Viruses

Editorial

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3 pages, 195 KiB

Open AccessEditorial

Special Issue “SARS-CoV-2 Innate and Adaptive Immune Responses”

by Rémi Planes and Elmostafa Bahraoui

Viruses 2022, 14(11), 2363; https://doi.org/10.3390/v14112363 - 26 Oct 2022

Cited by 1 | Viewed by 1170

Abstract

Since the end of 2019, humanity has been facing the emergence of a new large positive-sense, single-stranded RNA virus called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes a respiratory disease with substantial morbidity and mortality called coronavirus disease 19 (COVID-19) [...] [...] Read more.

Since the end of 2019, humanity has been facing the emergence of a new large positive-sense, single-stranded RNA virus called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes a respiratory disease with substantial morbidity and mortality called coronavirus disease 19 (COVID-19) [...] Full article

(This article belongs to the Special Issue SARS-CoV-2 Innate and Adaptive Immune Responses)

Research

Jump to: Editorial, Review

13 pages, 1195 KiB

Open AccessArticle

Role of Genetic Polymorphism Present in Macrophage Activation Syndrome Pathway in Post Mortem Biopsies of Patients with COVID-19

by Aline Cristina Zanchettin, Leonardo Vinicius Barbosa, Anderson Azevedo Dutra, Daniele Margarita Marani Prá, Marcos Roberto Curcio Pereira, Rebecca Benicio Stocco, Ana Paula Camargo Martins, Caroline Busatta Vaz de Paula, Seigo Nagashima, Lucia de Noronha and Cleber Machado-Souza

Viruses 2022, 14(8), 1699; https://doi.org/10.3390/v14081699 - 31 Jul 2022

Cited by 6 | Viewed by 2251

Abstract

COVID-19 is a viral disease associated with an intense inflammatory response. Macrophage Activation Syndrome (MAS), the complication present in secondary hemophagocytic lymphohistiocytosis (sHLH), shares many clinical aspects observed in COVID-19 patients, and investigating the cytolytic function of the responsible cells for the first [...] Read more.

COVID-19 is a viral disease associated with an intense inflammatory response. Macrophage Activation Syndrome (MAS), the complication present in secondary hemophagocytic lymphohistiocytosis (sHLH), shares many clinical aspects observed in COVID-19 patients, and investigating the cytolytic function of the responsible cells for the first line of the immune response is important. Formalin-fixed paraffin-embedded lung tissue samples obtained by post mortem necropsy were accessed for three groups (COVID-19, H1N1, and CONTROL). Polymorphisms in MAS cytolytic pathway (PRF1; STX11; STXBP2; UNC13D and GZMB) were selected and genotyping by TaqMan^® assays (Thermo Fisher Scientific, MA, USA) using Real-Time PCR (Applied Biosystems, MA USA). Moreover, immunohistochemistry staining was performed with a monoclonal antibody against perforin, CD8+ and CD57+ proteins. Histopathological analysis showed high perforin tissue expression in the COVID-19 group; CD8+ was high in the H1N1 group and CD57+ in the CONTROL group. An association could be observed in two genes related to the cytolytic pathway (PRF1 rs885822 G/A and STXBP2 rs2303115 G/A). Furthermore, PRF1 rs350947132 was associated with increased immune tissue expression for perforin in the COVID-19 group. The genotype approach could help identify patients that are more susceptible, and for this reason, our results showed that perforin and SNPs in the PRF1 gene can be involved in this critical pathway in the context of COVID-19. Full article

(This article belongs to the Special Issue SARS-CoV-2 Innate and Adaptive Immune Responses)

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9 pages, 1264 KiB

Open AccessArticle

SARS-CoV-2 Omicron Induces Enhanced Mucosal Interferon Response Compared to other Variants of Concern, Associated with Restricted Replication in Human Lung Tissues

by Or Alfi, Marah Hamdan, Ori Wald, Arkadi Yakirevitch, Ori Wandel, Esther Oiknine-Djian, Ben Gvili, Hadas Knoller, Noa Rozendorn, Hadar Golan Berman, Sheera Adar, Olesya Vorontsov, Michal Mandelboim, Zichria Zakay-Rones, Menachem Oberbaum, Amos Panet and Dana G. Wolf

