Down-regulation of K+ channels by human parvovirus B19 capsid protein VP1

Ahmed, Musaab; Almilaji, Ahmad; Muñoz, Carlos; Elvira, Bernat; Shumilina, Ekaterina; Bock, C.‐Thomas; Kandolf, Reinhard; Läng, Florian

doi:10.1016/j.bbrc.2014.07.003

Cited by 7 publications

(4 citation statements)

References 49 publications

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“…Its B19 minor capsid protein VP1 has intrinsic phospholipase A2 activity, which can increase the activity of Ca 2+ release-activated Ca 2+ channel ( I CRAC ), which is normally responsible for capacitative, store-operated Ca 2+ entry by increasing I Ca (Lupescu et al, 2006 ). PLA2 activity of VP1 is thought to underlie downregulation of Na + /K + -ATPase and a number of K + channels (mediating I Kr and inward rectifying currents, I Kir ; Almilaji et al, 2013 ; Ahmed et al, 2014 , 2015 ).…”

Section: Host-mediated and Viral-induced Inflammation And Can Promotementioning

confidence: 99%

What Is the Arrhythmic Substrate in Viral Myocarditis? Insights from Clinical and Animal Studies

et al. 2016

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Sudden cardiac death (SCD) remains an unsolved problem in the twenty-first century. It is often due to rapid onset, ventricular arrhythmias caused by a number of different clinical conditions. A proportion of SCD patients have identifiable diseases such as cardiomyopathies, but for others, the causes are unknown. Viral myocarditis is becoming increasingly recognized as a contributor to unexplained mortality, and is thought to be a major cause of SCD in the first two decades of life. Myocardial inflammation, ion channel dysfunction, electrophysiological, and structural remodeling may play important roles in generating life-threatening arrhythmias. The aim of this review article is to examine the electrophysiology of action potential conduction and repolarization and the mechanisms by which their derangements lead to triggered and reentrant arrhythmogenesis. By synthesizing experimental evidence from pre-clinical and clinical studies, a framework of how host (inflammation), and viral (altered cellular signaling) factors can induce ion electrophysiological and structural remodeling is illustrated. Current pharmacological options are mainly supportive, which may be accompanied by mechanical circulatory support. Heart transplantation is the only curative option in the worst case scenario. Future strategies for the management of viral myocarditis are discussed.

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Section: Host-mediated and Viral-induced Inflammation And Can Promotementioning

confidence: 99%

What Is the Arrhythmic Substrate in Viral Myocarditis? Insights from Clinical and Animal Studies

et al. 2016

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“…Secondly, PLA2-like activity of VP1 upregulates the activity of epithelial Na + channel ENaC which results in early swelling and later stiffening of the vascular endothelium [197]. Thirdly, downregulation of potassium channels such as Kv1.3, Kv1.5, Kir2.1 channels and inhibition of the Na + /K + -ATPase activity by VP1 leads to cell swelling and thus contributes to endothelial dysfunction [198,199]. PLA2 also appears to be relevant for efficient transfer of the viral genome from lysosomes and endosomes into the nucleus for viral replication [200].…”

Section: Pvb19mentioning

confidence: 99%

Virus-Host Interactions of Enteroviruses and Parvovirus B19 in Myocarditis

Peischard

Strutz‐Seebohm

et al. 2021

Cell Physiol Biochem

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Viral diseases are a major threat to modern society and the global health system. It is therefore of utter relevance to understand the way viruses affect the host as a basis to find new treatment solutions. The understanding of viral myocarditis (VMC) is incomplete and effective treatment options are lacking. This review will discuss the mechanism, effects, and treatment options of the most frequent myocarditis-causing viruses namely enteroviruses such as Coxsackievirus B3 (CVB3) and Parvovirus B19 (PVB19) on the human heart. Thereby, we focus on: 1. Viral entry: CVB3 use Coxsackievirus-Adenovirus-Receptor (CAR) and Decay Accelerating Factor (DAF) to enter cardiac myocytes while PVB19 use the receptor globoside (Gb4) to enter cardiac endothelial cells. 2. Immune system responses: The innate immune system mediated by activated cardiac toll-like receptors (TLRs) worsen inflammation in CVB3-infected mouse hearts. Different types of cells of the adaptive immune system are recruited to the site of inflammation that have either protective or adverse effects during VMC. 3. Autophagy: CVB3 evades autophagosomal degradation and misuses the autophasomal pathway for viral replication and release. 4. Viral replication sites: CVB3 promotes the formation of double membrane vesicles (DMVs), which it uses as replication sites. PVB19 uses the host cell nucleus as the replication site and uses the host cell DNA replication system. 5. Cell cycle manipulation: CVB3 attenuates the cell cycle at the G1/S phase, which promotes viral transcription and replication. PVB19 exerts cell cycle arrest in the S phase using its viral endonuclease activity. 6. Regulation of apoptosis: Enteroviruses prevent apoptosis during early stages of infection and promote cell death during later stages by using the viral proteases 2A and 3C, and viroporin 2B. PVB19 promotes apoptosis using the non-structural proteins NS1 and the 11 kDa protein. 7. Energy metabolism: Dysregulation of respiratory chain complex expression, activity and ROS production may be altered in CVB3- and PVB19-mediated myocarditis. 8. Ion channel modulation: CVB3-expression was indicated to alter calcium and potassium currents in Xenopus laevis oocytes and rodent cardiomyocytes. The phospholipase 2-like activity of PVB19 may alter several calcium, potassium and sodium channels. By understanding the general pathophysiological mechanisms of well-studied myocarditis-linked viruses, we might be provided with a guideline to handle other less-studied human viruses.

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“…Interestingly, MMP23 is highly expressed in some subtypes of lymphocytes, such as the NK (natural killer) cells [74]. Finally, components of some viruses, such as the capsid protein VP1 of Parvovirus B19, downregulate Kv1.3, as well as other ion channels [75].…”

Section: Tablementioning

confidence: 99%