ions Block the Channel Activity Of P7 In The Bilayer Amentioning

confidence: 99%

Hepatitis C Virus p7 Induces Membrane Permeabilization by Interacting with Phosphatidylserine

Lee

You

et al. 2020

IJMS

Self Cite

View full text Add to dashboard Cite

Hepatitis C virus (HCV) p7 is known to be a nonselective cation channel for HCV maturation. Because the interaction of HCV proteins with host lipids in the endoplasmic reticulum membrane is crucial for the budding process, the identification of p7–lipid interactions could be important for understanding the HCV life cycle. Here, we report that p7 interacts with phosphatidylserine (PS) to induce membrane permeabilization. The interaction of p7 with PS was not inhibited by Gd3+ ions, which have been known to interact with negatively charged lipids, but channel activity and p7-induced mitochondrial depolarization were inhibited by Gd3+ ions. From the present results, we suggest that the p7–PS interaction plays an essential role in regulating its ion channel function and could be a potential molecular target for anti-HCV therapy.

show abstract

Hepatitis C virus p7 induces mitochondrial depolarization of isolated liver mitochondria

Cited by 5 publications

References 23 publications

Viroporins Manipulate Cellular Powerhouses and Modulate Innate Immunity

Viroporins Manipulate Cellular Powerhouses and Modulate Innate Immunity

Unravelling the Immunomodulatory Effects of Viral Ion Channels, towards the Treatment of Disease

Hepatitis C Virus p7 Induces Membrane Permeabilization by Interacting with Phosphatidylserine

Contact Info

Product

Resources

About