Viruses 2022, 14(7), 1583; https://doi.org/10.3390/v14071583 - 21 Jul 2022

Cited by 13 | Viewed by 2527

Abstract

SARS-CoV-2 Omicron variant has been characterized by decreased clinical severity, raising the question of whether early variant-specific interactions within the mucosal surfaces of the respiratory tract could mediate its attenuated pathogenicity. Here, we employed ex vivo infection of native human nasal and lung [...] Read more.

SARS-CoV-2 Omicron variant has been characterized by decreased clinical severity, raising the question of whether early variant-specific interactions within the mucosal surfaces of the respiratory tract could mediate its attenuated pathogenicity. Here, we employed ex vivo infection of native human nasal and lung tissues to investigate the local-mucosal susceptibility and innate immune response to Omicron compared to Delta and earlier SARS-CoV-2 variants of concern (VOC). We show that the replication of Omicron in lung tissues is highly restricted compared to other VOC, whereas it remains relatively unchanged in nasal tissues. Mechanistically, Omicron induced a much stronger antiviral interferon response in infected tissues compared to Delta and earlier VOC-a difference, which was most striking in the lung tissues, where the innate immune response to all other SARS-CoV-2 VOC was blunted. Notably, blocking the innate immune signaling restored Omicron replication in the lung tissues. Our data provide new insights to the reduced lung involvement and clinical severity of Omicron. Full article

(This article belongs to the Special Issue SARS-CoV-2 Innate and Adaptive Immune Responses)

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16 pages, 2131 KiB

Open AccessCommunication

High and Sustained Ex Vivo Frequency but Altered Phenotype of SARS-CoV-2-Specific CD4⁺ T-Cells in an Anti-CD20-Treated Patient with Prolonged COVID-19

by Leon Cords, Maximilian Knapp, Robin Woost, Sophia Schulte, Silke Kummer, Christin Ackermann, Claudia Beisel, Sven Peine, Alexandra Märta Johansson, William Wai-Hung Kwok, Thomas Günther, Nicole Fischer, Melanie Wittner, Marylyn Martina Addo, Samuel Huber and Julian Schulze zur Wiesch

Viruses 2022, 14(6), 1265; https://doi.org/10.3390/v14061265 - 10 Jun 2022

Cited by 5 | Viewed by 4746

Abstract

Here, we longitudinally assessed the ex vivo frequency and phenotype of SARS-CoV-2 membrane protein (aa145–164) epitope-specific CD4⁺ T-cells of an anti-CD20-treated patient with prolonged viral positivity in direct comparison to an immunocompetent patient through an MHC class II DRB1*11:01 Tetramer analysis. We [...] Read more.

Here, we longitudinally assessed the ex vivo frequency and phenotype of SARS-CoV-2 membrane protein (aa145–164) epitope-specific CD4⁺ T-cells of an anti-CD20-treated patient with prolonged viral positivity in direct comparison to an immunocompetent patient through an MHC class II DRB1*11:01 Tetramer analysis. We detected a high and stable SARS-CoV-2 membrane-specific CD4⁺ T-cell response in both patients, with higher frequencies of virus-specific CD4⁺ T-cells in the B-cell-depleted patient. However, we found an altered virus-specific CD4⁺ T-cell memory phenotype in the B-cell-depleted patient that was skewed towards late differentiated memory T-cells, as well as reduced frequencies of SARS-CoV-2-specific CD4⁺ T-cells with CD45RA⁻ CXCR5⁺ PD-1⁺ circulating T follicular helper cell (cT_FH) phenotype. Furthermore, we observed a delayed contraction of CD127⁻ virus-specific effector cells. The expression of the co-inhibitory receptors TIGIT and LAG-3 fluctuated on the virus-specific CD4⁺ T-cells of the patient, but were associated with the inflammation markers IL-6 and CRP. Our findings indicate that, despite B-cell depletion and a lack of B-cell—T-cell interaction, a robust virus-specific CD4⁺ T-cell response can be primed that helps to control the viral replication, but which is not sufficient to fully abrogate the infection. Full article

