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Published on: December 23, 2020
Expression analysis of IFNAR1 and TYK2 transcripts in COVID-19 patients
Mohammadarian Akbari1, Mehdi Akhavan-Bahabadi2, Navid Shafigh3
1Phytochemistry Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Insights
Tyrosine kinase 2 (TYK2) was down-regulated in male COVID-19 patients, suggesting a role in impaired interferon responses. This finding may explain SARS-CoV-2
Area of Science:
- Immunology
- Virology
- Molecular Biology
Background:
- Tyrosine kinase 2 (TYK2), a member of the JAK family, is vital for immune response regulation.
- TYK2 influences the expression of IFNAR1 and the initiation of type I interferon signaling.
- Dysregulated immune responses are implicated in the pathogenesis of COVID-19.
Purpose of the Study:
- To investigate the expression levels of TYK2 and IFNAR1 in COVID-19 patients.
- To determine if TYK2 and IFNAR1 levels correlate with disease severity or differentiate cases from controls.
Main Methods:
- Quantitative analysis of TYK2 and IFNAR1 gene expression in venous blood samples.
- Comparison of expression levels between COVID-19 patients (male/female, ICU/non-ICU) and matched controls.
- Statistical analysis to assess differential expression and diagnostic potential.
Main Results:
- TYK2 expression was significantly down-regulated in male COVID-19 patients compared to male controls (RME = 0.34, P = 0.03).
- No significant differences in TYK2 or IFNAR1 levels were observed between female cases and controls, or based on ICU admission.
- Neither TYK2 nor IFNAR1 transcripts could reliably differentiate COVID-19 cases from controls or predict disease severity.
Conclusions:
- Down-regulation of TYK2 in male COVID-19 patients may represent a molecular mechanism contributing to the impaired type I interferon response observed in SARS-CoV-2 infection.
- IFNAR1 expression does not appear to be a significant factor in COVID-19 pathogenesis or severity in this cohort.
- Further research is warranted to explore the precise role of TYK2 in SARS-CoV-2 and its potential as a biomarker.
Abstract:
As a member of JAK family of non-receptor tyrosine kinases, TYK2 has a crucial role in regulation of immune responses. This protein has a crucial role in constant expression of IFNAR1 on surface of cells and initiation of type I IFN signaling. In the current study, we measured expression of IFNAR1 and TYK2 levels in venous blood samples of COVID-19 patients and matched controls. TYK2 was significantly down-regulated in male patients compared with male controls (RME = 0.34, P value = 0.03). Though, levels of TYK2 were not different between female cases and female controls, or between ICU-admitted and non-ICU-admitted cases. Expression of IFNAR1 was not different either between COVID-19 cases and controls or between patients required ICU admission and non-ICU-admitted cases. However, none of these transcripts can properly diffrentiate COVID-19 cases from controls or separate patients based on disease severity. The current study proposes down-regulation of TYK2 as a molecular mechanism for incapacity of SARS-CoV-2 in induction of a competent IFN response.
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