Racemization Hypothesis of COVID-19. Tip of the Iceberg

2020 ◽  
Keyword(s):  
Phase Transitions ◽  
Host Cell ◽  
Viral Infections ◽  
Proteolytic Enzymes ◽  
Viral Proteins ◽  
Cell Interaction ◽  
Cell Physiology ◽  
Viral Glycoprotein ◽  
Host Interaction ◽  
The Impact

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.

Racemization Hypothesis of COVID-19. Tip of the Iceberg

2020 ◽  
Keyword(s):  
Phase Transitions ◽  
Host Cell ◽  
Viral Infections ◽  
Proteolytic Enzymes ◽  
Viral Proteins ◽  
Cell Interaction ◽  
Cell Physiology ◽  
Viral Glycoprotein ◽  
Host Interaction ◽  
The Impact

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.

scholarly journals Perturbation of host autophagy by the Irish potato famine pathogen

2014 ◽  
Vol 70 (a1) ◽  
pp. C826-C826
Author(s):  
Abbas Maqbool ◽  
Richard Richard ◽  
Tolga Bozkurt ◽  
Yasin Dagdas ◽  
Khaoula Belhai ◽  
...  
Keyword(s):  
Host Cell ◽  
Plant Cells ◽  
Irish Potato ◽  
Effector Proteins ◽  
Host Cells ◽  
Cell Physiology ◽  
Biochemical Basis ◽  
The Impact ◽  
Potato Famine ◽  
Irish Potato Famine

Autophagy is a catabolic process involving degradation of dysfunctional cytoplasmic components to ensure cellular survival under starvation conditions. The process involves formation of double-membrane vesicles called autophagosomes and delivery of the inner constituents to lytic compartments. It can also target invading pathogens, such as intracellular bacteria, for destruction and is thus implicated in innate immune pathways [1]. In response, certain mammalian pathogens deliver effector proteins into host cells that inhibit autophagy and contribute to enabling parasitic infection [2]. Pyhtophthora infestans, the Irish potato famine pathogen, is a causative agent of late blight disease in potato and tomato crops. It delivers a plethora of modular effector proteins into plant cells to promote infection. Once inside the cell, RXLR-type effector proteins engage with host cell proteins, to manipulate host cell physiology for the benefit of the pathogen. As plants lack an adaptive immune system, this provides a robust mechanism for pathogens to circumvent host defense. PexRD54 is an intracellular RXLR-type effector protein produced by P. infestans. PexRD54 interacts with potato homologues of autophagy protein ATG8 in plant cells. We have been investigating the structural and biochemical basis of the PexRD54/ATG8 interaction in vitro. We have purified PexRD54 and ATG8 independently and in complex from E. coli. Using protein/protein interaction studies we have shown that PexRD54 binds ATG8 with sub-micromolar affinity. We have also determined the structure of PexRD54 in the presence of ATG8. This crystal structure provides key insights into how the previously reported WY-fold of oomycete RXLR-type effectors [3] can be organized in multiple repeats. The structural data also provides insights into the interaction between PexRD54 and ATG8, suggesting further experiments to understand the impact of this interaction on host cell physiology and how this benefits the pathogen.

scholarly journals The Regulation of Flavivirus Infection by Hijacking Exosome-Mediated Cell–Cell Communication: New Insights on Virus–Host Interactions

Viruses ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 765
Author(s):  
José Manuel Reyes-Ruiz ◽  
Juan Fidel Osuna-Ramos ◽  
Luis Adrián De Jesús-González ◽  
Selvin Noé Palacios-Rápalo ◽  
Carlos Daniel Cordero-Rivera ◽  
...  
Keyword(s):  
Viral Infections ◽  
Cell Communication ◽  
Cell Interaction ◽  
Host Cells ◽  
Human Pathogens ◽  
Cellular Functions ◽  
Cellular Targets ◽  
Host Interaction ◽  
Flavivirus Infection

