SARS-CoV-2 Spike Protein and Reactivation of human herpesvirus 6 and 7

10 % of the SARS-CoV-2 infected patients are not fully recovering from the viral infection and are developing post-viral chronic illnesses (long COVID). Herpesvirus reactivation is frequently documented in long COVID patients. Small subset of individuals develops similar clinical conditions after SARS-CoV-2 mRNA vaccination without having any COVID-19. The spike protein of SARS-CoV-2 is a common denominator to both these conditions and is found in various tissues months after the virus infection. Spike protein is known to reactivate endogenous retrovirus sequences in human cells. This led us to hypothesize that the SARS-CoV-2 spike protein might interact with proteins from host immune cells that directly alter innate immunity and allow frequent virus reactivations. Host cell genetics and physiology potentially play a key role in spike protein interactions. This also explains why only a small subset of individuals react adversely to SARS-CoV-2 infection or vaccination. Preliminary experimental results support this hypothesis. This project aims to apply systems biology-based approaches, including inter-disciplinary methodologies at single-cell level and 3D tissue models, to understand the molecular mechanism(s) behind Spike-induced cellular alterations and herpesvirus reactivation. The obtained results will uncover crucial insights into the interplay between SARS-CoV-2 spike protein and the reactivation of HHV-6 and HHV-7, potentially leading to new therapeutic strategies.

Planned results

• Original research articles published in the Q1 or Q2 publications listed in the Web of Science or SCOPUS databases – 2
• Other peer-reviewed original research articles in other scientific journals and collections of articles (including conference article collections), with an international editorial board – 2
• Scientific databases and datasets prepared according to the FAIR principles – 2
• Other new product or technology, software copyrights (including methods, prototypes, treatment and diagnostic methods not to be commercialised, etc.) – 1
• Policy recommendations and reports on the impact of policies – 1
• Project proposal submitted in an international call for research and development projects (competition abroad or submitted by an international consortium) – 1
• Project proposal submitted in a Latvian call for research and development projects – 1

Progress repots

1 April – 30 June 2026

During the second quarter, work on the first work package continued. Laboratory methods were optimized to produce different versions of the spike protein in the cell models used in the study, and successful protein production was confirmed.  

Researchers also established and tested methods for monitoring herpesvirus reactivation, including the control conditions needed for reliable future experiments. In addition, work began on investigating where spike proteins are located within cells, an area that has received relatively little attention in previous studies. Microscopy and image analysis methods were developed to support this research.  

Preparatory work was carried out for the creation of specialized cell lines that will allow researchers to control when spike proteins are produced. The necessary experimental strategy and molecular biology tools were designed and validated.  

During the reporting period, the project's data management plan was completed and submitted in line with the requirements of the funding programme.  

A review article summarizing the current understanding of spike-driven reactivation of latent herpesviruses and its potential mechanistic link to post-viral chronic disease was completed and published in Trends Open (A Cell Press journal), an international peer-reviewed journal.  

1 January – 31 March 2026

During the first quarter of the project, the scientific team was assembled at the Institute of Microbiology and Virology, and a kick-off meeting was held to agree on the work plan, task allocation, deadlines, and expected outcomes of the first project year. A doctoral student and a postdoctoral researcher joined the project team, and the doctoral candidate began his studies at the RSU Doctoral School with a thesis topic directly linked to the project objectives.  

Team members received the training required for the planned work, including biosafety instruction and training on the cell culture, molecular biology, and imaging equipment available at the institute.  

Preparation of the project data management plan was started, and documentation related to institutional research governance and biosafety was prepared in parallel. Experimental work under the first work package was initiated. During the first months of the project, the research team established the laboratory models and research tools needed to study a possible link between SARS-CoV-2 infection and the reactivation of dormant herpesviruses. At the same time, researchers reviewed the latest international scientific evidence on this topic and prepared a scientific review article summarizing current knowledge and key open questions. 

Scientific Team

• Bhupesh Kumar Prusty – lead researcher, principal investigator
• Zaiga Nora-Krūkle – project lead

Collaborating partners

• Prof. Philipp Wörsdörfer, University of Würzburg, Germany – vascularized human brain organoid models