COVID-19 : histoire, pathogenèse et réponse immunitaire de l'hôte

By the end of 2019, pneumonia of unknown etiology occurred in Wuhan, China. Local hospitals started receiving patients presenting symptoms like dry cough, fatigue, and breathing difficulties, most of these patients were linked to the Huanan seafood market, Wuhan, China. The pandemic was afterward confirmed to be associated with a novel coronavirus. The virus spread quickly from Wuhan to other provinces of China, then from china to the rest of the world causing thereby one of the most brutal pandemics in the world’s history. SARS-CoV2 has a long incubation period ranging from 3 to 7 days and can go up to 14 days in some cases which makes the infection difficult to be detected early and subsequently the disease spread harder to be controlled. SARS-CoV-2 is a single-stranded RNA virus with 4 main structural proteins, the spike (S) glycoprotein, the small envelope (E) the glycoprotein, the membrane (M) glycoprotein as well as the nucleocapsid (N) protein. Current knowledge about the virus shows that it uses its spike protein to invade host cells, mainly the alveolar epithelial cells. The the lung is the most targeted organ among many other organs like the heart, small intestine, and kidneys that are vulnerable to SARS-CoV-2 infection. The COVID-19 is known to be mild in most cases, but in some cases, it can be severe or even fatal. In the severe cases, acute respiratory distress syndrome was reported, and the the capability of SARS-CoV-2 to infect many organs can lead to multiorgan failure and death. SARS-CoV-2 invasion induces several immune responses that could be efficient for infection clearance in mild cases, while in severe cases, the immune response dysfunctions can even contribute to the disease aggravation. Neither the the pathogenic mechanism by which SARS-CoV-2 infects host cells, nor the host immune response to its infection have been fully understood, hence further studies are needed to give further evidence about these two phenomena. Keywords: COVID-19, SARS-CoV-2, Coronavirus, Structural proteins, Immune response.

Download Full-text

Epigenetic Lens to Visualize the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) Infection in COVID-19 Pandemic

Frontiers in Genetics ◽

10.3389/fgene.2021.581726 ◽

2021 ◽

Vol 12 ◽

Author(s):

Nitin Saksena ◽

Srinivasa Reddy Bonam ◽

Monica Miranda-Saksena

Keyword(s):

Immune Response ◽

Current Knowledge ◽

Rna Virus ◽

Expression Patterns ◽

Host Cells ◽

Human Populations ◽

Host Interactions ◽

Epigenetic Machinery ◽

Immune Sensing ◽

Post Entry

In <20 years, we have witnessed three different epidemics with coronaviruses, SARS-CoV, MERS-CoV, and SARS-CoV-2 in human populations, causing widespread mortality. SARS-CoV-2, through its rapid global spread, has led to the pandemic that we call COVID-19. As of February 1, 2021, the global infections linked to SARS-CoV-2 stand at 103,503,340, with 2,236,960 deaths, and 75,108,099 recoveries. This review attempts to highlight host-pathogen interaction with particular emphasis on the role of epigenetic machinery in regulating the disease. Although researchers, since the start of the pandemic, have been intensely engaged in diverse areas to understand the mechanisms involved in SARS-CoV-2 infection to find answers that can bring about innovative ways to swiftly treat and prevent disease progression, this review provides an overview on how the host epigenetics is modulated and subverted by SARS-CoV-2 to enter the host cells and drive immunopathogenesis. Epigenetics is the study that combines genetic and non-genetic factors controlling phenotypic variation, which are primarily a consequence of external and environmental stimuli. These stimuli alter the activity of a gene without impinging on the DNA code. In viral-host interactions, DNA/RNA methylation, non-coding RNAs, chromatin remodeling, and histone modifications are known to regulate and modulate host gene expression patterns. Viruses such as Coronaviruses (an RNA virus) show intrinsic association with these processes. They have evolved the ability to tamper with host epigenetic machinery to interfere with immune sensing pathways to evade host immune response, thereby enhancing its replication and pathogenesis post-entry. These epigenetic alterations allow the virus to weaken the host's immune response to successfully spread infection. How this occurs, and what epigenetic mechanisms are altered is poorly understood both for coronaviruses and other respiratory RNA viruses. The review highlights several cutting-edge aspects of epigenetic work primarily pertinent to SARS-CoV-2, which has been published between 2019 and 2020 to showcase the current knowledge both in terms of success and failures and take lessons that will assist us in understanding the disease to develop better treatments suited to kill SARS-CoV-2.