(This article belongs to the Special Issue SARS-CoV-2 Innate and Adaptive Immune Responses)

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19 pages, 3937 KiB

Open AccessArticle

SARS-CoV-2 Envelope (E) Protein Binds and Activates TLR2 Pathway: A Novel Molecular Target for COVID-19 Interventions

by Rémi Planès, Jean-Baptiste Bert, Sofiane Tairi, Lbachir BenMohamed and Elmostafa Bahraoui

Viruses 2022, 14(5), 999; https://doi.org/10.3390/v14050999 - 8 May 2022

Cited by 32 | Viewed by 3502

Abstract

This paper presents a molecular characterization of the interaction between the SARS-CoV-2 envelope (E) protein and TLR2. We demonstrated that the E protein, both as a recombinant soluble protein and as a native membrane protein associated with SARS-CoV-2 viral particles, interacts physically with [...] Read more.

This paper presents a molecular characterization of the interaction between the SARS-CoV-2 envelope (E) protein and TLR2. We demonstrated that the E protein, both as a recombinant soluble protein and as a native membrane protein associated with SARS-CoV-2 viral particles, interacts physically with the TLR2 receptor in a specific and dose-dependent manner. Furthermore, we showed that the specific interaction with the TLR2 pathway activates the NF-κB transcription factor and stimulates the production of the CXCL8 inflammatory chemokine. In agreement with the importance of NF-κB in the TLR signaling pathway, we showed that the chemical inhibition of this transcription factor leads to significant inhibition of CXCL8 production, while the blockade of the P38 and ERK1/2 MAP kinases only results in partial CXCL8 inhibition. Overall, our findings propose the envelope (E) protein as a novel molecular target for COVID-19 interventions: either (i) by exploring the therapeutic effect of anti-E blocking/neutralizing antibodies in symptomatic COVID-19 patients, or (ii) as a promising non-spike SARS-CoV-2 antigen candidate for inclusion in the development of next-generation prophylactic vaccines against COVID-19 infection and disease. Full article

(This article belongs to the Special Issue SARS-CoV-2 Innate and Adaptive Immune Responses)

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13 pages, 1935 KiB

Open AccessArticle

Longitudinal Analysis of Neutralizing Potency against SARS-CoV-2 in the Recovered Patients after Treatment with or without Favipiravir

by Kanako Shinada, Takashi Sato, Saya Moriyama, Yu Adachi, Masahiro Shinoda, Shinichiro Ota, Miwa Morikawa, Masamichi Mineshita, Takayuki Matsumura, Yoshimasa Takahashi and Masaharu Shinkai

Viruses 2022, 14(4), 670; https://doi.org/10.3390/v14040670 - 24 Mar 2022

Cited by 2 | Viewed by 2628

Abstract

The effect of treatment with favipiravir, an antiviral purine nucleoside analog, for coronavirus disease 2019 (COVID-19) on the production and duration of neutralizing antibodies for SARS-CoV-2 was explored. There were 17 age-, gender-, and body mass index-matched pairs of favipiravir treated versus control [...] Read more.

The effect of treatment with favipiravir, an antiviral purine nucleoside analog, for coronavirus disease 2019 (COVID-19) on the production and duration of neutralizing antibodies for SARS-CoV-2 was explored. There were 17 age-, gender-, and body mass index-matched pairs of favipiravir treated versus control selected from a total of 99 patients recovered from moderate COVID-19. These subjects participated in the longitudinal (>6 months) analysis of (i) SARS-CoV-2 spike protein’s receptor-binding domain IgG, (ii) virus neutralization assay using authentic virus, and (iii) neutralization potency against original (WT) SARS-CoV-2 and cross-neutralization against B.1.351 (beta) variant carrying triple mutations of K417N, E484K, and N501Y. The results demonstrate that the use of favipiravir: (1) significantly accelerated the elimination of SARS-CoV-2 in the case vs. control groups (p = 0.027), (2) preserved the generation and persistence of neutralizing antibodies in the host, and (3) did not interfere the maturation of neutralizing potency of anti-SARS-CoV-2 and neutralizing breadth against SARS-CoV-2 variants. In conclusion, treatment of COVID-19 with favipiravir accelerates viral clearance and does not interfere the generation or maturation of neutralizing potency against both WT SARS-CoV-2 and its variants. Full article

