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Open AccessEditorial

Special Issue “Viral-Induced Inflammation”

by Simone de Araújo, Luciana P. Tavares and Vivian Vasconcelos Costa

Viruses 2024, 16(4), 588; https://doi.org/10.3390/v16040588 - 11 Apr 2024

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Abstract

Inflammation is a protective host response essential for controlling viral replication and promoting tissue repair [...] Full article

(This article belongs to the Special Issue Viral-Induced Inflammation)

Research

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17 pages, 2898 KiB

Open AccessArticle

Dietary Vitamin D Mitigates Coronavirus-Induced Lung Inflammation and Damage in Mice

by Gabriel Campolina-Silva, Ana Cláudia dos Santos Pereira Andrade, Manoela Couto, Paloma G. Bittencourt-Silva, Celso M. Queiroz-Junior, Larisse de Souza B. Lacerda, Ian de Meira Chaves, Leonardo C. de Oliveira, Fernanda Martins Marim, Cleida A. Oliveira, Glauber S. F. da Silva, Mauro Martins Teixeira and Vivian Vasconcelos Costa

Viruses 2023, 15(12), 2434; https://doi.org/10.3390/v15122434 - 15 Dec 2023

Cited by 3 | Viewed by 2113

Abstract

The COVID-19 pandemic caused by the SARS-CoV-2 (β-CoV) betacoronavirus has posed a significant threat to global health. Despite the availability of vaccines, the virus continues to spread, and there is a need for alternative strategies to alleviate its impact. Vitamin D, a secosteroid [...] Read more.

The COVID-19 pandemic caused by the SARS-CoV-2 (β-CoV) betacoronavirus has posed a significant threat to global health. Despite the availability of vaccines, the virus continues to spread, and there is a need for alternative strategies to alleviate its impact. Vitamin D, a secosteroid hormone best known for its role in bone health, exhibits immunomodulatory effects in certain viral infections. Here, we have shown that bioactive vitamin D (calcitriol) limits in vitro replication of SARS-CoV-2 and murine coronaviruses MHV-3 and MHV-A59. Comparative studies involving wild-type mice intranasally infected with MHV-3, a model for studying β-CoV respiratory infections, confirmed the protective effect of vitamin D in vivo. Accordingly, mice fed a standard diet rapidly succumbed to MHV-3 infection, whereas those on a vitamin D-rich diet (10,000 IU of Vitamin D₃/kg) displayed increased resistance to acute respiratory damage and systemic complications. Consistent with these findings, the vitamin D-supplemented group exhibited lower viral titers in their lungs and reduced levels of TNF, IL-6, IL-1β, and IFN-γ, alongside an enhanced type I interferon response. Altogether, our findings suggest vitamin D supplementation ameliorates β-CoV-triggered respiratory illness and systemic complications in mice, likely via modulation of the host’s immune response to the virus. Full article

(This article belongs to the Special Issue Viral-Induced Inflammation)

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18 pages, 21904 KiB

Open AccessArticle

A 5-Lipoxygenase Inhibitor, Zileuton, Modulates Host Immune Responses and Improves Lung Function in a Model of Severe Acute Respiratory Syndrome (SARS) Induced by Betacoronavirus

by Rafaela das Dores Pereira, Rayane Aparecida Nonato Rabelo, Natália Fernanda de Melo Oliveira, Samuel Luiz Teixeira Porto, Ana Claudia dos Santos Pereira Andrade, Celso M. Queiroz-Junior, César Luís Nascimento Barbosa, Luiz Pedro de Souza-Costa, Felipe Rocha da Silva Santos, Fernando Bento Rodrigues Oliveira, Bárbara Luísa Vieira da Silva, Hanna L. Umezu, Raquel Ferreira, Glauber S. F. da Silva, Jader Santos Cruz, Mauro Martins Teixeira, Vivian Vasconcelos Costa and Fabiana Simão Machado

Viruses 2023, 15(10), 2049; https://doi.org/10.3390/v15102049 - 4 Oct 2023

Cited by 2 | Viewed by 1929

Abstract

Exacerbated inflammatory responses are a hallmark of severe coronavirus disease 2019 (COVID-19). Zileuton (Zi) is a selective inhibitor of 5-lipoxygenase, an enzyme involved in the production of several inflammatory/pro-resolving lipid mediators. Herein, we investigated the effect of Zi treatment in a severe acute [...] Read more.

