scholarly journals SARS-CoV2 envelop proteins reshape the serological responses of COVID-19 patients

2021 ◽  
Author(s):  
Sophie Martin ◽  
Christopher Heslan ◽  
Gwénaële Jégou ◽  
Leif A. Eriksson ◽  
Matthieu Le Gallo ◽  
...  
Keyword(s):  
Viral Proteins ◽  
The Body ◽  
Membrane Insertion ◽  
Host Immune System ◽  
Topological Features ◽  
Viral Particles ◽  
M Proteins ◽  
Serological Status ◽  
Specific Igg ◽  
Humoral Responses

AbstractThe SARS-CoV-2 pandemic has elicited a unique international mobilization of the scientific community to better understand this coronavirus and its associated disease and to develop efficient tools to combat infection. Similar to other coronavirae, SARS-CoV-2 hijacks the host cell complex secretory machinery to produce properly folded viral proteins that will compose the nascent virions; including Spike, Envelope and Membrane proteins, the most exposed membrane viral proteins to the host immune system. Antibody response is part of the anti-viral immune arsenal that infected patients develop to fight viral particles in the body. Herein, we investigate the immunogenic potential of Spike (S), Envelope (E) and Membrane (M) proteins using a human cell-based system to mimic membrane insertion and N-glycosylation. We show that both S and M proteins elicit the production of specific IgG, IgM and IgA in SARS-CoV-2 infected patients. Elevated Ig responses were observed in COVID+ patients with moderate and severe forms of the disease. Finally, when SARS-CoV-2 Spike D614 and G614 variants were compared, reduced Ig binding was observed with the Spike G614 variant. Altogether, this study underlines the needs for including topological features in envelop proteins to better characterize the serological status of COVID+ patients, points towards an unexpected immune response against the M protein and shows that our assay could represent a powerful tool to test humoral responses against actively evolving SARS-CoV-2 variants and vaccine effectiveness.

scholarly journals SARS-CoV-2 Antigens Expressed in Plants Detect Antibody Responses in COVID-19 Patients

2021 ◽  
Vol 12 ◽  
Author(s):  
Mohau S. Makatsa ◽  
Marius B. Tincho ◽  
Jerome M. Wendoh ◽  
Sherazaan D. Ismail ◽  
Rofhiwa Nesamari ◽  
...  
Keyword(s):  
High Sensitivity ◽  
High Specificity ◽  
Viral Proteins ◽  
Antibody Responses ◽  
Robust Detection ◽  
Recombinant Plant ◽  
Specific Igg ◽  
African Patients ◽  
Global Threat ◽  
Humoral Responses

Background: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has swept the world and poses a significant global threat to lives and livelihoods, with 115 million confirmed cases and at least 2.5 million deaths from Coronavirus disease 2019 (COVID-19) in the first year of the pandemic. Developing tools to measure seroprevalence and understand protective immunity to SARS-CoV-2 is a priority. We aimed to develop a serological assay using plant-derived recombinant viral proteins, which represent important tools in less-resourced settings.Methods: We established an indirect ELISA using the S1 and receptor-binding domain (RBD) portions of the spike protein from SARS-CoV-2, expressed in Nicotiana benthamiana. We measured antibody responses in sera from South African patients (n = 77) who had tested positive by PCR for SARS-CoV-2. Samples were taken a median of 6 weeks after the diagnosis, and the majority of participants had mild and moderate COVID-19 disease. In addition, we tested the reactivity of pre-pandemic plasma (n = 58) and compared the performance of our in-house ELISA with a commercial assay. We also determined whether our assay could detect SARS-CoV-2-specific IgG and IgA in saliva.Results: We demonstrate that SARS-CoV-2-specific immunoglobulins are readily detectable using recombinant plant-derived viral proteins, in patients who tested positive for SARS-CoV-2 by PCR. Reactivity to S1 and RBD was detected in 51 (66%) and 48 (62%) of participants, respectively. Notably, we detected 100% of samples identified as having S1-specific antibodies by a validated, high sensitivity commercial ELISA, and optical density (OD) values were strongly and significantly correlated between the two assays. For the pre-pandemic plasma, 1/58 (1.7%) of samples were positive, indicating a high specificity for SARS-CoV-2 in our ELISA. SARS-CoV-2-specific IgG correlated significantly with IgA and IgM responses. Endpoint titers of S1- and RBD-specific immunoglobulins ranged from 1:50 to 1:3,200. S1-specific IgG and IgA were found in saliva samples from convalescent volunteers.Conclusion: We demonstrate that recombinant SARS-CoV-2 proteins produced in plants enable robust detection of SARS-CoV-2 humoral responses. This assay can be used for seroepidemiological studies and to measure the strength and durability of antibody responses to SARS-CoV-2 in infected patients in our setting.