(This article belongs to the Special Issue SARS-CoV-2 Innate and Adaptive Immune Responses)

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10 pages, 2176 KiB

Open AccessArticle

Expansion of CD56^dimCD16^neg NK Cell Subset and Increased Inhibitory KIRs in Hospitalized COVID-19 Patients

by José L. Casado, Elisa Moraga, Pilar Vizcarra, Héctor Velasco, Adrián Martín-Hondarza, Johannes Haemmerle, Sandra Gómez, Carmen Quereda and Alejandro Vallejo

Viruses 2022, 14(1), 46; https://doi.org/10.3390/v14010046 - 28 Dec 2021

Cited by 14 | Viewed by 3547

Abstract

Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2) infection induces elevated levels of inflammatory cytokines, which are mainly produced by the innate response to the virus. The role of NK cells, which are potent producers of IFN-γ and cytotoxicity, has not been sufficiently studied in [...] Read more.

Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2) infection induces elevated levels of inflammatory cytokines, which are mainly produced by the innate response to the virus. The role of NK cells, which are potent producers of IFN-γ and cytotoxicity, has not been sufficiently studied in the setting of SARS-CoV-2 infection. We confirmed a different distribution of NK cell subsets in hospitalized COVID-19 patients despite their NK cell deficiency. The impairment of this innate defense is mainly focused on the cytotoxic capacity of the CD56^dim NK cells. On the one hand, we found an expansion of the CD56^dimCD16^neg NK subset, lower cytotoxic capacities, and high frequencies of inhibitory 2DL1 and 2DL1/S1 KIR receptors in COVID-19 patients. On the other hand, the depletion of CD56^dimCD16^dim/bright NK cell subsets, high cytotoxic capacities, and high frequencies of inhibitory 2DL1 KIR receptors were found in COVID-19 patients. In contrast, no differences in the distribution of CD56^bright NK cell subsets were found in this study. These alterations in the distribution and phenotype of NK cells might enhance the impairment of this crucial innate line of defense during COVID-19 infection. Full article

(This article belongs to the Special Issue SARS-CoV-2 Innate and Adaptive Immune Responses)

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23 pages, 6748 KiB

Open AccessArticle

Single-Cell and Bulk RNASeq Profiling of COVID-19 Patients Reveal Immune and Inflammatory Mechanisms of Infection-Induced Organ Damage

by Alexandrea Bass, Yiran Liu and Sivanesan Dakshanamurthy

Viruses 2021, 13(12), 2418; https://doi.org/10.3390/v13122418 - 2 Dec 2021

Cited by 16 | Viewed by 4024

Abstract

The SARS-CoV-2 virus’s ability to induce hypercytokinemia and cause multiple organ failure makes it imperative to find effective treatments. To understand the mechanism of viral infection and its effects on organ tissues, we analyzed multiple single-cell and bulk RNAseq data from COVID-19 patients’ [...] Read more.