Exacerbated inflammatory responses are a hallmark of severe coronavirus disease 2019 (COVID-19). Zileuton (Zi) is a selective inhibitor of 5-lipoxygenase, an enzyme involved in the production of several inflammatory/pro-resolving lipid mediators. Herein, we investigated the effect of Zi treatment in a severe acute respiratory syndrome (SARS) model. Mouse hepatitis virus (MHV)3-infected mice treated with Zi significantly improved the clinical score, weight loss, cardiopulmonary function, and survival rates compared with infected untreated animals. The protection observed in Zi-treated mice was associated with a lower inflammatory score, reduced dendritic cell-producing tumor necrosis factor (TNF), and increased neutrophil-producing interleukin (IL)-10 in the lungs three days after infection (dpi). At 5 dpi, the lungs of treated mice showed an increase in Th2-, Treg CD4⁺-, and Treg CD8⁺-producing IL-10 and reduced Th1 infiltrating cells. Furthermore, similar results were found upon Zi treatment after SARS-CoV-2 infection in transgenic mice expressing the human angiotensin I-converting enzyme 2 (ACE2) receptor driven by the cytokeratin-18 (K18) gene promoter (K18-hACE2), significantly improving the clinical score, weight loss, and lung inflammatory score compared with untreated animals. Our data suggest that Zi protects against developing severe lung disease during SARS induced by betacoronavirus without affecting the host’s capacity to deal with infection. Full article

(This article belongs to the Special Issue Viral-Induced Inflammation)

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18 pages, 2567 KiB

Open AccessArticle

Enhancement of IL-6 Production Induced by SARS-CoV-2 Nucleocapsid Protein and Bangladeshi COVID-19 Patients’ Sera

by Abu Hasan, Rummana Rahim, Emi E. Nakayama, Kazuko Uno, Nazmul Hasan, Mizanur Rahman and Tatsuo Shioda

Viruses 2023, 15(10), 2018; https://doi.org/10.3390/v15102018 - 28 Sep 2023

Cited by 4 | Viewed by 3023

Abstract

Coronavirus disease 2019 (COVID-19) is a respiratory tract infection caused by severe acute respiratory syndrome coronavirus 2 that can have detrimental effects on multiple organs and accelerate patient mortality. This study, which encompassed 130 confirmed COVID-19 patients who were assessed at three different [...] Read more.

Coronavirus disease 2019 (COVID-19) is a respiratory tract infection caused by severe acute respiratory syndrome coronavirus 2 that can have detrimental effects on multiple organs and accelerate patient mortality. This study, which encompassed 130 confirmed COVID-19 patients who were assessed at three different time points (i.e., 3, 7, and 12 days) after the onset of symptoms, investigated interleukin-6 (IL-6) enhancement induced by a viral nucleocapsid (N) protein from a myeloid cell line. Disease severity was categorized as mild, moderate, or severe. The severe cases were characterized as having significant elevations in serum IL-6, C-reactive protein, D-dimer, ferritin, creatinine, leukocytes, and neutrophil-to-lymphocyte ratio and decreased hemoglobin, hematocrit, and albumin levels compared with mild and moderate cases. To evaluate IL-6-inducing activity, heat-inactivated sera from these patients were incubated with and without the N protein. The findings showed a progressive increase in IL-6 production in severe cases upon N protein stimulation. There was a strong correlation between anti-N antibodies and levels of IL-6 secreted by myeloid cells in the presence of N protein and sera, indicating the crucial role that the anti-N antibody plays in inducing IL-6 production. Uncontrolled IL-6 production played a pivotal role in disease pathogenesis, exacerbating both disease severity and mortality. Efficiently targeting the N protein could potentially be employed as a therapeutic strategy for regulating the immune response and alleviating inflammation in severe cases. Full article

(This article belongs to the Special Issue Viral-Induced Inflammation)

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14 pages, 3239 KiB

Open AccessArticle

Compartmentalized Regulation of Pulmonary and Systemic Inflammation in Critical COVID-19 Patients

by Luciana Santiago, Marcela Helena Gonçalves-Pereira, Mariana Sousa Vieira, Cecilia Gómez Ravetti, Paula Frizera Vassallo, Rafael Silva e Castro, Pedro Pires Costa Pimenta, Marcus Vinícius Melo de Andrade, Helton da Costa Santiago and Vandack Nobre

Viruses 2023, 15(8), 1704; https://doi.org/10.3390/v15081704 - 8 Aug 2023

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Abstract

Critical COVID-19 has been associated with altered patterns of cytokines. Distinct inflammatory processes in systemic and pulmonary sites have been reported, but studies comparing these two sites are still scarce. We aimed to evaluate the profile of pulmonary and systemic cytokines and chemokines [...] Read more.

