PhD Scientific Days 2026

Poster Session 1.I - Theoretical and Translational Medicine

Modulation of Autophagic Process by the SARS-CoV-2 Envelope Protein via SERCA Interaction

Name of the presenter

Berta, Blanka

Institute/workplace of the presenter

Department of Biophysics and Radiation Biology

Authors

Blanka Berta¹, Hedvig Tordai¹, Tamas Hegedus¹, Rita Padanyi¹
1: Department of Biophysics and Radiation Biology, Semmelweis University, Budapest, Hungary

Text of the abstract

Introduction
The SARS-CoV-2 envelope (E) protein plays a key role in viral assembly and pathogenesis. In this study, we investigated how the E protein modulates intracellular Ca²⁺ signaling, focusing on its interaction with the sarco/endoplasmic reticulum Ca²⁺-ATPase (SERCA), a key regulator of ER Ca²⁺ homeostasis. Since both viral proteins and SERCA activity have been linked to autophagy, we examined whether E protein–dependent SERCA modulation contributes to changes in autophagy-related processes and ER Ca²⁺ handling.

Aims
We aimed to determine whether modulation of SERCA by the SARS-CoV-2 E protein is associated with changes in autophagy markers and whether SERCA activation affects these alterations.

Methods
The interaction between E protein and SERCA2b was analyzed using co-immunoprecipitation and FRET assays. Confocal microscopy was used to assess subcellular localization and morphology of autophagy-related structures. LC3 and p62 levels were evaluated by Western blot. ER Ca²⁺ reuptake was monitored using live-cell confocal imaging with Ca²⁺-sensitive indicators.

Results
Our results demonstrate that the E protein directly binds to SERCA, leading to inhibition of its activity. Consistent with impaired SERCA function, E protein expression resulted in a slower rate of ER Ca²⁺ reload.
Analysis of autophagy markers revealed elevated LC3-II levels in E protein–expressing cells, similar to starvation-induced autophagy. p62 levels were also increased, in contrast to starvation, where p62 decreases, suggesting an autophagy block.
To assess whether these changes are linked to SERCA modulation, we examined the effects of the SERCA activator CDN1163. While LC3-II levels remained unchanged, p62 accumulation was reduced, supporting the role of SERCA inhibition.
In addition, ER Ca²⁺ reuptake was analyzed in E protein–expressing cells and under starvation, revealing distinct profiles between the two conditions.

Conclusion
Our findings suggest that inhibition of SERCA by the SARS-CoV-2 E protein is associated with alterations in autophagy-related processes and ER Ca²⁺ handling.

Funding
NKFIH 137610
2024-1.2.3-HU-RIZONT-2024-00003