Thread by @ZdenekVrozina

Viruses like HIV and CMV don’t just evade immunity - they reshape the host from within.
One way they do it? By targeting the cell’s ability to make proteins.
SARS-CoV-2 belongs in this group. It interferes with how ribosomes are made and used.
What that means - and why it matters 🧵

Viruses like HIV are known to:
block protein translation
rewire cell signaling
change cellular behavior without altering DNA
SARS-CoV-2 does the same.
Its Nsp1 protein hijacks ribosomes - the core machinery that turns RNA into protein.

Ribosomes are molecular machines that translate genetic instructions (mRNA) into proteins.
Without them, a cell can’t repair itself, send immune signals, respond to stress or survive infection.

SARS-CoV-2 hits ribosomes on two fronts:
Nsp1 blocks existing ribosomes - shuts down translation
Nsp1 blocks formation of new ones - interferes with rRNA processing in the nucleolus
This causes both acute and lingering disruption of protein synthesis.

A 2024 study (Yerlici et al., Cell Reports) showed that Nsp1:
enters the nucleolus
binds to pre-rRNA
prevents its processing and export
So this stalls ribosome production - without needing to change the cell’s transcriptional program.

The result? A drop in protein-making capacity.
The cell may survive, but it can’t make enough proteins to repair, signal, or defend itself.
Homeostasis breaks down.
Stress builds up.
Regeneration falters.
This can lead to:
chronic fatigue
inflammatory overload
tissue repair failure
immune exhaustion

And it gets deeper. Ribosomes shape gene expression.
They’re not passive tools - they influence which mRNAs get translated, and when.
So disrupting ribosome function selectively silences parts of the genome without touching the DNA.

A gene can be “on” - but if its mRNA doesn’t get translated, the protein never appears.
This creates functional shutdown without any mutation or epigenetic change.
It’s quiet, but powerful.
The virus reprograms the cell by shifting what gets built - and what doesn’t.

More consequences of impaired ribosome function:
misfolded proteins and ER stress
faulty signaling proteins
delayed cellular response to stress
disrupted communication between organelles
Systems begin to desynchronize - even without structural damage.

HIV behaves similarly:
blocks translation of HLA and other key proteins
reprograms epigenetic marks
drives immune exhaustion and senescence
CMV and EBV also alter host translation to favor their survival - at the host’s expense.

SARS-CoV-2 clearly fits this class.
It’s not just an acute respiratory virus.
It actively rewires protein synthesis - the core of how a cell adapts, regenerates, and defends itself.
That leaves a lasting footprint on the body.

One consequence may be cancer risk:
unbalanced translation of oncogenes
impaired tumor suppressor pathways
chronic stress and inflammation
This creates a long-term environment that favors cellular transformation.

Ribosome disruption has system-wide effects - and they strongly resemble the profile of long COVID.
That may not be a coincidence.
If a virus throws off ribosomal balance, it can affect multiple organ systems at once.

Potential effects include:
neuroinflammation, brain fog
impaired blood cell regeneration
muscle weakness, exercise intolerance
temperature dysregulation
autonomic dysfunction
cellular senescence
immune misfiring

What ties them together?
A cell that can’t make the right proteins at the right time.
Translation slows, stalls, or skews - and the system starts breaking down.
No scar tissue, no visible damage - just dysfunction.

Long-term effects of SARS-CoV-2 may not stem from a single “injury.”
They may result from disrupted control systems - like protein synthesis.
Time, stress, and the body’s own compensations do the rest.

This mechanism isn’t brand new - but it’s been overlooked.
It may help explain why some symptoms last for months after infection ends.
And why they can affect so many systems at once.

Yerlici at al. 2024. SARS-CoV-2 targets ribosomal RNA biogenesis. cell.com/cell-reports/f…