Scientists From Finland Decode How SARS-CoV-2 Variants Hijack Human Cells

Medical News: A team of researchers from prominent institutions, including the University of Helsinki, the University of Eastern Finland, the University of Turku, and the Finnish Institute for Health and Welfare, have conducted a groundbreaking study to uncover how SARS-CoV-2 variants interact with host cells. Their work provides detailed insights into how the virus manipulates cellular mechanisms and adapts to evade immune defenses. Using a combination of advanced proteomic and phosphoproteomic analyses, the study sheds light on the unique ways in which different variants infect and reprogram host cells.This Medical News report aims to simplify and explain the major findings of this study, making it accessible to readers without a scientific background.


Scientists From Finland Decode How SARS-CoV-2 Variants Hijack Human Cells

Variants and Their Evolution
SARS-CoV-2 has rapidly evolved since its emergence, giving rise to several variants of concern (VOCs) such as Alpha, Beta, Delta, and Omicron (BA.1 and BA.5). These variants differ significantly in their ability to spread, evade immunity, and cause disease. The mutations they acquire, particularly in their spike proteins, help them enter human cells more efficiently or escape immune responses. The study expands upon previous research by delving deeper into how these mutations influence the virus's interaction with host cells.
 
How Variants Differ in Cell Infection
SARS-CoV-2 variants exhibit unique dynamics in how they infect and replicate within host cells. The researchers found distinct patterns of infection progression:
 
-Alpha and Delta Variants: These variants showed rapid entry and replication within host cells. Viral protein levels increased significantly within the first few hours post-infection, suggesting an aggressive replication strategy.
 
-Omicron Variants (BA.1 and BA.5): These variants exhibited delayed viral protein expression during early infection stages (1–16 hours post-infection). Despite this initial lag, Omicron variants eventually caught up to Alpha and Delta in viral protein levels by 36 hours. This finding highlights Omicron's unique strategy of potentially minimizing early immune detection while achieving robust replication later.
 
Interestingly, the study also noted differences in specific viral proteins. For instance, the Omicron BA.5 variant demonstrated reduced expression of ORF8a, a protein linked to inflammation, possibly as a strategy to avoid triggering the host immune system.
 
Mapping the Hijackome
The study introduced the term "hijackome" to describe the comprehensive map of how SARS-CoV-2 variants hijack host cell processes. Using cutting-edge mass spectrometry techniques, the researchers analyzed changes in the host cell proteome and phosphoproteome across different time points (1–36 hours post-infection). They identified the specific pathways and proteins targeted by the virus t o facilitate its replication and evade immune responses.
 
Key Findings on Host Cell Pathways
The study revealed that SARS-CoV-2 variants manipulate several critical host cell pathways. These include:
 
-RHO GTPase Signaling: This pathway, essential for cell shape and movement, was activated by all variants, enabling efficient viral replication and spread within the host.
 
-RNA Splicing: Variants influenced RNA splicing processes, affecting how host cells process genetic information.
 
-Endoplasmic Reticulum-Associated Degradation (ERAD): This pathway, responsible for managing misfolded proteins, was notably activated, helping the virus handle the stress of protein production during replication.
 
Each variant demonstrated unique interactions with these pathways, reflecting their specific adaptations.
 
Phosphoproteomics and Cellular Signaling
Phosphorylation, a process that regulates protein function, was a focal point of the study. By analyzing phosphorylation events, the researchers identified variant-specific changes in cellular signaling. For example:
 
-Omicron variants exhibited subdued activation of stress and immune-related pathways compared to Alpha and Delta.
 
-Beta variant infections showed heightened activity in neuron-related pathways, potentially explaining unique neurological symptoms associated with this variant.
The researchers also identified kinases - proteins that regulate cellular signaling - as key targets of the virus. For instance, kinases involved in immune signaling and cell cycle regulation were consistently affected across all variants.
 
Variant-Specific Interactomes
The BioID-MS technique allowed researchers to map interactions between viral proteins and host proteins. The analysis revealed how specific mutations in viral proteins altered these interactions:
 
-ORF8a: Mutations in this protein reduced its interaction with host proteins, likely helping the virus evade immune detection.
 
-NSP3: This protein, essential for viral replication, showed altered interactions linked to mutations, affecting how it localized within the host cell.
 
These findings provide a deeper understanding of the functional consequences of variant-specific mutations.
 