scholarly journals Mimicry between respiratory virus proteins and some human immune proteins

2020 ◽  
Vol 10 (2) ◽  
pp. 305-314
Author(s):  
I. N. Zhilinskaya
Keyword(s):  
Immune Response ◽  
Immune System ◽  
Amino Acid ◽  
Measles Virus ◽  
Respiratory Infections ◽  
Viral Proteins ◽  
Cellular Protein ◽  
Amino Acid Sequences ◽  
Host Immune System ◽  
Human Immune

A comparative analysis on search for amino acid sequences in viral proteins causing respiratory infections (or respiratory infections syndrome) homologous to amino acid sequences from some human immune proteins was performed. The following viruses were used for comparative computer analysis: coronavirus (SARS-CoV), serotype C subgroup adenovirus C (adenoid 71 strain), measles virus (ICHINOSE-BA strain), rubella (Therien strain) and respiratory syncytial (B1 strain) virus. The search for homologous sequences in viral and human immune proteins was carried out by computer comparison of 12 amino acid fragments, which were assigned as homologous at identity in ≥ 8 positions. The data obtained showed that viral proteins contained homologous motifs in several host immune proteins involved in regulating both the inflammatory response and immune response. Mechanistically, all viruses studied were characterized by sequences homologous to host immune proteins such as complement system proteins, integrins, apoptosis inhibitory proteins, interleukins, and toll-like receptors. Such cellular proteins are actively involved in regulating host inflammatory process and immune response formation. Upon that, a set of host immune proteins, to which homologous fragments were found in viral proteins, was individual for each virus. Interestingly, the largest amount of homologous fragments (up to 20) was mainly concentrated in viral proteins with polymerase and protease activity suggesting that these proteins apart to their major role were involved in production of viral nucleic acids and might participate in regulating host immune system. Envelope, internal and non-structural viral proteins, homologous fragments were detected in much smaller quantities (from 1 to 4). In addition, two fragments homologous to various motifs of the same cellular protein were detected in some viral proteins. Thus, the data obtained further support our understanding that signs of immune system disorders in viral infections can result from multi-layered processes associated with modulation of host innate and adaptive immune system, and open up new approaches to study interaction of viruses with host immune system and identify new functions of viral proteins.

scholarly journals Development of Web Application for the Comparison of Segment Variability with Sequence Evolution and Immunogenic Properties for Highly Variable Proteins: An Application to Viruses

2021 ◽  
Author(s):  
Sumit Bala ◽  
Ambarnil Ghosh ◽  
Subhra Pradhan
Keyword(s):  
Experimental Research ◽  
Web Application ◽  
Structural Information ◽  
Solvent Accessibility ◽  
Viral Proteins ◽  
High Rate ◽  
Survival Strategies ◽  
Host Immune System ◽  
Application Development ◽  
The Web