The SARS-CoV-2 virus’s ability to induce hypercytokinemia and cause multiple organ failure makes it imperative to find effective treatments. To understand the mechanism of viral infection and its effects on organ tissues, we analyzed multiple single-cell and bulk RNAseq data from COVID-19 patients’ organ samples. Various levels of severity of infection were accounted for, with comparative analyses between mild, moderate, and severely infected patients. Our analysis uncovered an upregulation of the innate immune response via several inflammatory genes, IL-2, IL-6, IL-8, IL-17A, and NF-κB. Consequently, we found that the upregulation of these downstream effects can lead to organ injury. The downregulated pathways such as eukaryotic initiation factor 2 (eIF2) and eIF4-mediated host translation, were found to lead to an increased viral translation. We also found that the loss of inhibitory peptides can suppress an overactive innate immune response via NF-κB and interleukin-mediated pathways. Investigation of viral-host protein mapping showed that the interaction of viral proteins with host proteins correlated with the down- and upregulation of host pathways such as decreased eIF2-mediated host translation and increased hypertrophy and fibrosis. Inflammation was increased via the stimulation of pro-inflammatory cytokines and suppression of host translation pathways that led to reduced inflammatory inhibitors. Cardiac hypertrophy and organ fibrosis were the results of increased inflammation in organs of severe and critical patients. Finally, we identified potential therapeutic targets for the treatment of COVID-19 and its deleterious effects on organs. Further experimental investigation would conclusively determine the effects of COVID-19 infection on organs other than the lungs and the effectiveness of the proposed therapeutic targets. Full article

(This article belongs to the Special Issue SARS-CoV-2 Innate and Adaptive Immune Responses)

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10 pages, 3125 KiB

Open AccessCommunication

Impairment of CD4+ T and Memory B Cell Responses but Normal Memory CD8+T-Cell Activation on Crohn’s Disease after COVID-19 Vaccination: A Twin Case

by Fabiana Gil Melgaço, Tamiris Azamor, Livia Melo Villar, Ana Paula Dinis Ano Bom and Juliana Gil Melgaço

Viruses 2021, 13(11), 2143; https://doi.org/10.3390/v13112143 - 24 Oct 2021

Cited by 4 | Viewed by 2542

Abstract

Vaccines to prevent the impact of SARS-CoV-2 are now available, including for patients with autoimmune diseases. However, there is no information about how inflammatory bowel disease (IBD) treatment could impact the cellular and humoral immune responses. This study evaluated SARS-CoV-2-specific humoral and cellular [...] Read more.

Vaccines to prevent the impact of SARS-CoV-2 are now available, including for patients with autoimmune diseases. However, there is no information about how inflammatory bowel disease (IBD) treatment could impact the cellular and humoral immune responses. This study evaluated SARS-CoV-2-specific humoral and cellular responses after vaccination with a two-dose schedule in a Crohn’s disease patient treated with Infliximab (10 mg/kg); we included comparisons with a monozygotic twin. The results showed that the Crohn’s disease’s twin (twin 2) had no antibody detection and reduced activation of CD4+ T cell responses, unlike the twin without the autoimmune disease (twin 1). Twin 2 developed antigen-specific central memory CD8+ T-cells and IFNγ production after the second dose of COVID-19 vaccination, similar to twin 1. These findings elucidated the role of T-cell immunity after COVID-19 immunization on IBD patients despite the lack of antibody production. Finally, our observation supports the consensus recommendation for IBD patients to receive COVID-19 vaccines. Full article

(This article belongs to the Special Issue SARS-CoV-2 Innate and Adaptive Immune Responses)

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12 pages, 1623 KiB

Open AccessArticle

Dynamic Assay for Profiling Anti-SARS-CoV-2 Antibodies and Their ACE2/Spike RBD Neutralization Capacity

by Thomas Phelan, Jean Dunne, Niall Conlon, Clíona Ní Cheallaigh, W. Mark Abbott, Raquel Faba-Rodriguez, Fatima Amanat, Florian Krammer, Mark A. Little, Gerry Hughes, Colm Bergin, Colm Kerr, Sudharshana Sundaresan, Aideen Long, William McCormack and Gareth Brady

Viruses 2021, 13(7), 1371; https://doi.org/10.3390/v13071371 - 15 Jul 2021

Cited by 13 | Viewed by 4538

Abstract

Serological assays have been widely employed during the coronavirus disease 2019 (COVID-19) pandemic to measure antibody responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and to track seroconversion in populations. However, currently available assays do not allow determination of neutralization capacity within [...] Read more.

