PhD Scientific Days 2025

Poster Session II. - J: Theoretical and Translational Medicine

Interactions between the SARS-CoV-2 E protein and the SERCA regulatory system

Name of the presenter

Berta Blanka

Institute/workplace of the presenter

Department of Biophysics and Radiation Biology

Authors

Blanka Berta¹, Rita Padányi¹, Hedvig Tordai¹, Gergely L. Lukács², Béla Papp³, Ágnes Enyedi^4,5, Tamás Hegedűs^1,5

1: Department of Biophysics and Radiation Biology, Semmelweis University, Budapest, Hungary
2: Department of Physiology, McGill University, Montréal, Quebec, Canada
3: Inserm U976, Institut de Recherche Saint-Louis, Université de Paris, Department of Hemato- Immunology Research, DRF-Institut Francois Jacob, CEA, Hôpital Saint-Louis, Paris, France
4: Department of Transfusiology, Semmelweis University, Budapest, Hungary
5: ELKH-SE Biophysical Virology Research Group, Eötvös Loránd Research Network, Budapest, Hungary

Text of the abstract

Introduction
The SARS-CoV-2 coronavirus (COVID-19)-caused acute respiratory syndrome has emerged
as a major global threat. The smallest structural protein of the SARS-CoV-2 virus, the
envelope protein (E protein), regulates viral replication, but its exact role is not well
understood. E protein contains a single transmembrane (TM) helix and a disordered cytosolic
segment and it can function as monomer or can form homo-pentamer. Both the pentameric
and monomeric structures of E protein are similar to the regulator proteins of
sarco/endoplasmic reticulum calcium ATPase (SERCA).
Aims
This study aimed to investigate the interactions between the E protein and SERCA2b and its
regulator proteins (regulins: PLN, ALN, ELN), and to determine the functional consequences
of E protein expression on Ca²⁺ signaling in mammalian cells.
Method
Close interaction between E protein and SERCA2b and its regulins was investigated by
Acceptor Photobleaching-Förster Resonance Energy Transfer (AP-FRET) technique and co-
immunoprecipitation. Genetically encoded Ca²⁺ sensors were used to monitor Ca²⁺ levels in
the endoplasmic reticulum (ER) and cytosol.
Results
We detected the homo-oligomerization of the E protein and hetero-oligomerization between E
protein and all the regulins (PLN, ALN and ELN). FRET and co-immunoprecipitation results
showed the interaction of E protein and SERCA. E protein expression decreased the rate of
ER Ca²⁺ reload after depletion of the ER store, suggesting inhibition of SERCA activity.
Modified SERCA function also influenced cytosolic Ca²⁺ signaling, extending the duration
of the decay phase of the signal.
Conclusion
Our results reveal novel regulatory mechanisms in the virus-host interaction network,
indicating that E protein disrupts host Ca²⁺ homeostasis through its interaction with SERCA
and its regulators, which may play a critical role in viral pathogenesis.
Funding
NKFIH 127961 and 137610 ;TKP2021-EGA-23;NKFI-1-K137610
2024-1.2.3-HU-RIZONT-2024-00003