scholarly journals Dysregulation of host cell calcium signaling during viral infections: Emerging paradigm with high clinical relevance

2021 ◽  
pp. 101004
Author(s):  
Suman Saurav ◽  
Jyoti Tanwar ◽  
Kriti Ahuja ◽  
Rajender K. Motiani
2003 ◽  
Vol 278 (17) ◽  
pp. 15456
Author(s):  
Frank Ch. Mooren ◽  
Verena Hlouschek ◽  
Till Finkes ◽  
Stefan Turi ◽  
Ina Alexandra Weber ◽  
...  

2015 ◽  
Vol 2015 ◽  
pp. 1-12 ◽  
Author(s):  
Ingrid Lajdova ◽  
Viera Spustova ◽  
Adrian Oksa ◽  
Zuzana Kaderjakova ◽  
Dusan Chorvat ◽  
...  

Intracellular calcium concentration in peripheral blood mononuclear cells (PBMCs) of patients with chronic kidney disease (CKD) is significantly increased, and the regulatory mechanisms maintaining cellular calcium homeostasis are impaired. The purpose of this study was to examine the effect of vitaminD3on predominant regulatory mechanisms of cell calcium homeostasis. The study involved 16 CKD stages 2-3 patients with vitamin D deficiency treated with cholecalciferol 7000–14000 IU/week for 6 months. The regulatory mechanisms of calcium signaling were studied in PBMCs and red blood cells. After vitaminD3supplementation, serum concentration of 25(OH)D3increased (P<0.001) and[Ca2+]idecreased (P<0.001). The differences in[Ca2+]iwere inversely related to differences in 25(OH)D3concentration (P<0.01). VitaminD3supplementation decreased the calcium entry through calcium release activated calcium (CRAC) channels and purinergic P2X7channels. The function of P2X7receptors was changed in comparison with their baseline status, and the expression of these receptors was reduced. There was no effect of vitaminD3on P2X7pores and activity of plasma membrane Ca2+-ATPases. VitaminD3supplementation had a beneficial effect on[Ca2+]idecreasing calcium entry via CRAC and P2X7channels and reducing P2X7receptors expression.


FEBS Letters ◽  
2007 ◽  
Vol 581 (14) ◽  
pp. 2611-2615 ◽  
Author(s):  
Valéry Daubie ◽  
Robert De Decker ◽  
Charles Nicaise ◽  
Roland Pochet

Metabolites ◽  
2020 ◽  
Vol 10 (9) ◽  
pp. 356 ◽  
Author(s):  
David Balgoma ◽  
Luis Gil-de-Gómez ◽  
Olimpio Montero

The pathogenic mechanisms underlying the Biology and Biochemistry of viral infections are known to depend on the lipid metabolism of infected cells. From a lipidomics viewpoint, there are a variety of mechanisms involving virus infection that encompass virus entry, the disturbance of host cell lipid metabolism, and the role played by diverse lipids in regard to the infection effectiveness. All these aspects have currently been tackled separately as independent issues and focused on the function of proteins. Here, we review the role of cholesterol and other lipids in ssRNA+ infection.


The impact of viral infections on the central nervous system is widely known. Virus-related neuropsychiatric and neurobehavioral syndromes are caused by the distortion of cognitive, affective, behavioral, and perceptual domains. Although it is a commonly known phenomenon, the mechanism behind it is not well-understood. The contagious and deadly features of coronavirus disease 2019 (COVID-19) have been associated with the virus-host cell interaction at the molecular level. However, there is no reliable biomarker characterizing the disease progression. Studies of the structure, function, and evolution of coronavirus transmembrane spike glycoproteins (S-, N-, and E-proteins) suggest an essential role of protein chirality in virus-cell membrane interaction. The virus-host interaction is the subject of multidisciplinary research from the biochirality and systems biology, to cell physiology and non-equilibrium thermodynamics of phase transitions in proteins. At the protein level, virus-host interaction is modulated by the amino acid sequence of viral proteins and cellular metabolism. Enzymatic and spontaneous post-translational modifications (PTMs) are two mutually influential mechanisms governing the dynamics of virus and host cell proteome. Among them, phosphorylation and racemization are the most inter-related and studied. The spontaneous phase transitions within viral glycoprotein impacts the cell-entry capability of the virus. The spontaneous racemization is a particular and highly specific metabolic event in virus-cell interaction that is the focus of our attention. Many viral proteins are characterized by a high proportion of the serine (Ser) residues, which are the common target of the host-cell glycosylation, phosphorylation, and racemization, and proteolytic enzymes. Particularly, coronavirus N proteins were found to be phosphorylated at multiple Ser residues, a portion of which are shown to be phosphorylation-prone by the Ser-associated kinases. Since Ser is known as one of the most racemization prone amino acids, we promote an idea of the specific impact of spontaneous racemization at Ser residues on virus-host interaction.


2010 ◽  
Vol 9 (11) ◽  
pp. 1680-1689 ◽  
Author(s):  
Kristin R. Sweeney ◽  
Naomi S. Morrissette ◽  
Stephanie LaChapelle ◽  
Ira J. Blader

ABSTRACT Toxoplasma gondii is an obligate intracellular protozoan parasite that invades and replicates within most nucleated cells of warm-blooded animals. The basis for this wide host cell tropism is unknown but could be because parasites invade host cells using distinct pathways and/or repertoires of host factors. Using synchronized parasite invasion assays, we found that host microtubule disruption significantly reduces parasite invasion into host cells early after stimulating parasite invasion but not at later time points. Host microtubules are specifically associated with the moving junction, which is the site of contact between the host cell and the invading parasite. Host microtubules are specifically associated with the moving junction of those parasites invading early after stimulating invasion but not with those invading later. Disruption of host microtubules has no effect on parasite contact, attachment, motility, or rate of penetration. Rather, host microtubules hasten the time before parasites commence invasion. This effect on parasite invasion is distinct from the role that host microtubules play in bacterial and viral infections, where they function to traffic the pathogen or pathogen-derived material from the host cell's periphery to its interior. These data indicate that the host microtubule cytoskeleton is a structure used by Toxoplasma to rapidly infect its host cell and highlight a novel function for host microtubules in microbial pathogenesis.