AbstractHigh rate of mutation and structural flexibilities in viral proteins quickly make them resistant to the host immune system and existing antiviral strategies. For most of the pathogenic viruses, the key survival strategies lie in their ability to evolve rapidly through mutations that affects the protein structure and function. Along with the experimental research related to antiviral development, computational data mining also plays an important role in deciphering the molecular and genomic signatures of the viral adaptability. Uncovering conserved regions in viral proteins with diverse chemical and biological properties is an important area of research for developing antiviral therapeutics, though assigning those regions is not a trivial work. Advancement in protein structural information databases and repositories, made by experimental research accelerated the in-silico mining of the data to generate more integrative information. Despite of the huge effort on correlating the protein structural information with its sequence, it is still a challenge to defeat the high mutability and adaptability of the viral genomics structure. In this current study, the authors have developed a user-friendly web application interface that will allow users to study and visualize protein segment variabilities in viral proteins and may help to find antiviral strategies. The present work of web application development allows thorough mining of the surface properties and variabilities of viral proteins which in combination with immunogenicity and evolutionary properties make the visualization robust. In combination with previous research on 20-Dimensional Euclidian Geometry based sequence variability characterization algorithm, four other parameters has been considered for this platform: [1] predicted solvent accessibility information, [2] B-Cell epitopic potential, [3] T-Cell epitopic potential and [4] coevolving region of the viral protein. Uniqueness of this study lies in the fact that a protein sequence stretch is being characterized rather than single residue-based information, which helps to compare properties of protein segments with variability. In current work, as an example, beside presenting the web application platform, five proteins of SARS-CoV2 was presented with keeping focus on protein-S. Current web-application database contains 29 proteins from 7 viruses including a GitHub repository of the raw data used in this study. The web application is up and running in the following address: http://www.protsegvar.com.

scholarly journals A REVIEW ON APPLICATION OF NANOADJUVANT AS DELIVERY SYSTEM

2020 ◽  
pp. 24-33
Author(s):  
HITESH KUMAR DEWANGAN ◽  
SHUBHAM SINGH ◽  
ROHIT MISHRA ◽  
ROSHAN KUMAR DUBEY
Keyword(s):  
Viral Proteins ◽  
The Body ◽  
Lymphoid Tissues ◽  
Subunit Vaccines ◽  
Specific Immunity ◽  
Vaccine Potency ◽  
Polymeric Particles ◽  
Direct Targeting ◽  
Carrier Systems

Worldwide immunization can save millions of peoples to lives year by using the vaccines. The subunit of antigen components is manufactured which can stimulate the immune system by providing specific immunity against specific diseases. Subunit vaccines have many advantages like as high safety profile but having limited ability to provide immunogenicity. These traditional subunit vaccines activate only innate immunity, encourage cell-mediated transport of antigen to lymphoid tissues. Newly nano-adjuvants based vaccines carrier systems like liposomes, virosome, micelles, polymeric particles, protein, and peptides are developed by using various substances like viral proteins, polymer and polystyrene having immanent adjuvanticity and also provide exalted capability in manufacturing subunit vaccines. It has chromospheres substances that have various properties such as targeted, anti-damaging and caliber to lead immune reactions towards Th1 and Th2 route, which is an important feature for humoral as well as cellular immunity. The whole thing based on the carrier system, the role of nano-adjuvants, its pharmacokinetics and distribution in the body system. It has the ability to provide antigen-specific immunity to both systemic as well as mucosal by different vaccination passage. Also, the nano-adjuvants based vaccine suggested that direct targeting of antigen to improve the vaccine potency without sacrificing safety.

scholarly journals Electron Cryotomography Studies of Maturing HIV-1 Particles Reveal the Assembly Pathway of the Viral Core

2014 ◽  
Vol 89 (2) ◽  
pp. 1267-1277 ◽  
Author(s):  
Cora L. Woodward ◽  
Sarah N. Cheng ◽  
Grant J. Jensen
Keyword(s):  
Viral Genome ◽  
Virus Assembly ◽  
Structural Characteristics ◽  
Hexagonal Lattice ◽  
The Body ◽  
The Core ◽  
Assembly Pathway ◽  
Viral Particles ◽  
Electron Cryotomography ◽  
Hiv 1