Download Full-text

Is the kidney a target of SARS-CoV-2?

AJP Renal Physiology ◽

10.1152/ajprenal.00160.2020 ◽

2020 ◽

Vol 318 (6) ◽

pp. F1454-F1462 ◽

Cited By ~ 42

Author(s):

Miguel Angel Martinez-Rojas ◽

Olynka Vega-Vega ◽

Norma A. Bobadilla

Keyword(s):

Current Knowledge ◽

Multiorgan Failure ◽

Kidney Injury ◽

Host Cells ◽

Cellular Receptor ◽

Tubular Epithelial Cells ◽

Severe Respiratory Distress ◽

Angiotensin Converting Enzyme 2 ◽

Biological Aspects ◽

Renal Abnormalities

The new disease produced by severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) represents a major pandemic event nowadays. Since its origin in China in December 2019, there is compelling evidence that novel SARS-CoV-2 is a highly transmissible virus, and it is associated to a broad clinical spectrum going from subclinical presentation to severe respiratory distress and multiorgan failure. Like other coronaviruses, SARS-CoV-2 recognizes human angiotensin-converting enzyme 2 as a cellular receptor that allows it to infect different host cells and likely disrupts renin-angiotensin-aldosterone system homeostasis. Particularly, a considerable incidence of many renal abnormalities associated to COVID-19 has been reported, including proteinuria, hematuria, and acute kidney injury. Moreover, it has been recently demonstrated that SARS-CoV-2 can infect podocytes and tubular epithelial cells, which could contribute to the development of the aforementioned renal abnormalities. In this review, we discuss the biological aspects of SARS-CoV-2 infection, how understanding current knowledge about SARS-CoV-2 infection may partly explain the involvement of the kidneys in the pathophysiology of COVID-19, and what questions have arisen and remain to be explored.

Download Full-text

Immunity to Bovine Herpesvirus 1: I. Viral lifecycle and innate immunity

Animal Health Research Reviews ◽

10.1017/s1466252313000042 ◽

2013 ◽

Vol 14 (1) ◽

pp. 88-102 ◽

Cited By ~ 17

Author(s):

Randall L. Levings ◽

James A. Roth

Keyword(s):

Immune Response ◽

Latent Infection ◽

Bovine Herpesvirus ◽

Lytic Replication ◽

Host Cells ◽

Type I Interferons ◽

Disease Spread ◽

Type I ◽

Bovine Herpesvirus 1 ◽

Herpesvirus 1

AbstractBovine herpesvirus 1 (BHV-1) causes a variety of diseases and is globally distributed. It infects via mucosal epithelium, leading to rapid lytic replication and latent infection, primarily in sensory ganglia. Large amounts of virus can be excreted by the host on primary infection or upon recrudescence of latent infection, resulting in disease spread. The bovine immune response to BHV-1 is rapid, robust, balanced, and long-lasting. The innate immune system is the first to respond to the infection, with type I interferons (IFNs), inflammatory cytokines, killing of infected host cells, and priming of a balanced adaptive immune response. The virus possesses a variety of immune evasion strategies, including inhibition of type I IFN production, chemokine and complement binding, infection of macrophages and neutrophils, and latency. BHV-1 immune suppression contributes to the severity of its disease manifestations and to the bovine respiratory disease complex, the leading cause of cattle death loss in the USA.

Download Full-text

Innate Immunity Evasion Strategies of Highly Pathogenic Coronaviruses: SARS-CoV, MERS-CoV, and SARS-CoV-2

Frontiers in Microbiology ◽

10.3389/fmicb.2021.770656 ◽

2021 ◽

Vol 12 ◽

Author(s):

Jin-Yan Li ◽

Zhi-Jian Zhou ◽

Qiong Wang ◽

Qing-Nan He ◽

Ming-Yi Zhao ◽

...