The arthropod-borne flaviviruses are important human pathogens, and a deeper understanding of the virus–host cell interaction is required to identify cellular targets that can be used as therapeutic candidates. It is well reported that the flaviviruses hijack several cellular functions, such as exosome-mediated cell communication during infection, which is modulated by the delivery of the exosomal cargo of pro- or antiviral molecules to the receiving host cells. Therefore, to study the role of exosomes during flavivirus infections is essential, not only to understand its relevance in virus–host interaction, but also to identify molecular factors that may contribute to the development of new strategies to block these viral infections. This review explores the implications of exosomes in flavivirus dissemination and transmission from the vector to human host cells, as well as their involvement in the host immune response. The hypothesis about exosomes as a transplacental infection route of ZIKV and the paradox effect or the dual role of exosomes released during flavivirus infection are also discussed here. Although several studies have been performed in order to identify and characterize cellular and viral molecules released in exosomes, it is not clear how all of these components participate in viral pathogenesis. Further studies will determine the balance between protective and harmful exosomes secreted by flavivirus infected cells, the characteristics and components that distinguish them both, and how they could be a factor that determines the infection outcome.

scholarly journals Vaccinia Virus B1R Kinase Interacts with JIP1 and Modulates c-Jun-Dependent Signaling

2006 ◽  
Vol 80 (15) ◽  
pp. 7667-7675 ◽  
Author(s):  
Claudio R. Santos ◽  
Sandra Blanco ◽  
Ana Sevilla ◽  
Pedro A. Lazo
Keyword(s):  
Vaccinia Virus ◽  
Host Cell ◽  
Kinase Activity ◽  
Viral Proteins ◽  
Cell Interaction ◽  
Scaffold Proteins ◽  
Mitogen Activated Protein Kinase ◽  
Potential Contribution ◽  
Mitogen Activated Protein ◽  
Host Cell Interaction

ABSTRACT Viruses have to adjust to the host cell to guarantee their life cycle and survival. This aspect of the virus-host cell interaction is probably performed by viral proteins, such as serine-threonine kinases, that are present early during infection. Vaccinia virus has an early Ser-Thr kinase, B1R, which, although required for successful viral infection, is poorly characterized regarding its effects on cellular proteins, and thus, its potential contribution to pathogenesis is not known. Signaling by mitogen-activated protein kinase (MAPK) is mediated by the assembly of complexes between these kinases and the JIP scaffold proteins. To understand how vaccinia virus B1R can affect the host, its roles in the cellular signaling by MAPK complexes and c-Jun activation have been studied. Independently of its kinase activity, B1R can interact with the central region of the JIP1 scaffold protein. The B1R-JIP1 complex increases the amount of MAPK bound to JIP1; thus, MKK7 and TAK1 either bind with higher affinity or bind more stably to JIP1, while there is an increase in the phosphorylation state of JNK bound to JIP1. The functional consequence of these more stable interactions is an increase in the activity of transcription factors, such as c-Jun, that respond to these complexes. Furthermore, B1R is also able to directly phosphorylate c-Jun in residues different from those targeted by JNK and, thus, B1R can also cooperate by an independent route in c-Jun activation. Vaccinia virus B1R can thus modulate the signaling of pathways that respond to cellular stress.

scholarly journals Interrelationships of Interferon and Immunity During Viral Infections

1970 ◽  
Vol 56 (1) ◽  
pp. 212-226 ◽  
Author(s):  
Lowell A. Glasgow
Keyword(s):  
Immune Responses ◽  
Vaccinia Virus ◽  
Host Resistance ◽  
Host Response ◽  
Viral Infections ◽  
Cell Interaction ◽  
Relative Importance ◽  
Host Interaction ◽  
Interferon Responses

Interferon is one determinant of host resistance. The immune responses, cellular or humoral, are other components. Cell-mediated responses appear to be involved in host resistance to certain viral infections, particularly the herpesvirus group and vaccinia virus. It is suggested that immune and interferon responses may complement one another and contribute to host resistance. The relative importance of each component depends upon the virus-host interaction. Finally, evidence has been presented which suggests that production of interferon as a result of antigen-sensitized cell interaction may further link these two components of the host response.

scholarly journals Global analysis of HBV-mediated host proteome and ubiquitylome change in HepG2.2.15 human hepatoblastoma cell line

