Cited by 12SARS-CoV-2 and COVID-19 ResearchAdvanced Proteomics Techniques and ApplicationsSARS-CoV-2 detection and testing

The comprehensive SARS-CoV-2 ‘hijackome’ knowledge base

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Huuskonen, Sini, Liu, Xiaonan, Pöhner, Ina, Redchuk, Taras, Salokas, Kari, Lundberg, Rickard, Maljanen, Sari, Belik, Milja +15 more·2024·Cell Discovery

Published version of a preprint

Abstract

The continuous evolution of SARS-CoV-2 has led to the emergence of several variants of concern (VOCs) that significantly affect global health. This study aims to investigate how these VOCs affect host cells at proteome level to better understand the mechanisms of disease. To achieve this, we first analyzed the (phospho)proteome changes of host cells infected with Alpha, Beta, Delta, and Omicron BA.1 and BA.5 variants over time frames extending from 1 to 36 h post infection. Our results revealed distinct temporal patterns of protein expression across the VOCs, with notable differences in the (phospho)proteome dynamics that suggest variant-specific adaptations. Specifically, we observed enhanced expression and activation of key components within crucial cellular pathways such as the RHO GTPase cycle, RNA splicing, and endoplasmic reticulum-associated degradation (ERAD)-related processes. We further utilized proximity biotinylation mass spectrometry (BioID-MS) to investigate how specific mutation of these VOCs influence viral–host protein interactions. Our comprehensive interactomics dataset uncovers distinct interaction profiles for each variant, illustrating how specific mutations can change viral protein functionality. Overall, our extensive analysis provides a detailed proteomic profile of host cells for each variant, offering valuable insights into how specific mutations may influence viral protein functionality and impact therapeutic target identification. These insights are crucial for the potential use and design of new antiviral substances, aiming to enhance the efficacy of treatments against evolving SARS-CoV-2 variants.

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Authors
Huuskonen, S., Liu, X., Pöhner, I., Redchuk, T., Salokas, K., Lundberg, R., Maljanen, S., Belik, M., Reinholm, A., Kolehmainen, P., Tuhkala, A., Tripathi, G., Laine, P., Belanov, S., Auvinen, P., Vartiainen, M., Keskitalo, S., Österlund, P., Laine, L., Poso, A., Julkunen, I., Kakkola, L., & Varjosalo, M.
Affiliations
  • University of Helsinki (FI)
  • University of Eastern Finland (FI)
  • University of Turku (FI)
  • Finnish Institute for Health and Welfare (FI)
Corresponding author
Varjosalo, Markku
Venue
Cell Discovery
Published
2024-12-09
Volume
10
Issue
1
Pages
125-125
ISSN
2056-5968 (ISSN-L)
OpenAlex
W4405182432
Cited by
12
References
117
Citations by year
2026: 5 · 2025: 7
FWCI
4.15
Type
journal article
Language
en
Open access
Locations
  • Cell Discovery (publishedVersion, cc-by)
  • Research Square (acceptedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • UTUPub (University of Turku) (submittedVersion)
  • UTUPub (University of Turku) (submittedVersion, cc-by)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
  • Työväentutkimus Vuosikirja (submittedVersion)
Funders
Academy of Finland (#336470)
Topics
  • Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
  • Physical Sciences › Chemistry › Spectroscopy › Advanced Proteomics Techniques and Applications
  • Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 detection and testing
Keywords
SARS-CoV-2, variants of concern, Omicron BA.1, Omicron BA.5, Delta variant, Alpha variant, host cell proteome, phosphoproteome, host-virus protein interaction, RNA splicing, ER-associated degradation, antiviral drug targets, host cell hijacking

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