ABSTRACTTo better characterize the assembly of the HIV-1 core, we have used electron cryotomography (ECT) to image infected cells and the viral particles cryopreserved next to them. We observed progressive stages of virus assembly and egress, including flower-like flat Gag lattice assemblies, hemispherical budding profiles, and virus buds linked to the plasma membrane via a thin membrane neck. The population of budded viral particles contains immature, maturation-intermediate, and mature core morphologies. Structural characteristics of the maturation intermediates suggest that the core assembly pathway involves the formation of a CA sheet that associates with the condensed ribonucleoprotein (RNP) complex. Our analysis also reveals a correlation between RNP localization within the viral particle and the formation of conical cores, suggesting that the RNP helps drive conical core assembly. Our findings support an assembly pathway for the HIV-1 core that begins with a small CA sheet that associates with the RNP to form the core base, followed by polymerization of the CA sheet along one side of the conical core toward the tip, and then closure around the body of the cone.IMPORTANCEDuring HIV-1 assembly and release, the Gag polyprotein is organized into a signature hexagonal lattice, termed the immature lattice. To become infectious, the newly budded virus must disassemble the immature lattice by proteolyzing Gag and then reassemble the key proteolytic product, the structural protein p24 (CA), into a distinct, mature hexagonal lattice during a process termed maturation. The mature HIV-1 virus contains a conical capsid that encloses the condensed viral genome at its wide base. Mutations or small molecules that interfere with viral maturation also disrupt viral infectivity. Little is known about the assembly pathway that results in the conical core and genome encapsidation. Here, we have used electron cryotomography to structurally characterize HIV-1 particles that are actively maturing. Based on the morphologies of core assembly intermediates, we propose that CA forms a sheet-like structure that associates with the condensed viral genome to produce the mature infectious conical core.

scholarly journals The SARS-CoV-2 Envelope and Membrane proteins modulate maturation and retention of the Spike protein, allowing assembly of virus-like particles

2020 ◽  
pp. jbc.RA120.016175
Author(s):  
Bertrand Boson ◽  
Vincent Legros ◽  
Bingjie Zhou ◽  
Eglantine Siret ◽  
Cyrille Mathieu ◽  
...  
Keyword(s):  
Secretory Pathway ◽  
Structural Proteins ◽  
Imaging Data ◽  
Virus Like Particles ◽  
Viral Particles ◽  
M Proteins ◽  
Infected Cells ◽  
Intermediate Compartment ◽  
Nucleoprotein N ◽  
Syncytia Formation

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a β-coronavirus, is the causative agent of the COVID-19 pandemic. Like for other coronaviruses, its particles are composed of four structural proteins: Spike (S), Envelope (E), Membrane (M) and Nucleoprotein (N) proteins. The involvement of each of these proteins and their interactions are critical for assembly and production of β-coronavirus particles. Here, we sought to characterize the interplay of SARS-CoV-2 structural proteins during the viral assembly process. By combining biochemical and imaging assays in infected vs. transfected cells, we show that E and M regulate intracellular trafficking of S as well as its intracellular processing. Indeed, the imaging data reveal that S is re-localized at endoplasmic reticulum (ER)-Golgi intermediate compartment (ERGIC) or Golgi compartments upon co-expression of E or M, as observed in SARS-CoV-2-infected cells, which prevents syncytia formation. We show that a C-terminal retrieval motif in the cytoplasmic tail of S is required for its M-mediated retention in the ERGIC, whereas E induces S retention by modulating the cell secretory pathway. We also highlight that E and M induce a specific maturation of N-glycosylation of S, independently of the regulation of its localization, with a profile that is observed both in infected cells and in purified viral particles. Finally, we show that E, M and N are required for optimal production of virus- like-particles. Altogether, these results highlight how E and M proteins may influence the properties of S proteins and promote the assembly of SARS-CoV-2 viral particles.

Assessment of the Best Compatible Dialysis System: Feasible Application for Bioelectrical Impedance

1995 ◽  
Vol 18 (11) ◽  
pp. 712-715
Author(s):  
G. Bazzato ◽  
F. Scanferla
Keyword(s):  
Bioelectrical Impedance ◽  
Well Being ◽  
Progressive Increase ◽  
The Body ◽  
Crucial Aspect ◽  
Dialysis Adequacy ◽  
Blood Tests ◽  
Clinical Events ◽  
Close Relationship ◽  
Humoral Responses

Since the introduction of hemodialysis procedure several attempts have been made to elucidate the material tissue interaction in order to evaluate the behaviour of immunosystem cellular and humoral responses to the material of patients on renal replacement therapy. Biochemical and sierological parameters have been considered as method for assessment of the best compatible dialysis. Nevertheless blood tests don't probably reflect the most important symptoms of clinical relevance. Thus we have applied bioelectrical impedance to assess the whole procedure/patient system. Resistance (R) changes during hemodialysis resulted strictly inversely correlated to the body weight variations during HD session (R < 0.96). Reactance (Xc) has also shown a progressive increase associated with an increment of phase angle, while Xc during clinical events such as hypotension, vomiting or cramps showed some transient falls. Also nutritional status and clinical well-being manifested a close relationship with bioelectrical parameters. It is therefore our feeling that BIA monitoring will provide a feasible tool to assess dialysis adequacy, of which biocompatibility represent a crucial aspect.

