Linkage of Lambda Interferons in Protection Against Severe COVID-19

Shahbazi, Mehdi; Maleh, Parviz Amri; Bagherzadeh, Mojgan; Moulana, Zahra; Sepidarkish, Mahdi; Rezanejad, Maryam; Mirzakhani, Mohammad; Ebrahimpour, Soheil; Ghorbani, Hossein; Ahmadnia, Zahra; Javanian, Mostafa; Bayani, Masomeh; Mohammadnia‐Afrouzi, Mousa

doi:10.1089/jir.2020.0187

Cited by 16 publications

(13 citation statements)

References 19 publications

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“…In our previous articles, we assessed some immunological features of moderate/severe and critical COVID-19 patients with interesting results. We showed that non-intensive care unit (ICU) patients had a significantly higher amount of interferon λ1 (IFN-λ1) (836.7 ± 284.6 vs. 81.57 ± 34.25) and INF-λ2 (798.8 ± 301.5 vs. 48.32 ± 28.13) compared with ICU patients [ 15 ]. The INF-λ family or type III interferon is the most recently discovered interferon and divide into 4 members, including IFN-λ1/IL-29, IFN-λ2/IL-28 A, IFN-λ3/IL-28 B, and IFN-λ4.…”

Section: Discussionmentioning

confidence: 99%

“…The INF-λ family or type III interferon is the most recently discovered interferon and divide into 4 members, including IFN-λ1/IL-29, IFN-λ2/IL-28 A, IFN-λ3/IL-28 B, and IFN-λ4. INF-λ receptor 1 (INF-λR1) and IL-10R2 are the heterodimeric receptors of INF-λ [ 15 ]. Since the expression of INF-λR1 is primarily limited to the respiratory tract epithelial cells, INF-λ has a major role in mucosal immunity and viral respiratory tract infection [ [15] , [16] , [17] ].…”

Section: Discussionmentioning

confidence: 99%

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The association of decreased HLA-G+ immune cell frequencies with critical COVID-19 patients

Ramzannezhad

Tarighi

Dnia-Afrouzi

et al. 2022

Microbial Pathogenesis

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

The association of decreased HLA-G+ immune cell frequencies with critical COVID-19 patients

Ramzannezhad

Tarighi

Dnia-Afrouzi

et al. 2022

Microbial Pathogenesis

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“…Viroporins localized in the subcellular membranes of these lung airway epithelial cells is the primary cause of ionic imbalance and thus can be potential therapeutic targets against ARDS, which is the primary reason for fatality in SARS-CoV-2 infection [72,73]. Transcriptomics analysis from patient samples affected with SARS-CoV-2 showed an upregulation in inflammatory response mediated by several interleukins and interferons [74] which are probably regulated by NFкB [75]. Increase in CD40 [76], IL-6 [77], IL-12 [78] and IL-33 [79] transcripts strongly correlate with similar expression patterns of differentially expressed genes in Acute Lung Injury, ARDS and pulmonary fibrosis.…”

Section: Discussionmentioning

confidence: 99%

SARS- CoV-2 viroporins: A multi-omics insight from nucleotides to amino acids

Sarkar¹,

Etheimer

Saha³

2021

Preprint

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COVID-19 is caused by SARS-CoV-2 which has affected nearly 220 million people worldwide and death toll close to 5 million as of present day. The approved vaccines are lifesaving yet temporary solutions to such a devastating pandemic. Viroporins are important players of the viral life cycle of SARS-Cov-2 and one of the primary determinants of its pathogenesis. We studied the two prominent viroporins of SARS-CoV-2 (i) Orf3a and (ii) Envelope (E) protein from a structural point of view. Orf3a has several hotspots of mutations which has been reported in SARS-CoV-2 with respect to SARS-CoV-1. Mutations in SARS-CoV-2 Orf3a channel forming residues enhances the formation of a prominent the inter-subunit channel, which was not present in the SARS-CoV-1 Orf3a. This enhanced structural feature can be correlated with higher channelling activity in SARS-CoV-2 than in SARS-CoV-1. On the other hand, E protein is one of the most conserved protein among the SARS-CoV proteome. We found that the water molecules form networks of electrostatic interactions with the polar residues in the E protein putative wetted condition while no water channel formation was observed in the putative dewetted condition. This aqueous medium mediates the non-selective translocation of cations thus affecting the ionic homeostasis of the host cellular compartments. This ionic imbalance leads to increased inflammatory response in the host cell. Our results shed light into the mechanism of viroporin action, which can be leveraged for the development of antiviral therapeutics. Furthermore, our results corroborate with previously published transcriptomic data from COVID-19 infected lung alveolar cells where inflammatory responses and molecular regulators directly impacted by ion channelling were upregulated. These observations overlap with transcript upregulation observed in diseases having acute lung injury, pulmonary fibrosis and Acute Respiratory Distress Syndrome (ARDS).

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“…Similarly, in mice, the administration of pegylated (PEG)-IFN-λ1a diminished SARS-CoV-2 replication [ 114 ]. Interestingly, in observational studies, increased IFN-λ1 and IFN-λ2 levels in serum were associated with a better prognosis [ 115 , 116 ]. Based on these data, clinical trials have begun to evaluate the effect of PEG-IFN-λ1a therapy in COVID19 patients, which have shown contradictory results.…”

Section: Therapeutics Targeting Innate Immune Systemmentioning

confidence: 99%

Escape and Over-Activation of Innate Immune Responses by SARS-CoV-2: Two Faces of a Coin

Mattoo

Kim

Ahn

et al. 2022

Viruses

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In the past 20 years, coronaviruses (CoVs), including SARS-CoV-1, MERS-CoV, and SARS-CoV-2, have rapidly evolved and emerged in the human population. The innate immune system is the first line of defense against invading pathogens. Multiple host cellular receptors can trigger the innate immune system to eliminate invading pathogens. However, these CoVs have acquired strategies to evade innate immune responses by avoiding recognition by host sensors, leading to impaired interferon (IFN) production and antagonizing of the IFN signaling pathways. In contrast, the dysregulated induction of inflammasomes, leading to uncontrolled production of IL-1 family cytokines (IL-1β and IL-18) and pyroptosis, has been associated with COVID-19 pathogenesis. This review summarizes innate immune evasion strategies employed by SARS-CoV-1 and MERS-CoV in brief and SARS-CoV-2 in more detail. In addition, we outline potential mechanisms of inflammasome activation and evasion and their impact on disease prognosis.

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Linkage of Lambda Interferons in Protection Against Severe COVID-19

Cited by 16 publications

References 19 publications

The association of decreased HLA-G+ immune cell frequencies with critical COVID-19 patients

The association of decreased HLA-G+ immune cell frequencies with critical COVID-19 patients

SARS- CoV-2 viroporins: A multi-omics insight from nucleotides to amino acids

Escape and Over-Activation of Innate Immune Responses by SARS-CoV-2: Two Faces of a Coin

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