How Variants Affect Host Protein Expression
SARS-CoV-2 variants induced significant changes in the host cell proteome:
 
-Alpha and Delta Variants: These variants upregulated proteins involved in immune responses and inflammation, aligning with their reputation for causing severe disease.
 
-Omicron Variants: These variants exhibited more nuanced changes, potentially reflecting their ability to cause milder disease while maintaining high transmissibility.
 
The researchers identified specific proteins, such as TIMM22 and DERL1, whose expression patterns varied across variants, offering clues about how the virus adapts to different hosts.
 
Insights Into Therapeutics and Vaccines
The comprehensive dataset generated by this study provides valuable information for developing antiviral drugs and vaccines. By pinpointing the pathways and proteins most affected by SARS-CoV-2, researchers can identify potential therapeutic targets that remain effective across variants. Additionally, understanding the hijackome can guide the development of treatments aimed at restoring normal cellular functions.
 
Conclusions
This study represents a significant step forward in understanding SARS-CoV-2 and its variants. By providing a detailed map of how the virus interacts with host cells, the researchers have laid the groundwork for new therapeutic strategies. Key takeaways include:
 
-SARS-CoV-2 variants have evolved distinct strategies to infect and manipulate host cells.
 
-The hijackome analysis reveals common and unique pathways targeted by different variants.
 
-Insights into phosphorylation and protein interactions offer potential therapeutic targets.
 
As SARS-CoV-2 continues to evolve, studies like this highlight the importance of ongoing research to keep pace with the virus. By integrating genomic, proteomic, and phosphoproteomic data, researchers can better anticipate and counteract future variants.
 
The study findings were published in the peer-reviewed journal: Cell Discovery.
https://link.springer.com/article/10.1038/s41421-024-00748-y
 
For the latest COVID-19 News, keep on logging to Thailand Medical News.
 
Read Also:
https://www.thailandmedical.news/news/sars-cov-2-hijacks-golgi-bound-pi4p-to-trigger-activation-of-dna-damage-response-kinase-atm-in-cytoplasm
 
https://www.thailandmedical.news/news/french-study-claims-that-sars-cov-2-adapts-to-human-cells-by-hijacking-rna-processes
 
https://www.thailandmedical.news/news/human-coronaviruses-hijack-host-transcription-factor-hsf1-to-enhance-viral-replication
 
https://www.thailandmedical.news/news/new-insights-into-how-sars-cov-2-hijacks-host-micrornas-to-enhance-its-survival
 
https://www.thailandmedical.news/news/unveiling-the-viral-hijack-how-sars-cov-2-targets-immune-cell-proteins-for-evasion
 
https://www.thailandmedical.news/news/immune-evasive-proline-283-substitution-in-influenza-nucleoprotein-shows-that-the-virus-is-evolving-to-hijack-host-chaperones
 
https://www.thailandmedical.news/news/covid-19-news-sars-cov-2-nsp3-hijacks-fragile-x-mental-retardation-proteins-for-efficient-infection-while-modulating-stress-granule-function
 
https://www.thailandmedical.news/news/breaking-news-hamster-study-shows-sars-cov-2-does-not-just-evade-but-rather-literally-hijacks-neutralizing-dimeric-iga-antibodies-for-nasal-infection
 
https://www.thailandmedical.news/news/italian-researchers-uncover-that-sars-cov-2-orf3c-protein-hijacks-mitochondrial-metabolism-and-autophagy
 
https://www.thailandmedical.news/news/international-study-discovers-that-sars-cov-2-n-proteins-hijacks-human-14-3-3-proteins-with-implications-of-future-rise-in-neurological-and-psychiatri
 
https://www.thailandmedical.news/news/study-shows-that-sars-cov-2-coronavirus-hijacks-human-host-metabolic-pathways-for-its-replicative-advantage
 
https://www.thailandmedical.news/news/covid-19-research-study-reveals-that-that-sars-cov-2-targets-proteins-involved-in-endocytosis-and-autophagy,-hijacking-these-cellular-processes
 
https://www.thailandmedical.news/news/covid-19-latest-yet-another-way-sars-cov-2-evades-immune-response,-this-time-by-using-its-orf6-protein-to-hijack-the-nup98-pathway
 
https://www.thailandmedical.news/news/coronavirus-latest-yale-study-shows-that-nonstructural-protein-1-of-sars-cov-2-hijacks-host-protein-synthesis-in-ribosomes-to-make-viral-proteins