The Clinical Application Value of Multiple Combination Food Intolerance Testing

2020 ◽  
Author(s):  
Shudong LIN ◽  
Xiujing YANG ◽  
Ying XING ◽  
Xingye WANG ◽  
Yadong LI
Keyword(s):  
Gastrointestinal Symptoms ◽  
Egg White ◽  
The Body ◽  
Food Intolerance ◽  
Igg Antibodies ◽  
Significant Difference ◽  
Positive Rate ◽  
Specific Igg ◽  
Symptom Group ◽  
Specific Igg Antibodies

Background: We aimed to investigate the clinical value of detecting 14 food intolerances. Methods: A total of 312 patients with food intolerance enrolled in the Third Affiliated Hospital of Qiqihar Medical University (Qiqihar, China) from Feb 2016 to Feb 2017 were selected. ELISA was used to detect intolerance specific IgG antibodies for 14 foods (pork, chicken, beef, shrimp, fish, crab, egg white/yolk, tomato, mushroom, milk, corn, rice, soybean, wheat). Results: The highest average positive rate of the patients was 42.31% for the crab, followed by shrimp 21.15%, egg white/yolk 18.27% and milk 16.99%. The positive rate from high to low was crab, shrimp, egg white/yolk, milk, fish, corn, soybeans, tomatoes, rice, mushrooms, wheat, pork, beef, chicken. There were significant differences in the specific IgG antibody positive rates between shrimp, soybean and wheat in the skin symptoms group, gastrointestinal symptoms group, respiratory symptom group and nervous system symptom group (P<0.05). There was a significant difference in the positive rate of specific IgG antibodies between shrimp, crab and egg white/yolk in the adolescent group, the middle-aged group and the elderly group (P<0.05). Conclusion: The detection of food-specific IgG antibodies can help to determine which food intolerance caused the disease, and then adopt a fasting or diet method to avoid eating unsuitable foods and continually damaging the body, thus maintaining good health. The detection method provides a new idea for the diagnosis and prevention of diseases.

scholarly journals Trade-Offs for Viruses in Overcoming Innate Immunities in Plants

2016 ◽  
Vol 29 (8) ◽  
pp. 595-598 ◽  
Author(s):  
Yuri Miyashita ◽  
Go Atsumi ◽  
Kenji S. Nakahara
Keyword(s):  
Immune System ◽  
Adaptive Evolution ◽  
Viral Protein ◽  
Viral Proteins ◽  
Host Immune System ◽  
Immune Receptor ◽  
Immune Systems ◽  
Trade Offs ◽  
Molecular Patterns ◽  
Increased Susceptibility

Plants recognize viral infection via an immune receptor, i.e., nucleotide-binding site (NB)-leucine-rich repeat (LRR) proteins. Another immune receptor, receptor-like kinase proteins, which share an LRR domain with NB-LRRs, perceive conserved molecules of pathogens called pathogen- or microbe-associated molecular patterns, but NB-LRRs generally perceive particular viral proteins. As viruses can evolve more rapidly than the host immune system, how do plant immune systems, which rely on the perception of proteins, remain effective? Viral adaptive evolution may be controlled by penalties that result from mutations in viral proteins that are perceived by NB-LRRs. Our recent studies in pea (Pisum sativum) suggest a penalty of increased susceptibility to another immune system. When a viral protein mutates to evade one immune system, the virus with the mutated protein becomes more susceptible to another. Such antagonistic pleiotropy of a viral protein by two independent plant immune systems may have precedents. Plants may rely on pairs of immune systems to constrain adaptive evolution by viruses and thereby maintain durable antiviral immunity.

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