Roles and functions of SARS-CoV-2 proteins in host immune evasion

Rashid, Farooq; Xie, Zhixun; Suleman, Muhammad; Shah, Abdullah; Khan, Suliman; Luo, Sisi

doi:10.3389/fimmu.2022.940756

Cited by 77 publications

(65 citation statements)

References 91 publications

(189 reference statements)

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“…Higher ISGs responses in blood during week 1 among severe COVID-19 patients is consistent with an early circulation of activated myeloid cells (monocytes and neutrophils) that are subsequently recruited to the lungs of severe patients. Lower ISGs responses in the URT compared with blood, despite higher IFN expression in the URT, is consistent with impaired IFN signaling in SARS-CoV-2 infected nasopharyngeal epithelium among severe patients through host and viral factors that directly suppress ISGs and the IFN response (38,39). These findings are consistent with observations from prior studies (26).…”

Section: Discussionsupporting

confidence: 88%

Antiviral innate immunity is diminished in the upper respiratory tract of severe COVID-19 patients

Ramos‐Benitez

Strich

Alehashemi

et al. 2022

Preprint

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Understanding early innate immune responses to coronavirus disease 2019 (COVID‐19) is crucial to developing targeted therapies to mitigate disease severity. Severe acute respiratory syndrome coronavirus (SARS-CoV)-2 infection elicits interferon expression leading to transcription of IFN-stimulated genes (ISGs) to control viral replication and spread. SARS-CoV-2 infection also elicits NF-κB signaling which regulates inflammatory cytokine expression contributing to viral control and likely disease severity. Few studies have simultaneously characterized these two components of innate immunity to COVID-19. We designed a study to characterize the expression of interferon alpha-2 (IFNA2) and interferon beta-1 (IFNB1), both type-1 interferons (IFN-1), interferon-gamma (IFNG), a type-2 interferon (IFN-2), ISGs, and NF-κB response genes in the upper respiratory tract (URT) of patients with mild (outpatient) versus severe (hospitalized) COVID-19. Further, we characterized the weekly dynamics of these responses in the upper and lower respiratory tracts (LRTs) and blood of severe patients to evaluate for compartmental differences. We observed significantly increased ISG and NF-κB responses in the URT of mild compared with severe patients early during illness. This pattern was associated with increased IFNA2 and IFNG expression in the URT of mild patients, a trend toward increased IFNB1-expression and significantly increased STING/IRF3/cGAS expression in the URT of severe patients. Our by-week across-compartment analysis in severe patients revealed significantly higher ISG responses in the blood compared with the URT and LRT of these patients during the first week of illness, despite significantly lower expression of IFNA2, IFNB1, and IFNG in blood. NF-κB responses, however, were significantly elevated in the LRT compared with the URT and blood of severe patients during peak illness (week 2). Our data support that severe COVID-19 is associated with impaired interferon signaling in the URT during early illness and robust pro-inflammatory responses in the LRT during peak illness.

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Section: Discussionsupporting

confidence: 88%

Antiviral innate immunity is diminished in the upper respiratory tract of severe COVID-19 patients

Ramos‐Benitez

Strich

Alehashemi

et al. 2022

Preprint

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“…This may be due to the adaptation of multiple immunosuppression strategies by the SARS‐CoV‐2 during different phases of infection. Moreover, delayed and constitutive IFN expression and insufficient host IFN responses are probably due to the inhibition of IFN signaling by viral ORF6 and ORF9b proteins since SARS‐CoV‐2 patients undergo immunosuppression by viral evasion by distinct mechanisms as they interfere with host innate antiviral immunity in multiple ways such as innate sensing, IFN production, IFN signaling, and interferon‐stimulated gene effector functions 9–12 …”

mentioning

confidence: 99%

Molecular insights into onset of autoimmunity in SARS‐CoV‐2 infected patients

Laxminarayana¹

2022

Rheumatology & Autoimmunity

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Some of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infected patients are facing long-term devastating effects like induction of autoimmune diseases. Here, I discuss molecular mechanisms and risk factors involved in the induction of autoimmune diseases after SARS-CoV-2 infections. Transcript editing genes were upregulated during SARS-CoV-2 infections, which might have edited host gene transcripts and paved the way for autoantigens generation and presented as nonself to generate autoantibodies followed by auto immunogenicity after SARS-CoV-2 infections. Therefore, some SARS-CoV-2 patients acquire autoimmunity. The transient and/or innocuous autoimmune response in some SARS-CoV-2 infected patients may be due to a lack of repeated production of autoantibodies to host autoantigens and/or viral antigens, which are needed to boost autoimmune response. In the future, SARS-CoV-2 mediated autoimmune disease onset will be a challenging task. Therefore, possible preventive measures and strategies to minimize and/or preclude such SARS-CoV-2 mediated autoimmune diseases have been presented in this commentary.

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“…ORF3a, ORF7a, and ORF8 are accessory proteins of CoVs that exhibit high variability. The accessory proteins do not play a role in viral replication but have an important role in host immune evasion ( 50 , 51 ). The innate interferon (IFN) response constitutes one of the host's first lines of defense against viral infection.…”

Section: Discussionmentioning

confidence: 99%

Clinical features and effectiveness of Chinese medicine in patients with COVID-19 from overseas: A retrospective study in Xiamen, China

Huang

Li²,

Li³

et al. 2022

Front. Public Health

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COVID-19, referred to as new coronary pneumonia, is an acute infectious disease caused by a new type of coronavirus SARS-CoV-2. To evaluate the effect of integrated Chinese medicine and Western medicine in patients with COVID-19 from overseas. Data were collected from 178 COVID-19 patients overseas at First Affiliated Hospital of Xiamen University from April 1, 2021 to July 31, 2021. These patients received therapy of integrated Chinese medicine and western medicine. Demographic data and clinical characteristics were extracted and analyzed. In addition, the prescription which induced less length of PCR positive days and hospitalization days than the median value was obtained. The top 4 frequently used Chinese medicine and virus-related genes were analyzed by network pharmacology and bioinformatics analysis. According to the chest computed tomography (CT) measurement, abnormal lung findings were observed in 145 subjects. The median length of positive PCR/hospitalization days was 7/7 days for asymptomatic subjects, 14/24 days for mild subjects, 10/15 days for moderate subjects, and 14/20 days for severe subjects. The most frequently used Chinese medicine were Scutellaria baicalensis (Huangqin), Glycyrrhiza uralensis (Gancao), Bupleurum chinense (Chaihu), and Pinellia ternata (Banxia). The putative active ingredients were baicalin, stigmasterol, sigmoidin-B, cubebin, and troxerutin. ACE, SARS-CoV-2 3CL, SARS-CoV-2 Spike, SARS-CoV-2 ORF7a, and caspase-6 showed good binding properties to active ingredients. In conclusion, the clinical results showed that integrated Chinese medicine and Western medicine are effective in treating COVID-19 patients from overseas. Based on the clinical outcomes, the putative ingredients from Chinese medicine and the potential targets of SARS-CoV-2 were provided, which could provide a reference for the clinical application of Chinese medicine in treating COVID-19 worldwide.

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Roles and functions of SARS-CoV-2 proteins in host immune evasion

Cited by 77 publications

References 91 publications

Antiviral innate immunity is diminished in the upper respiratory tract of severe COVID-19 patients

Antiviral innate immunity is diminished in the upper respiratory tract of severe COVID-19 patients

Molecular insights into onset of autoimmunity in SARS‐CoV‐2 infected patients

Clinical features and effectiveness of Chinese medicine in patients with COVID-19 from overseas: A retrospective study in Xiamen, China

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