Serological assays have been widely employed during the coronavirus disease 2019 (COVID-19) pandemic to measure antibody responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and to track seroconversion in populations. However, currently available assays do not allow determination of neutralization capacity within the assay protocol. Furthermore, commercial serology assays have a high buy-in cost that is inaccessible for many research groups. We have replicated the serological enzyme-linked immunosorbent assay for the detection of SARS-CoV-2 antibody isotypes, developed at the Icahn School of Medicine at Mount Sinai, New York. Additionally, we have modified the protocol to include a neutralization assay with only a minor modification to this protocol. We used this assay to screen local COVID-19 patient sera (n = 91) and pre-COVID-19 control sera (n = 103), and obtained approximate parity with approved commercial anti-nucleoprotein-based assays with these sera. Furthermore, data from our neutralization assay closely aligns with that generated using a spike-based pseudovirus infection model when a subset of patient sera was analyzed. Full article

(This article belongs to the Special Issue SARS-CoV-2 Innate and Adaptive Immune Responses)

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Review

Jump to: Editorial, Research

19 pages, 1805 KiB

Open AccessReview

Coronaviral Infection and Interferon Response: The Virus-Host Arms Race and COVID-19

by Qi Liu, Sensen Chi, Kostyantyn Dmytruk, Olena Dmytruk and Shuai Tan

Viruses 2022, 14(7), 1349; https://doi.org/10.3390/v14071349 - 21 Jun 2022

Cited by 10 | Viewed by 3254

Abstract

The recent pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in unprecedented morbidity and mortality worldwide. The host cells use a number of pattern recognition receptors (PRRs) for early detection of coronavirus infection, and timely interferon secretion is highly [...] Read more.

The recent pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in unprecedented morbidity and mortality worldwide. The host cells use a number of pattern recognition receptors (PRRs) for early detection of coronavirus infection, and timely interferon secretion is highly effective against SARS-CoV-2 infection. However, the virus has developed many strategies to delay interferon secretion and disarm cellular defense by intervening in interferon-associated signaling pathways on multiple levels. As a result, some COVID-19 patients suffered dramatic susceptibility to SARS-CoV-2 infection, while another part of the population showed only mild or no symptoms. One hypothesis suggests that functional differences in innate immune integrity could be the key to such variability. This review tries to decipher possible interactions between SARS-CoV-2 proteins and human antiviral interferon sensors. We found that SARS-CoV-2 actively interacts with PRR sensors and antiviral pathways by avoiding interferon suppression, which could result in severe COVID-19 pathogenesis. Finally, we summarize data on available antiviral pharmaceutical options that have shown potential to reduce COVID-19 morbidity and mortality in recent clinical trials. Full article

(This article belongs to the Special Issue SARS-CoV-2 Innate and Adaptive Immune Responses)

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17 pages, 1949 KiB

Open AccessReview

Innate and Adaptive Immune Responses in the Upper Respiratory Tract and the Infectivity of SARS-CoV-2

by Ranjan Ramasamy

Viruses 2022, 14(5), 933; https://doi.org/10.3390/v14050933 - 29 Apr 2022

Cited by 14 | Viewed by 7139

Abstract

Increasing evidence shows the nasal epithelium to be the initial site of SARS-CoV-2 infection, and that early and effective immune responses in the upper respiratory tract (URT) limit and eliminate the infection in the URT, thereby preventing infection of the lower respiratory tract [...] Read more.

Increasing evidence shows the nasal epithelium to be the initial site of SARS-CoV-2 infection, and that early and effective immune responses in the upper respiratory tract (URT) limit and eliminate the infection in the URT, thereby preventing infection of the lower respiratory tract and the development of severe COVID-19. SARS-CoV-2 interferes with innate immunity signaling and evolves mutants that can reduce antibody-mediated immunity in the URT. Recent genetic and immunological advances in understanding innate immunity to SARS-CoV-2 in the URT, and the ability of prior infections as well as currently available injectable and potential intranasal COVID-19 vaccines to generate anamnestic adaptive immunity in the URT, are reviewed. It is suggested that the more detailed investigation of URT immune responses to all types of COVID-19 vaccines, and the development of safe and effective COVID-19 vaccines for intranasal administration, are important needs. Full article

