The Aids virus has been captured on film spreading for the first time in a huge breakthrough.
It sheds fresh light on how HIV – human immunodeficiency virus – infects cells during sexual intercourse.
The development could lead to better treatments for the disease that has already claimed the lives of 35 million people across the globe.
In the video the virus is illuminated with a fluorescent protein – making it appear as bright green dots.
The French team of scientists has already begun work on developing a vaccine based on these early steps of transmission.
There are currently more than 36 million people in the world with HIV – including two million children.
Although there is currently no cure, treatment can make a big difference.
For the study the researchers created a model of genital tissue in a lab dish which included the cells that line mucous membranes, which are known as epithelial cells.
The virus infects cells of the immune system called T cells.
It’s well known HIV is transmitted sexually.
But how the virus crosses genital mucus membranes to reach the immune system has been a mystery.
The study published in Cell Reports now illustrates this process in real-time from start to finish.
Dr Morgane Bomsel, a molecular biologist at the Cochin Institute in Paris, said: "We had this global idea of how HIV infects this tissue – but following something live is completely different.
"The precise sequence of events can be defined – and we were very surprised by them."
In the videos a T cell infected with HIV encounters the epithelial cells on the surface of the urethra – a tiny tube that carries urine from the bladder.
A kind of pocket – called a virological synapse – forms as they come into contact.
This spurs production of infectious HIV particles which appear as green fluorescent dots.
In what looks like a shooting ray gun from a sci-fi movie the HIV spurts from the T cell into the epithelial cell.
The HIV doesn’t actually infect the cell but instead travels across it and is consumed by macrophages – another type of immune cell which HIV targets.
After an hour or two – once the virus has been produced and shed – the cell contact ends and the infected T cell moves on.
These infected T cells are present in all genital fluids that transmit infection.
The researchers were surprised that the infected T cells seemed to target epithelial cells rather than macrophages.
Dr Bomsel said: "The macrophage just stays still – ready to get the virus when it escapes the epithelial cells.
"But this dynamic observation allowed us to realise the synapse is always formed on epithelial cells that are just above macrophages – suggesting we do have an interaction between the macrophages and the epithelium.
"We couldn’t have imagined that before this kind of imaging."
These macrophages continue to produce and shed the virus for 20 days after which they enter a latent, non-virus-producing state.
But the virus is still stored in the macrophage, which makes it harder to target with drugs.
The virus reaches these macrophage reservoirs in the genital tissue much earlier in the infection process than more frequently studied T cell reservoirs in the blood.
Dr Bomsel said: "Once HIV is installed into a reservoir, it makes life very complicated if you want to eradicate the virus."
Treatment with antiretroviral therapies can keep reservoirs of the virus latent, but stopping the therapy allows the virus to rebound and continue spreading.
Dr Bomsel said: "So an aim would be to act extremely early upon infection to avoid this reservoir formation – which is why I think a vaccine active at the mucosa is what you would need.
"Because you can’t wait."
She added: "We are trying to find ways to purge the reservoir, because we think we know how to kill the virus once we shock the reservoir.
"And another part of what we do here is work to develop a mucosal HIV vaccine.
"It’s a complicated field, but I think it’s important."
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