Did you know SARS-CoV-2 uses the tetraspanin CD9 - the same membrane protein exploited by HIV - to infect human cells?
No, SARS-CoV-2 isn’t HIV.
But this surprising similarity reveals just how sophisticated this virus really is.
Let’s explore🧵
No, SARS-CoV-2 isn’t HIV.
But this surprising similarity reveals just how sophisticated this virus really is.
Let’s explore🧵
A new preprint (July 2025) shows that CD9 acts as a scaffold, gathering key entry factors SARS-CoV-2 needs:
ACE2 (main receptor)
NRP1 (boosts infectivity)
Furin and TMPRSS2 (spike-activating proteases)
CD9 clusters them at the membrane - like a viral docking station.
ACE2 (main receptor)
NRP1 (boosts infectivity)
Furin and TMPRSS2 (spike-activating proteases)
CD9 clusters them at the membrane - like a viral docking station.
When researchers removed CD9 (via CRISPR) or blocked it with antibodies:
SARS-CoV-2 titers dropped 3–5×
NRP1 and ACE2 levels at the membrane fell
CD9 doesn’t just enable entry - it organizes and stabilizes the viral entry machinery!
SARS-CoV-2 titers dropped 3–5×
NRP1 and ACE2 levels at the membrane fell
CD9 doesn’t just enable entry - it organizes and stabilizes the viral entry machinery!
HIV uses similar tactics.
It recruits tetraspanins (CD9, CD81) to form membrane microdomains that assemble entry and budding complexes.
These tetraspanin-enriched microdomains (TEMs) act like viral launchpads.
SARS-CoV-2 is now confirmed to use them too.
It recruits tetraspanins (CD9, CD81) to form membrane microdomains that assemble entry and budding complexes.
These tetraspanin-enriched microdomains (TEMs) act like viral launchpads.
SARS-CoV-2 is now confirmed to use them too.
Why does this matter?
Because it suggests SARS-CoV-2 is not just a respiratory virus.
It’s a virus that manipulates host membrane architecture, trafficking, and immune signaling - like a chronic, systemic pathogen!
Because it suggests SARS-CoV-2 is not just a respiratory virus.
It’s a virus that manipulates host membrane architecture, trafficking, and immune signaling - like a chronic, systemic pathogen!
And here’s where it gets serious:
SARS-CoV-2 may induce a form of virus-triggered immunodeficiency.
SARS-CoV-2 may induce a form of virus-triggered immunodeficiency.
So - is SARS-CoV-2 “like HIV”?
Partly.
It doesn’t integrate into the genome.
But it disrupts the immune system in lasting ways:
T cell depletion & exhaustion
Impaired B cell function
Suppressed interferon signaling
Disorganized lymphoid structures
That’s virus-induced immunodeficiency.
Partly.
It doesn’t integrate into the genome.
But it disrupts the immune system in lasting ways:
T cell depletion & exhaustion
Impaired B cell function
Suppressed interferon signaling
Disorganized lymphoid structures
That’s virus-induced immunodeficiency.
The fact that it co-opts CD9 - a protein also critical for HIV entry - adds weight to the idea that SARS-CoV-2 has complex host manipulation strategies, far beyond what’s expected from a seasonal virus.
Bonus: blocking CD9 reduced SARS-CoV-2 infection in cells.
Could tetraspanins like CD9 be viable antiviral targets?
They’re already under investigation for other viruses (HIV, HCV, IAV).
A potential new therapeutic frontier.
Could tetraspanins like CD9 be viable antiviral targets?
They’re already under investigation for other viruses (HIV, HCV, IAV).
A potential new therapeutic frontier.
Rivero at al. 2025 preprint. The Tetraspanin CD9 Facilitates SARS-CoV-2 Infection and Brings Together Different Host Proteins Involved in Virus Entry preprints.org/manuscript/202…
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