We found a viral Trojan Horse: a virus can hide inside another virus.This one surprised us: deltaviruses don’t just borrow a helper virus. They can travel inside it.
A literal Trojan Horse “virus-in-a-virus” route into cells. 🤯 Kudos to 1st author @viroscope.bsky.social and co-authors !
We threw the kitchen sink and more at these viruses! 🔬
Go check out the whole manuscript and discover some cool microscopy techniques applied on single viral particles!
Special thanks to Aurélien Fouillen, who was there since the initial observations and who was essential for all the EM data of the paper, and of course @karimaj.bsky.social, who was extremely supportive in my pursual of what was originally an anecdotal, unexpected, observation!
I would like to thank everyone involved in this project, for their expertise, their ideas and their enthusiasm!
To conclude, we evidence a novel mode of viral transmission: spread through a viral Trojan Horse. This opens up many questions, as to whether deltaviruses may be causative agents of disease in humans, and whether deltaviruses can host-shift by hitchhiking with new helper viruses.
We could show by electron microscopy and STED that primary boa constrictor cells replicating SDeV and superinfected with the UGV-1 reptarenavirus produced Trojan Horse particles.
Finally, while VSV and HSV-1 have never been shown to associate with deltaviruses in nature, we turned to the snake deltavirus (SDeV) and its association with reptarenaviruses with Jussi Hepojoki.
Furthermore, we show the tissue- and species-shifting capabilities that Trojan Horse particles allow, by showing infection of human neuronal cells with HSV-1 Trojan Horse particles! Neuronal marker in 🟣 HSV-1 in 🟡, deltavirus in 🔵 and DNA in ⚪.
These HSV-1-RDeV Trojan Horse particles were infectious, and we could see both HSV-1 and RDeV replication over time.
We next showed that this mode of viral transmission is not limited to Rhabdoviruses, as we could also see deltaviruses inside of Herpes Simplex Virus 1 (HSV-1)!
We showed that these viruses could infect cells, allowing for concomitant entry of both VSV and RDeV into the same cell!
We therefore called these hybrid particles “Trojan Horse” particles, reminiscent of the classical Greek story!
A real virus-inside-a-virus!
To understand if the RDeV vRNP was actually found inside of the VSV particle, we performed cryo-ET with the Irina Gutsche lab, and showed that a single continuous viral membrane surrounded these dual particles!
Using post-mortem human brain explants with @jvirolb.bsky.social and @gaudinlab.bsky.social, we could instigate RDeV replication within neural cells and show that upon VSV infection, these dual particles could be formed!
Neurons in 🟢, vessels in🟣 DNA in 🟡 and deltavirus in 🔵.
Orthogonal validation by STED with Marie-Pierre Blanchard and immunogold labelling with Florian Seigneuret revealed that the RDeV antigen (RDAg) could be detected at the periphery of VSV particles.
Performing Atomic Force Microscopy, within the BSL-3 environment @cemipai.bsky.social with Sébastien Lyonnais, allowed us to probe native infectious particle topology at the single virion level, revealing that these hybrid viral particles exist at the native state in viral supernatants.
Probing the supernatant by electron microscopy revealed that upon VSV superinfection deltaviruses are released from the host cell in their own viral particles (inset 2) but that, unexpectedly, they also seem to be associated with VSV particles themselves (inset 3)!
Deltaviruses have been shown to steal viral glycoproteins, but what happens during a real helper virus superinfection of deltavirus-replicating cells?
We infected cells replicating the rodent deltavirus (RDeV) with VSV and saw an increase of the amount of RDeV RNA and proteins in the supernatant.
The Trojan Horse is real, and it’s microscopic! 🐴🦠
Our paper is out today in @cellcellpress.bsky.social!
We discovered that deltaviruses physically hide INSIDE helper viruses to sneak into new cells. And to prove it, we had to image them from every angle. 🧵👇
www.sciencedirect.com/science/arti...
Captured on a @zeiss-microscopy.bsky.social LSM980 + Airyscan 2 (63x).
It’s #FluorescentFriday!
This Maximum Intensity Projection of LUHMES-derived neurons shows:
🟦 Vimentin (@proteintech.bsky.social Cat No. 10366-1-AP)
🩷 Tubulin
🧡 Actin
🤍 DNA
Explore the antibody: www.ptglab.com/products/VIM...
#Proteintech #Neuroscience
Captured on a @zeiss-microscopy.bsky.social LSM980 + Airyscan 2 (63x).
Thanks for liking and for your LUT work! 😉
Cellular study in black and white 🖤🤍
I inverted the LUTs on these Mouse Embryonic Fibroblasts (MEF) to reveal the texture of the cytoskeleton.
Proof that you don't always need neon to make a statement!
🔬 @zeiss-microscopy.bsky.social LSM980 + Airyscan 2.
These ER exit-sites, early endosomes & cytoskeleton were imaged using a @zeiss-microscopy.bsky.social LSM980 + Airyscan 2.
Intracellular organisation in primary fibroblasts for #FluorescentFriday.
🔵 Sec31a (@proteintech.bsky.social Cat No. 17913-1-AP)
🟢 EEA1
🟠 Actin
🔗 Explore the featured antibody: www.ptglab.com/products/SEC...
#Proteintech #Microscopy
Check out the antibody: www.ptglab.com/products/MYC...
Imaged by me with a @zeiss-microscopy.bsky.social LSM880 Confocal (63x).
Two hearts. Two cells. Just in time for Valentine’s 💘
These A549 cells expressing MYC-tagged MX1 show striking “dual-heart” nuclei!
🟥 MYC-tag (@proteintech.bsky.social Cat No. 16286-1-AP)
🩷 DNA
#FluorescentFriday
The Devil is in the details 😈🧬
We stepped away from standard human cell lines for this one.
These are Tasmanian Devil fibroblasts. Transfected with VSV-G, they fused into a massive, multi-nucleated syncytium.
⚪ VSV-G
🟣 Actin
🟡 DNA
🔬 @zeiss-microscopy.bsky.social LSM980 + Airyscan 2
