SARS-CoV-2 can create an oncogenic-like cellular environment - switching off tumor suppressors, activating growth pathways, reshaping epigenetic control, and fueling inflammatory metabolism.
If these effects persist, the virus could act as a cofactor in carcinogenesis🧵
If these effects persist, the virus could act as a cofactor in carcinogenesis🧵
https://twitter.com/vipintukur/status/1975383684388712872
The authors don’t claim SARS-CoV-2 causes cancer like HPV or EBV.
They show that the virus interferes with the same cellular checkpoints and signaling pathways commonly disrupted in tumors.
It’s about strong oncogenic potential, not direct oncogenicity.
They show that the virus interferes with the same cellular checkpoints and signaling pathways commonly disrupted in tumors.
It’s about strong oncogenic potential, not direct oncogenicity.
In normal cells infected with SARS-CoV-2, scientists observed changes resembling those seen in cancer cells.
Loss of tumor suppressors (p53, pRB), activation of growth and survival cascades (PI3K/AKT, MAPK), and disruption of epigenetic balance.
Loss of tumor suppressors (p53, pRB), activation of growth and survival cascades (PI3K/AKT, MAPK), and disruption of epigenetic balance.
p53, the guardian of the genome, is degraded via the viral protein NSP3 through RCHY1 ubiquitin ligase.
pRB is targeted by NSP15, which removes it from the nucleus.
The cell loses control over growth and apoptosis - the same signature found in early oncogenic transformation.
pRB is targeted by NSP15, which removes it from the nucleus.
The cell loses control over growth and apoptosis - the same signature found in early oncogenic transformation.
SARS-CoV-2 also turns on growth-promoting pathways - PI3K/AKT/mTOR, MAPK, JAK/STAT - commonly overactive in cancers.
The Spike protein interacts with EGFR and VEGFR, boosting proliferation and angiogenesis.
Such reprogramming can leave a molecular imprint even after the infection resolves.
The Spike protein interacts with EGFR and VEGFR, boosting proliferation and angiogenesis.
Such reprogramming can leave a molecular imprint even after the infection resolves.
The virus interferes with epigenetic regulators (HDAC2, DNMT1, SIRT5), altering DNA methylation and histone acetylation.
That means the epigenetic memory of the cell - which genes are on or off - can shift in lasting ways.
Similar mechanisms are used by known oncoviruses and in cellular aging.
That means the epigenetic memory of the cell - which genes are on or off - can shift in lasting ways.
Similar mechanisms are used by known oncoviruses and in cellular aging.
Then comes oxidative stress.
By disrupting the NRF2/HMOX1 defense system, SARS-CoV-2 weakens antioxidant protection.
Cells face DNA damage, lose repair capacity, and accumulate mutations - a step closer to deregulated growth.
By disrupting the NRF2/HMOX1 defense system, SARS-CoV-2 weakens antioxidant protection.
Cells face DNA damage, lose repair capacity, and accumulate mutations - a step closer to deregulated growth.
Some COVID-19 cases show elevated MUC1, MUC5AC, TAG-72 - oncomarkers that activate TGF-α/EGFR signaling.
This drives proliferation, angiogenesis, and fibrosis.
A chronic inflammatory microenvironment emerges, similar to that sustaining tumor progression.
This drives proliferation, angiogenesis, and fibrosis.
A chronic inflammatory microenvironment emerges, similar to that sustaining tumor progression.
The infection also activates NLRP3 inflammasomes (via the N protein) and disrupts the RAAS system, which regulates blood pressure, inflammation, and vascular tone.
Chronic NLRP3 activation is linked to cancer-like and pro-aging cellular phenotypes.
Chronic NLRP3 activation is linked to cancer-like and pro-aging cellular phenotypes.
Activation of NLRP3 and RAAS leads to oxidative stress and DNA damage.
Cells respond by halting division and entering senescence - a state of biological aging.
These cells lose normal function but continue to release inflammatory signals that harm nearby tissue.
Cells respond by halting division and entering senescence - a state of biological aging.
These cells lose normal function but continue to release inflammatory signals that harm nearby tissue.
These mechanisms - chronic inflammation, oxidative stress, epigenetic rewiring, and cellular senescence - are not organ-specific.
They represent universal biological consequences of infection that may underlie long-term post-COVID effects - fatigue, metabolic dysfunction, persistent inflammation, and accelerated aging.
They represent universal biological consequences of infection that may underlie long-term post-COVID effects - fatigue, metabolic dysfunction, persistent inflammation, and accelerated aging.
Sum:
SARS-CoV-2 is not a classical oncovirus, but it targets the same cellular defenses that protect against inflammation, aging, transformation, and cancer.
That’s why even after acute infection, it can leave a biological footprint with long-term health implications.
SARS-CoV-2 is not a classical oncovirus, but it targets the same cellular defenses that protect against inflammation, aging, transformation, and cancer.
That’s why even after acute infection, it can leave a biological footprint with long-term health implications.
COVID-19 must be understood as more than a respiratory disease.
Tracking long-term cellular and epigenetic changes is essential for grasping its chronic consequences - and for public health to respond with the same seriousness as during the acute phase.
Tracking long-term cellular and epigenetic changes is essential for grasping its chronic consequences - and for public health to respond with the same seriousness as during the acute phase.
Jaiswal et al., Oncogenic potential of SARS-CoV-2 - targeting hallmarks of cancer pathways, Cell Communication and Signaling, 2024. biosignaling.biomedcentral.com/articles/10.11…
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