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Sen Yuan ◽  
Yousaf Tanzeel ◽  
Xuezhang Tian ◽  
Dandan Zheng ◽  
Naz Wajeeha ◽  
...  
Keyword(s):  
Cell Culture ◽  
Host Cell ◽  
Cell Line ◽  
Hepg2 Cell ◽  
Isotope Labeling ◽  
Global Analysis ◽  
Cell Physiology ◽  
Host Proteins ◽  
Dane Particles ◽  
The Impact

AbstractHepatitis B virus (HBV) infection remains a major health issue worldwide and the leading cause of cirrhosis and hepatocellular carcinoma (HCC). It has been reported previously that HBV invasion can extensively alter transcriptome, the proteome of exosomes and host cell lipid rafts. The impact of HBV on host proteins through regulating their global post-translational modifications (PTMs), however, is not well studied. Viruses have been reported to exploit cellular processes by enhancing or inhibiting the ubiquitination of specific substrates. Nevertheless, host cell physiology in terms of global proteome and ubiquitylome has not been addressed yet. Here by using HBV-integrated HepG2.2.15 model cell line we first report that HBV significantly modify the host global ubiquitylome. As currently the most widely used HBV cell culture model, HepG2.2.15 can be cultivated for multiple generations for protein labeling, and can replicate HBV, express HBV proteins and secrete complete HBV Dane particles, which makes it a suitable cell line for ubiquitylome analysis to study HBV replication, hepatocyte immune response and HBV-related HCC progression. Our previous experimental results showed that the total ubiquitination level of HepG2.2.15 cell line was significantly higher than that of the corresponding parental HepG2 cell line. By performing a Ubiscan quantification analysis based on stable isotope labeling of amino acids in cell culture (SILAC) of HepG2.2.15 and HepG2 cell lines, we identified a total of 7188 proteins and the protein levels of nearly 19% of them were changed over 2-folds. We further identified 3798 ubiquitinated Lys sites in 1476 host proteins with altered ubiquitination in response to HBV. Our results also showed that the global proteome and ubiquitylome were negatively correlated, indicating that ubiquitination might be involved in the degradation of host proteins upon HBV integration. We first demonstrated the ubiquitination change of VAMP3, VAMP8, DNAJB6, RAB8A, LYN, VDAC2, OTULIN, SLC1A4, SLC1A5, HGS and TOLLIP. In addition, we described 5 novel host factors SLC1A4, SLC1A5, EIF4A1, TOLLIP and BRCC36 that efficiently reduced the amounts of secreted HBsAg and HBeAg. Overall, the HBV-mediated host proteome and ubiquitylome change we reported will provide a valuable resource for further investigation of HBV pathogenesis and host-virus interaction networks.

scholarly journals Uncovering potential host proteins and pathways that may interact with eukaryotic short linear motifs in viral proteins of MERS, SARS and SARS2 coronaviruses that infect humans

PLoS ONE ◽  
2021 ◽  
Vol 16 (2) ◽  
pp. e0246150
Author(s):  
Chu-Wen Yang ◽  
Zhi-Ling Shi
Keyword(s):  
Host Cell ◽  
Virus Replication ◽  
Viral Infections ◽  
Viral Proteins ◽  
Host Cells ◽  
Host Proteins ◽  
Cell Components ◽  
Linear Motifs ◽  
Novel Coronavirus ◽  
High Possibility

A coronavirus pandemic caused by a novel coronavirus (SARS-CoV-2) has spread rapidly worldwide since December 2019. Improved understanding and new strategies to cope with novel coronaviruses are urgently needed. Viruses (especially RNA viruses) encode a limited number and size (length of polypeptide chain) of viral proteins and must interact with the host cell components to control (hijack) the host cell machinery. To achieve this goal, the extensive mimicry of SLiMs in host proteins provides an effective strategy. However, little is known regarding SLiMs in coronavirus proteins and their potential targets in host cells. The objective of this study is to uncover SLiMs in coronavirus proteins that are present within host cells. These SLiMs have a high possibility of interacting with host intracellular proteins and hijacking the host cell machinery for virus replication and dissemination. In total, 1,479 SLiM hits were identified in the 16 proteins of 590 coronaviruses infecting humans. Overall, 106 host proteins were identified that may interact with SLiMs in 16 coronavirus proteins. These SLiM-interacting proteins are composed of many intracellular key regulators, such as receptors, transcription factors and kinases, and may have important contributions to virus replication, immune evasion and viral pathogenesis. A total of 209 pathways containing proteins that may interact with SLiMs in coronavirus proteins were identified. This study uncovers potential mechanisms by which coronaviruses hijack the host cell machinery. These results provide potential therapeutic targets for viral infections.