Keyword(s):

Immune Response ◽

Pattern Recognition ◽

Current Knowledge ◽

Viral Pathogenesis ◽

Host Cells ◽

Highly Pathogenic ◽

Cellular Processes ◽

Antiviral Therapies ◽

The Past ◽

Human Coronaviruses

In the past two decades, coronavirus (CoV) has emerged frequently in the population. Three CoVs (SARS-CoV, MERS-CoV, SARS-CoV-2) have been identified as highly pathogenic human coronaviruses (HP-hCoVs). Particularly, the ongoing COVID-19 pandemic caused by SARS-CoV-2 warns that HP-hCoVs present a high risk to human health. Like other viruses, HP-hCoVs interact with their host cells in sophisticated manners for infection and pathogenesis. Here, we reviewed the current knowledge about the interference of HP-hCoVs in multiple cellular processes and their impacts on viral infection. HP-hCoVs employed various strategies to suppress and evade from immune response, including shielding viral RNA from recognition by pattern recognition receptors (PRRs), impairing IFN-I production, blocking the downstream pathways of IFN-I, and other evasion strategies. This summary provides a comprehensive view of the interplay between HP-hCoVs and the host cells, which is helpful to understand the mechanism of viral pathogenesis and develop antiviral therapies.

Download Full-text

Extracellular Vesicles in Viral Spread and Antiviral Response

Viruses ◽

10.3390/v12060623 ◽

2020 ◽

Vol 12 (6) ◽

pp. 623 ◽

Cited By ~ 5

Author(s):

Raquel Bello-Morales ◽

Inés Ripa ◽

José Antonio López-Guerrero

Keyword(s):

Immune Response ◽

Extracellular Vesicles ◽

Current Knowledge ◽

Host Immune Response ◽

Host Cells ◽

Viral Spread ◽

Viral Responses ◽

Hsv 1

Viral spread by both enveloped and non-enveloped viruses may be mediated by extracellular vesicles (EVs), including microvesicles (MVs) and exosomes. These secreted vesicles have been demonstrated to be an efficient mechanism that viruses can use to enter host cells, enhance spread or evade the host immune response. However, the complex interplay between viruses and EVs gives rise to antagonistic biological tasks—to benefit the viruses, enhancing infection and interfering with the immune system or to benefit the host, by mediating anti-viral responses. Exosomes from cells infected with herpes simplex type 1 (HSV-1) may transport viral and host transcripts, proteins and innate immune components. This virus may also use MVs to expand its tropism and evade the host immune response. This review aims to describe the current knowledge about EVs and their participation in viral infection, with a specific focus on the role of exosomes and MVs in herpesvirus infections, particularly that of HSV-1.

Download Full-text

Modulation of the Host Immune Response by Schistosome Egg-Secreted Proteins Is a Critical Avenue of Host–Parasite Communication

Pathogens ◽

10.3390/pathogens10070863 ◽

2021 ◽

Vol 10 (7) ◽

pp. 863

Author(s):

Jack P. Carson ◽

Geoffrey N. Gobert

Keyword(s):

Immune Response ◽

Current Knowledge ◽

Host Immune Response ◽

Egg Laying ◽

Host Cells ◽

Future Application ◽

Mammalian Host ◽

Immunomodulatory Activity ◽

Host Immune System

During a schistosome infection, the interactions that occur between the mammalian host and the parasite change rapidly once egg laying begins. Both juvenile and adult schistosomes adapt to indefinitely avoid the host immune system. In contrast, the survival of eggs relies on quickly traversing from the host. Following the commencement of egg laying, the host immune response undergoes a shift from a type 1 helper (Th1) inflammatory response to a type 2 helper (Th2) granulomatous response. This change is driven by immunomodulatory proteins within the egg excretory/secretory products (ESPs), which interact with host cells and alter their behaviour to promote egg translocation. However, in parallel, these ESPs also provoke the development of chronic schistosomiasis pathology. Recent studies using high-throughput proteomics have begun to characterise the components of schistosome egg ESPs, particularly those of Schistosoma mansoni, S. japonicum and S. haematobium. Future application of this knowledge may lead to the identification of proteins with novel immunomodulatory activity or pathological importance. However, efforts in this area are limited by a lack of in situ or in vivo functional characterisation of these proteins. This review will highlight the current knowledge of the content and demonstrated functions of schistosome egg ESPs.