(This article belongs to the Special Issue SARS-CoV-2 Innate and Adaptive Immune Responses)

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21 pages, 3042 KiB

Open AccessReview

Severe Acute Respiratory Syndrome Coronavirus 2 Variants of Concern: A Perspective for Emerging More Transmissible and Vaccine-Resistant Strains

by Anacleto Silva de Souza, Vitor Martins de Freitas Amorim, Gabriela D. A. Guardia, Filipe F. dos Santos, Henning Ulrich, Pedro A. F. Galante, Robson Francisco de Souza and Cristiane Rodrigues Guzzo

Viruses 2022, 14(4), 827; https://doi.org/10.3390/v14040827 - 16 Apr 2022

Cited by 19 | Viewed by 7917

Abstract

Novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOC) are constantly threatening global public health. With no end date, the pandemic persists with the emergence of novel variants that threaten the effectiveness of diagnostic tests and vaccines. Mutations in the [...] Read more.

Novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOC) are constantly threatening global public health. With no end date, the pandemic persists with the emergence of novel variants that threaten the effectiveness of diagnostic tests and vaccines. Mutations in the Spike surface protein of the virus are regularly observed in the new variants, potentializing the emergence of novel viruses with different tropism from the current ones, which may change the severity and symptoms of the disease. Growing evidence has shown that mutations are being selected in favor of variants that are more capable of evading the action of neutralizing antibodies. In this context, the most important factor guiding the evolution of SARS-CoV-2 is its interaction with the host’s immune system. Thus, as current vaccines cannot block the transmission of the virus, measures complementary to vaccination, such as the use of masks, hand hygiene, and keeping environments ventilated remain essential to delay the emergence of new variants. Importantly, in addition to the involvement of the immune system in the evolution of the virus, we highlight several chemical parameters that influence the molecular interactions between viruses and host cells during invasion and are also critical tools making novel variants more transmissible. In this review, we dissect the impacts of the Spike mutations on biological parameters such as (1) the increase in Spike binding affinity to hACE2; (2) bound time for the receptor to be cleaved by the proteases; (3) how mutations associate with the increase in RBD up-conformation state in the Spike ectodomain; (4) expansion of uncleaved Spike protein in the virion particles; (5) increment in Spike concentration per virion particles; and (6) evasion of the immune system. These factors play key roles in the fast spreading of SARS-CoV-2 variants of concern, including the Omicron. Full article

(This article belongs to the Special Issue SARS-CoV-2 Innate and Adaptive Immune Responses)

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13 pages, 1250 KiB

Open AccessReview

An Update on Innate Immune Responses during SARS-CoV-2 Infection

by Yu Zhang, Shuaiyin Chen, Yuefei Jin, Wangquan Ji, Weiguo Zhang and Guangcai Duan

Viruses 2021, 13(10), 2060; https://doi.org/10.3390/v13102060 - 14 Oct 2021

Cited by 11 | Viewed by 3388

Abstract

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a member of the Coronaviridae family, which is responsible for the COVID-19 pandemic followed by unprecedented global societal and economic disruptive impact. The innate immune system is the body’s first line of defense against [...] Read more.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a member of the Coronaviridae family, which is responsible for the COVID-19 pandemic followed by unprecedented global societal and economic disruptive impact. The innate immune system is the body’s first line of defense against invading pathogens and is induced by a variety of cellular receptors that sense viral components. However, various strategies are exploited by SARS-CoV-2 to disrupt the antiviral innate immune responses. Innate immune dysfunction is characterized by the weak generation of type I interferons (IFNs) and the hypersecretion of pro-inflammatory cytokines, leading to mortality and organ injury in patients with COVID-19. This review summarizes the existing understanding of the mutual effects between SARS-CoV-2 and the type I IFN (IFN-α/β) responses, emphasizing the relationship between host innate immune signaling and viral proteases with an insight on tackling potential therapeutic targets. Full article

(This article belongs to the Special Issue SARS-CoV-2 Innate and Adaptive Immune Responses)

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