2021 ◽  
Author(s):  
◽  
Scott Anthony Lawrence

<p>Coral reefs are in decline worldwide. Much of this decline is attributable to mass coral bleaching events and disease outbreaks, both of which are linked to anthropogenic climate change. Despite increased research effort, much remains unknown about these phenomena, especially the causative agents of many coral diseases. In particular, coral-associated viruses have received little attention, and their potential roles in coral diseases are largely unknown. This study aimed to address this lack of information by characterising the viruses associated with reef-building corals and Symbiodinium (dinoflagellates that can form symbioses with corals).  Symbiodinium virus screening experiments revealed the presence of numerous and varied virus-like particles (VLPs) inside cells. Of the 49 Symbiodinium cultures screened, approximately one third contained putative latent viral infections that could be induced to enter their lytic cycle by UV irradiation. Electron microscope examination revealed VLPs closely resembling viruses previously found in dinoflagellates and other microalgae. Three cultures that showed evidence of latent viral infections were chosen for whole transcriptome sequencing, which revealed the presence of viral genes that were expressed in several different types of Symbiodinium. The relationship between the detected genes and known viral gene sequences suggested that the cells were infected with double-stranded DNA (dsDNA) viruses.  In order to determine how the host cell responds to stress-induced viral infection, the expression levels of genes associated with stress response and viral infection were measured. The expression levels of many genes were unchanged following UV stress, and expression of genes that were predicted to be upregulated following stress, such as those encoding antioxidant enzymes, in fact showed lower expression levels. Despite this, several groups of genes involved in viral infection and host cell response were upregulated following stress, providing further evidence for stress-induced latent or chronic viral infections.  In addition to the research carried out on Symbiodinium cell cultures, viruses associated with three coral diseases were studied using electron microscopy. Virus-like particles were present in coral and Symbiodinium cells from all three diseases, but viral abundance was correlated with disease state in only one: white patch syndrome (WPS) of Porites australiensis. The locations and morphologies of the VLPs associated with WPS suggested the presence of dsDNA and single-stranded RNA (ssRNA) viruses infecting both the coral animal and Symbiodinium cells. DNA sequences obtained from WPS-affected corals matched closely with sequences obtained from VLP-containing Symbiodinium cells. Based on the evidence gathered from Symbiodinium cell cultures and coral tissues, I propose a theoretical model of viral infection in WPS. In this model, the coral animal cells are routinely subject to chronic viral infections, and Symbiodinium cells harbour two types of chronic or latent infections – a dsDNA and an ssRNA virus – that can be induced via stress, resulting in cell lysis or loss of the cells from the coral host.  In addition to detection and rudimentary identification of viruses infecting Symbiodinium cells, this study generated the largest dinoflagellate transcriptomic dataset to date. These data will prove valuable for future research into Symbiodinium, both in terms of viral infections and more generally.</p>


2021 ◽  
Author(s):  
Julia Y. Wang ◽  
Michael W. Roehrl ◽  
Victor B. Roehrl ◽  
Michael H. Roehrl

Chronic and debilitating autoimmune sequelae pose a grave concern for the post-COVID-19 pandemic era. Based on our discovery that the glycosaminoglycan dermatan sulfate (DS) displays peculiar affinity to apoptotic cells and autoantigens (autoAgs) and that DS-autoAg complexes cooperatively stimulate autoreactive B1 cell responses, we compiled a database of 751 candidate autoAgs from six human cell types. At least 657 of these have been found to be affected by SARS-CoV-2 infection based on currently available multi-omic COVID data, and at least 400 are confirmed targets of autoantibodies in a wide array of autoimmune diseases and cancer. The autoantigen-ome is significantly associated with various processes in viral infections, such as translation, protein processing, and vesicle transport. Interestingly, the coding genes of autoAgs predominantly contain multiple exons with many possible alternative splicing variants, short transcripts, and short UTR lengths. These observations and the finding that numerous autoAgs involved in RNA-splicing showed altered expression in viral infections suggest that viruses exploit alternative splicing to reprogram host cell machinery to ensure viral replication and survival. While each cell type gives rise to a unique pool of autoAgs, 39 common autoAgs associated with cell stress and apoptosis were identified from all six cell types, with several being known markers of systemic autoimmune diseases. In particular, the common autoAg UBA1 that catalyzes the first step in ubiquitination is encoded by an X-chromosome escape gene. Given its essential function in apoptotic cell clearance and that X-inactivation escape tends to increase with aging, UBA1 dysfunction can therefore predispose aging women to autoimmune disorders. In summary, we propose a model of how viral infections lead to extensive molecular alterations and host cell death, autoimmune responses facilitated by autoAg-DS complexes, and ultimately autoimmune diseases. Overall, this master autoantigen-ome provides a molecular guide for investigating the myriad of autoimmune sequalae to COVID-19 and clues to the rare but reported adverse effects of the currently available COVID vaccines.


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