Download Full-text

Immunoinformatic approach to design a multiepitope vaccine targeting non-mutational hotspot regions of structural and non-structural proteins of the SARS CoV2

PeerJ ◽

10.7717/peerj.11126 ◽

2021 ◽

Vol 9 ◽

pp. e11126

Author(s):

Vandana Solanki ◽

Monalisa Tiwari ◽

Vishvanath Tiwari

Keyword(s):

Immune Response ◽

Binding Affinity ◽

Antigen Processing ◽

Clonal Selection ◽

3D Structure ◽

Host Cells ◽

Dynamics Simulation ◽

Structural Proteins ◽

Morbidity Rate ◽

Subtractive Proteomics

Background The rapid Severe Acute Respiratory Syndrome Coronavirus 2 (SARS CoV2) outbreak caused severe pandemic infection worldwide. The high mortality and morbidity rate of SARS CoV2 is due to the unavailability of vaccination and mutation in this virus. The present article aims to design a potential vaccine construct VTC3 targeting the non-mutational region of structural and non-structural proteins of SARS CoV2. Methods In this study, vaccines were designed using subtractive proteomics and reverse vaccinology. To target the virus adhesion and evasion, 10 different structural and non-structural proteins have been selected. Shortlisted proteins have been screened for B cell, T cell and IFN gamma interacting epitopes. 3D structure of vaccine construct was modeled and evaluated for its physicochemical properties, immunogenicity, allergenicity, toxicity and antigenicity. The finalized construct was implemented for docking and molecular dynamics simulation (MDS) with different toll-like receptors (TLRs) and human leukocyte antigen (HLA). The binding energy and dissociation construct of the vaccine with HLA and TLR was also calculated. Mutational sensitivity profiling of the designed vaccine was performed, and mutations were reconfirmed from the experimental database. Antibody production, clonal selection, antigen processing, immune response and memory generation in host cells after injection of the vaccine was also monitored using immune simulation. Results Subtractive proteomics identified seven (structural and non-structural) proteins of this virus that have a role in cell adhesion and infection. The different epitopes were predicted, and only extracellular epitopes were selected that do not have similarity and cross-reactivity with the host cell. Finalized epitopes of all proteins with minimum allergenicity and toxicity were joined using linkers to designed different vaccine constructs. Docking different constructs with different TLRs and HLA demonstrated a stable and reliable binding affinity of VTC3 with the TLRs and HLAs. MDS analysis further confirms the interaction of VTC3 with HLA and TLR1/2 complex. The VTC3 has a favorable binding affinity and dissociation constant with HLA and TLR. The VTC3 does not have similarities with the human microbiome, and most of the interacting residues of VTC3 do not have mutations. The immune simulation result showed that VTC3 induces a strong immune response. The present study designs a multiepitope vaccine targeting the non-mutational region of structural and non-structural proteins of the SARS CoV2 using an immunoinformatic approach, which needs to be experimentally validated.

Download Full-text

Roles of the Non-Structural Proteins of Influenza A Virus

Pathogens ◽

10.3390/pathogens9100812 ◽

2020 ◽

Vol 9 (10) ◽

pp. 812

Author(s):

Wenzhuo Hao ◽

Lingyan Wang ◽

Shitao Li

Keyword(s):

Influenza A Virus ◽

Influenza A ◽

Rna Virus ◽

Critical Role ◽

Viral Proteins ◽

Host Cells ◽

Structural Proteins ◽

Host Interactions ◽

New Findings ◽

Seasonal Epidemics

Influenza A virus (IAV) is a segmented, negative single-stranded RNA virus that causes seasonal epidemics and has a potential for pandemics. Several viral proteins are not packed in the IAV viral particle and only expressed in the infected host cells. These proteins are named non-structural proteins (NSPs), including NS1, PB1-F2 and PA-X. They play a versatile role in the viral life cycle by modulating viral replication and transcription. More importantly, they also play a critical role in the evasion of the surveillance of host defense and viral pathogenicity by inducing apoptosis, perturbing innate immunity, and exacerbating inflammation. Here, we review the recent advances of these NSPs and how the new findings deepen our understanding of IAV–host interactions and viral pathogenesis.