scholarly journals Extracellular vesicles released by the human gut symbiont Bacteroides thetaiotaomicron in the mouse intestine are enriched in a selected range of proteins that influence host cell physiology and metabolism

2020 ◽  
Author(s):  
Regis Stentz ◽  
Udo Wegmann ◽  
Maria Guirro ◽  
Will Bryant ◽  
Avani Ranjit ◽  
...  
Keyword(s):  
Host Cell ◽  
Extracellular Vesicles ◽  
Cell Function ◽  
Bile Salt Hydrolase ◽  
Cell Physiology ◽  
Bacteroides Thetaiotaomicron ◽  
Human Gut ◽  
The Impact

Abstract It is becoming increasingly clear that bacterial extracellular vesicles (BEVs) produced by members of the intestinal microbiota can contribute to microbe-host cell interactions that impact on host health. A major unresolved question is the nature of the cargo packaged into these BEVs and how they can impact on host cell function. Here we have analysed the proteome of BEVs produced by the major human gut symbiont Bacteroides thetaiotaomicron in both in vitro cultures using defined and complex medias, and in vivo in fed or fasted animals to determine the impact of nutrient stress on the BEV proteome, and to identify proteins specifically enriched in BEVs produced in vivo. In contrast to BEVs produced in vitro where limiting nutrient provision resulted in an increase in a large fraction of proteins, the protein content of BEVs extracted from fasted versus fed mice was less affected with similar numbers of proteins showing increased and decreased abundance. We identified 102 proteins exclusively enriched in BEVs in vivo of which the majority (66/102) were enriched independently of their expression in the parent cells implicating the existence of an active mechanism to drive the selection of a group of proteins for their secretion into BEVs within the intestine. Amongst these abundantly expressed proteins in BEVs in vivo were a bile salt hydrolase and a dipeptidyl peptidase IV that were characterised further and shown to be active and able to degrade host-derived substrates with defined roles in metabolism. Collectively these findings provide additional evidence for the role of BEVs in microbiota-host interactions with their contents playing key roles in the maintenance of intestinal homeostasis, and host metabolism.

scholarly journals The genes to Covid-19 suceptibility

ANALES RANM ◽  
2020 ◽  
Vol 137 (137(02)) ◽  
pp. 117-120
Author(s):  
Antonio López Farré
Keyword(s):  
Host Cell ◽  
Genetic Polymorphisms ◽  
Viral Infections ◽  
Cell Interaction ◽  
Coagulation System ◽  
Single Nucleotide ◽  
Infected People ◽  
Genes Encoding ◽  
Infection Resistance ◽  
Host Cell Interaction

COVID-19 is affecting people in very different ways. Among this variability in the susceptibility to COVID-19 some infected people will remain non-symptomatically affected or if they have symptoms, these will be very slight. In other viral infections, the existence of genetic polymorphisms that modify the susceptibility to viral infection and its symptoms has been demonstrated. In the case of COVID-19, genetic polymorphisms have also been identified in different proteins related to the interaction and internament of COVID-19 in the host cell. These genetic polymorphisms identified as single nucleotide polymorphism in genes encoding proteins such as ACE1, ACE2, CD140 or TMPRS have already been associated with greater ease of the virus to infect the cell, but also for infection resistance. It is evident that, the genetic variability of the proteins related to the COVIDS-19-host cell interaction is important, however, it could be also important the existence of genetic polymorphisms located in genes related to the pathological consequences promoted by COVID-19 infection, such as genes related to the thrombo-coagulation system or the inflammatory response. In addition, the influence of other factors including life-style, physical exercise but also co-morbidities may modely genetic-mediated COVID-19 infection.

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