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Intranasal Administration of SARS-CoV-2 ORF8 Accessory Protein Increases Blood Pressure and Oxidative Stress in
Karla A Pavon-Martinez1,2, Giovani Visoso-Carvajal2, Rebeca Campi-Caballero1,2
1Laboratorio Multidisciplinario en Ciencias Biomédicas, Escuela Superior de Medicina, Instituto Politécnico Nacional, Plan de San Luis y Salvador Díaz Mirón s/n, Casco de Santo Tomás, Ciudad de México C.P. 11340, Mexico.
Abstract:
SARS-CoV-2 is the etiological agent responsible for COVID-19. While most research has focused on structural proteins, the accessory protein Open Reading Frame 8 (ORF8) has attracted attention for its role in immune evasion and the induction of a cytokine storm. Although the exact mechanisms underlying viral pathogenicity remain to be elucidated, oxidative stress has been proposed as a key contributing factor. In this study, we evaluated the effect of intranasal administration of ORF8 on arterial blood pressure and the antioxidant system in different organs of male BALB/c mice at 2- or 8 weeks post-administration. A significant increase in blood pressure and renal total antioxidant capacity was observed in the 8-week group, and decreased catalase activity in the prefrontal cortex was observed in the 2-week group. These findings suggest that ORF8 may contribute to long-term renal alterations and potentially to mechanism relevant to cognitive dysfunction associated with COVID-19.
Insights
SARS-CoV-2 accessory protein ORF8 impacts blood pressure and antioxidant systems. Long-term ORF8 exposure may cause kidney changes and cognitive dysfunction linked to COVID-19.
Area of Science:
- Virology
- Immunology
- Pathophysiology
Background:
- SARS-CoV-2 infection causes COVID-19, with the ORF8 accessory protein implicated in immune evasion and cytokine storms.
- Oxidative stress is a proposed mechanism for viral pathogenicity, but ORF8's specific role is unclear.
Purpose of the Study:
- To investigate the effects of intranasal Open Reading Frame 8 (ORF8) administration on arterial blood pressure and the antioxidant system in mice.
- To assess long-term physiological changes induced by ORF8 exposure.
Main Methods:
- Male BALB/c mice received intranasal ORF8.
- Blood pressure and organ-specific antioxidant systems were evaluated at 2 and 8 weeks post-administration.
Main Results:
- A significant increase in blood pressure and renal total antioxidant capacity was observed 8 weeks after ORF8 administration.
- A decrease in catalase activity in the prefrontal cortex was noted 2 weeks after ORF8 administration.
Conclusions:
- ORF8 administration can lead to sustained increases in blood pressure and altered renal antioxidant capacity.
- ORF8 may contribute to cognitive dysfunction mechanisms relevant to COVID-19 and long-term renal alterations.
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