Download Full-text

Respiratory epithelium: Place of entry and / or defense against SARS-CoV-2 virus

Praxis medica ◽

10.5937/pramed2102035l ◽

2021 ◽

Vol 50 (1-2) ◽

pp. 35-43

Author(s):

Snežana Leštarević ◽

Slađana Savić ◽

Leonida Vitković ◽

Predrag Mandić ◽

Milica Mijović ◽

...

Keyword(s):

Immune Response ◽

Epithelial Cells ◽

Innate Immune Response ◽

Alveolar Macrophages ◽

Rna Virus ◽

The Body ◽

Innate Immune ◽

Alveolar Epithelial Cells ◽

Biologically Active ◽

Lung Damage

Coronavirus Disease (COVID-19) is caused by the RNA virus SARS-CoV-2. The primary receptor for the virus is most likely Angiotensin-converting enzyme 2 (ACE2), and the virus enters the body by infecting epithelial cells of the respiratory tract. Through the activation of Toll Like Receptors (TLRs), epithelial cells begin to synthesize various biologically active molecules. The pathophysiology of the COVID 19 is primarily attributed to the hyperactivation of host's immune system due to direct damage to the cells, with consequent release of proinflammatory substances, but also due to the activation of the innate immune response through the activation of alveolar macrophages and dendrite cells (DC). A strong proinflammatory reaction causes damage to alveolar epithelial cells and vascular endothelium. Respiratory epithelial cells, alveolar macrophages and DC are likely to be the most important cells involved in the innate immune response to the virus, since prolonged and excessive SARS-CoV-2-induced activation of these cells leads to the secretion of cytokines and chemokines that massively attract leukocytes and monocytes to the lungs and cause lung damage.

Download Full-text

Emerging Strains Of SARS-Cov2 And Their Inhibition by The Use of Phytochemicals: An In-Silico Analysis

10.21203/rs.3.rs-523184/v1 ◽

2021 ◽

Author(s):

Mohammad Faheem Khan ◽

Tanveer Ahamad ◽

Waseem Ahmad Ansari ◽

Mohsin Ali Khan ◽

Zaw Ali Khan ◽

...

Keyword(s):

Rna Virus ◽

In Silico Analysis ◽

Open Reading Frames ◽

Host Cells ◽

Structural Proteins ◽

Angiotensin Converting Enzyme 2 ◽

A Genome ◽

Infectivity Rate ◽

Silico Analysis ◽

Prime Target

Abstract Recently identified coronavirus namely severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a single-stranded positive-sense RNA virus with a genome of 29.9 kb in size encoding 14 open reading frames (ORFs) and 27 different structural and non-structural proteins. Among the structural proteins, trimeric-shaped spike glycoprotein is responsible for the entry of the SARS-CoV2 genome into host cells by interacting with human angiotensin-converting enzyme 2 (ACE2) receptors that are present on the cell surface with high affinity. Notably, inhibition of spike protein is considered a prime target for the development of drugs against COVID-19. Viruses can mutate, and SARS-CoV-2 is no exception. Since the first whole genome of SARS-CoV2 was published in February 2020, at least 4400 amino acid substitutions and several thousand mutations have been identified to date. As of today, more than 3500 new variants of SARS-CoV2 have been sequenced with a high spreading and infectivity rate which makes the virus more contagious. These new variants have been spread to several countries including United States (US), United Kingdom (UK), Brazil, South Africa, India, and other countries, etc. Therefore, herein, we analysed the new SARS-CoV2 strains, constructed the 3D homology models of Brazil P.1 and Indian B.1.617 variants, and screened them against 100 phytochemicals having previously identified anti-viral activity. Our study revealed that the top three phytochemicals for each of the new strains might serve as potential anti- SARS-CoV-2 agents for further drug discovery and development process to tackle COVID-19.

Download Full-text