Critical COVID-19 has been associated with altered patterns of cytokines. Distinct inflammatory processes in systemic and pulmonary sites have been reported, but studies comparing these two sites are still scarce. We aimed to evaluate the profile of pulmonary and systemic cytokines and chemokines in critically ill COVID-19 patients. Levels of cytokines and chemokines were measured in plasma samples and minibronchoalveolar lavage of critical COVID-19 patients within 48 h and 5–8 days after intubation. Distinct inflammatory processes were observed in the lungs and blood, which were regulated separately. Survivor patients showed higher lung cytokine levels including IFN-γ, IL-2, IL-4, G-CSF, and CCL4, while nonsurvivors displayed higher levels in the blood, which included IL-6, CXCL8, CXCL10, CCL2, and CCL4. Furthermore, our findings indicate that high TNF and CXCL8 levels in the mini-BAL were associated with better lung oxygen exchange capacity, whereas high levels of IFN-γ in plasma were associated with worse lung function, as measured using the PaO₂/FiO₂ ratio. These results suggest that a robust and localized inflammatory response in the lungs is protective and associated with survival, whereas a systemic inflammatory response is detrimental and associated with mortality in critical COVID-19. Full article

(This article belongs to the Special Issue Viral-Induced Inflammation)

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21 pages, 5770 KiB

Open AccessArticle

Tumour Necrosis Factor-α, Chemokines, and Leukocyte Infiltrate Are Biomarkers for Pathology in the Brains of Venezuelan Equine Encephalitis (VEEV)-Infected Mice

by Amanda L. Phelps, Francisco J. Salguero, Laura Hunter, Alexander L. Stoll, Dominic C. Jenner, Lyn M. O’Brien, E. Diane Williamson, M. Stephen Lever and Thomas R. Laws

Viruses 2023, 15(6), 1307; https://doi.org/10.3390/v15061307 - 31 May 2023

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Abstract

Venezuelan equine encephalitis virus (VEEV) is a disease typically confined to South and Central America, whereby human disease is characterised by a transient systemic infection and occasionally severe encephalitis, which is associated with lethality. Using an established mouse model of VEEV infection, the [...] Read more.

Venezuelan equine encephalitis virus (VEEV) is a disease typically confined to South and Central America, whereby human disease is characterised by a transient systemic infection and occasionally severe encephalitis, which is associated with lethality. Using an established mouse model of VEEV infection, the encephalitic aspects of the disease were analysed to identify biomarkers associated with inflammation. Sequential sampling of lethally challenged mice (infected subcutaneously) confirmed a rapid onset systemic infection with subsequent spread to the brain within 24 h of the challenge. Changes in inflammatory biomarkers (TNF-α, CCL-2, and CCL-5) and CD45⁺ cell counts were found to correlate strongly to pathology (

R > 0.9

) and present previously unproven biomarkers for disease severity in the model, more so than viral titre. The greatest level of pathology was observed within the olfactory bulb and midbrain/thalamus. The virus was distributed throughout the brain/encephalon, often in areas not associated with pathology. The principal component analysis identified five principal factors across two independent experiments, with the first two describing almost half of the data: (1) confirmation of a systemic Th1-biased inflammatory response to VEEV infection, and (2) a clear correlation between specific inflammation of the brain and clinical signs of disease. Targeting strongly associated biomarkers of deleterious inflammation may ameliorate or even eliminate the encephalitic syndrome of this disease. Full article

(This article belongs to the Special Issue Viral-Induced Inflammation)

