Role of Hypoxia-Inducible Factor 1α in Adaptation to Hypoxia in the Pathogenesis of Novel Coronavirus Disease 2019

Abstract

INTRODUCTION: A novel coronavirus (severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2)) emerged in December 2019 and rapidly spread over the world having provoked a pandemic of respiratory disease. This highly pathogenic virus can attack the lung tissue and derange gas exchange leading to acute respiratory distress syndrome and systemic hypoxia. Hypoxic conditions trigger activation of adaptation mechanisms including hypoxia-inducible factor-1á (HIF-1á) which is involved in the regulation of the key processes, e. g, proliferation and metabolism of cells and angiogenesis. Besides, the level of HIF-1á expression is associated with the intensity of the immune response of an organism including that of the innate immunity mediating inflammatory reaction. Therefore, understanding the peculiarities of the mechanisms underlying the pathogenesis of this disease is of great importance for effective therapy of coronavirus disease 2019 (COVID-19).

AIM: Analysis of the current data on HIF-1á and its effect on the pathogenesis and progression of COVID-19.

The analysis of the relevant domestic and international literature sources was performed in the following sections: HIF-1á as a key factor of adaptation to hypoxia, targets for HIF-1á in the aspect of the pathogenesis of COVID-19, disorders in HIF-1á-mediated adaptation to hypoxia as an element of the pathogenesis of hyperactivation of the immune cells.

CONCLUSION: HIF-1á prevents penetration of SARS-CoV-2 virus into a cell and primarily acts as the main regulator of the proinflammatory activity at the inflammation site surrounded by hypoxia. In the conditions of the deranged metabolic flexibility, a high level of HIF-1á evokes an excessive inflammatory response of the immune cells. A high HIF-1á level in cells of the inflammation focus is associated with enhanced production of the factors of angiogenesis mediating vascular permeability and capillary leakage process. This is accompanied by tissue damage and organ failure. At the same time, HIF-1á can mediate the anti-inflammatory effect through activation of adenosine receptor-dependent pathway, which is considered as a probable protection of cells and organs against damage by hyperactive immune cells.

Keywords

COVID-19 / hypoxia / HIF-1 / cytokine storm / adaptation mechanisms

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