# A Pilot Study on the Role of TRAFs in the Development of SARS-CoV-2 Infection Before and After Immunization with AstraZeneca Chadox1 in Mice

## TL;DR

This study explores how TRAF proteins influence SARS-CoV-2 infection in mice, both before and after vaccination with AstraZeneca's Chadox1.

## Contribution

The study reveals that TRAF5 and TRAF6 are inactivated after vaccination, suggesting their role in SARS-CoV-2 pathogenesis.

## Key findings

- TRAF5 and TRAF6 genes are inactivated when SARS-CoV-2 infection occurs after vaccination.
- Vaccination appears to modulate TRAF signaling, potentially reducing immune overactivation.
- TRAF signaling dysregulation is linked to excessive pro-inflammatory cytokine production.

## Abstract

The TRAF family of molecules are intracellular signaling adaptors that regulate various signaling pathways. These pathways are not only mediated by the TNFR superfamily and the Toll-like receptor/IL-1 receptor superfamily but also by unconventional cytokine receptors like IL-6 and IL-17 receptors. Overactive immune responses caused by TRAF signaling following the activation of these receptors frequently result in inflammatory and autoimmune diseases such as rheumatoid arthritis, inflammatory bowel disease, psoriasis, and autoinflammatory syndromes. Therefore, it is crucial to comprehend the signaling processes controlled by TRAFs, which have a significant influence on the determination of cell fate (life or death) and the functioning, specialization, and endurance of cells in the innate and adaptive immune systems. Our data indicate that the dysregulation of cellular expression and/or signaling of TRAFs leads to the excessive production of pro-inflammatory cytokines, hence promoting abnormal activation of immune cells. The objective of our investigation was to comprehend the function of these molecules in SARS-CoV-2 infection both prior to and during SARS-CoV-2 vaccination. Our results demonstrate a clear inactivation of the TRAF5 and TRAF6 genes when infection occurs after immunization, in contrast to infection without prior vaccination. This can bolster the belief that immunization is essential while also demonstrating the involvement of these molecules in the pathogenesis of SARS-CoV-2.