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22 pages, 4547 KiB

Open AccessArticle

ZIKV Strains Elicit Different Inflammatory and Anti-Viral Responses in Microglia Cells

by Fernanda Bellaniza Caminha de Oliveira, Vanessa Paola Alves Sampaio de Sá Freire, Sharton Vinicius Antunes Coelho, Lana Monteiro Meuren, Julys da Fonseca Palmeira, Ana Luísa Cardoso, Francisco de Assis Rocha Neves, Bergmann Morais Ribeiro, Gustavo Adolfo Argañaraz, Luciana Barros de Arruda and Enrique Roberto Argañaraz

Viruses 2023, 15(6), 1250; https://doi.org/10.3390/v15061250 - 26 May 2023

Cited by 6 | Viewed by 2074

Abstract

In recent years, the Zika Virus (ZIKV) has caused pandemic outbreaks associated with a high rate of congenital ZIKV syndrome (CZS). Although all strains associated with worldwide outbreaks derive from the Asian lineage, the reasons for their enhanced spread and severity are not [...] Read more.

In recent years, the Zika Virus (ZIKV) has caused pandemic outbreaks associated with a high rate of congenital ZIKV syndrome (CZS). Although all strains associated with worldwide outbreaks derive from the Asian lineage, the reasons for their enhanced spread and severity are not fully understood. In this study, we conducted a comparative analysis of miRNAs (miRNA-155/146a/124) and their cellular targets (SOCS1/3, SHP1, TRAF6, IRAK1), as well as pro- and anti-inflammatory and anti-viral cytokines (IL-6, TNF-α, IFN-γ, IL-10, and IFN-β) and peroxisome proliferator-activated receptor γ (PPAR-γ) expression in BV2 microglia cells infected with ZIKV strains derived from African and Asian lineages (ZIKV_MR766 and ZIKV_PE243). BV2 cells were susceptible to both ZIKV strains, and showed discrete levels of viral replication, with delayed release of viral particles without inducing significant cytopathogenic effects. However, the ZIKV_MR766 strain showed higher infectivity and replicative capacity, inducing a higher expression of microglial activation markers than the ZIKV_PE243 strain. Moreover, infection with the ZIKV_MR766 strain promoted both a higher inflammatory response and a lower expression of anti-viral factors compared to the ZIKV_PE243 strain. Remarkably, the ZIKK_PE243 strain induced significantly higher levels of the anti-inflammatory nuclear receptor—PPAR-γ. These findings improve our understanding of ZIKV-mediated modulation of inflammatory and anti-viral innate immune responses and open a new avenue to explore underlining mechanisms involved in the pathogenesis of ZIKV-associated diseases. Full article

(This article belongs to the Special Issue Viral-Induced Inflammation)

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Review

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Open AccessReview

The Functional Roles of MDSCs in Severe COVID-19 Pathogenesis

by Jia Soon Len, Clara W. T. Koh and Kuan Rong Chan

Viruses 2024, 16(1), 27; https://doi.org/10.3390/v16010027 - 23 Dec 2023

Cited by 4 | Viewed by 1939

Abstract

Severe COVID-19 is a major cause of morbidity and mortality worldwide, especially among those with co-morbidities, the elderly, and the immunocompromised. However, the molecular determinants critical for severe COVID-19 progression remain to be fully elucidated. Meta-analyses of transcriptomic RNAseq and single-cell sequencing datasets [...] Read more.

Severe COVID-19 is a major cause of morbidity and mortality worldwide, especially among those with co-morbidities, the elderly, and the immunocompromised. However, the molecular determinants critical for severe COVID-19 progression remain to be fully elucidated. Meta-analyses of transcriptomic RNAseq and single-cell sequencing datasets comparing severe and mild COVID-19 patients have demonstrated that the early expansion of myeloid-derived suppressor cells (MDSCs) could be a key feature of severe COVID-19 progression. Besides serving as potential early prognostic biomarkers for severe COVID-19 progression, several studies have also indicated the functional roles of MDSCs in severe COVID-19 pathogenesis and possibly even long COVID. Given the potential links between MDSCs and severe COVID-19, we examine the existing literature summarizing the characteristics of MDSCs, provide evidence of MDSCs in facilitating severe COVID-19 pathogenesis, and discuss the potential therapeutic avenues that can be explored to reduce the risk and burden of severe COVID-19. We also provide a web app where users can visualize the temporal changes in specific genes or MDSC-related gene sets during severe COVID-19 progression and disease resolution, based on our previous study. Full article

(This article belongs to the Special Issue Viral-Induced Inflammation)

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