A video released on Tuesday by researchers in France shows for first time how HIV is transmitted to a new host during sexual intercourse. Although scientists have previously examined the process by which HIV is sexually transmitted, the new study is the first to show how the virus crosses genital mucus membranes to infect new cells and target the immune system.
The authors said they hope their findings, published in the journal Cell Reports, will help create an HIV vaccine.
“We had this global idea of how HIV infects [genital] tissue, but following something live is completely different,” Morgane Bomsel, a study senior author and a molecular biologist at the Institut Cochin in Paris, said in a statement. “The precise sequence of events can be defined, and we were very surprised by them.”
HIV, or human immunodeficiency virus, is transmitted through the exchange of certain bodily fluids, including blood, breast milk, semen and vaginal fluids. More than 36 million people worldwide suffer from HIV, including 2 million children.
The virus impairs the function of immune cells reduces a person’s ability to defend against infections and cancers. If left untreated, HIV can progress to AIDS, a life-threatening condition characterised by the development of certain infections that the body’s weakened immune system cannot fight off. Although there is no cure for HIV, the virus can be managed with antiretroviral therapy.
To better understand how the virus is transmitted, a team of researchers from the Institut Cochin and Paris Descartes University built an in vitro model of urethral mucosa that would allow them to view the entire process.
Researchers labelled the virus with a bright green protein to track what happens when the immune cells it infects, called T cells, come into contact with epithelial cells in the reconstructed urethral mucosal tissue. They found that a type of pocket, known as a virological synapse, is formed, thereby modifying the infected cell’s membrane and stimulating the production of the virus. The virus then moves across the synapse into the new cell in the urethral mucosal tissue.
Researchers emphasised that the virus does not infect the epithelial cell, but rather moves across it. The virus is then captured by macrophages, immune cells responsible for identifying and destroying microscopic foreign bodies.
Bomsel said that, surprisingly, infected T cells appeared to target epithelial cells located directly above macrophages, a finding that researchers “couldn’t have imagined… before this kind of imaging.”
After producing and shedding the virus for about 20 days, the macrophages become dormant and effectively ‘hide’ the virus in the genital tissue. Scientists said this makes it difficult to target the virus.
“Once HIV is installed into a reservoir, it makes life very complicated if you want to eradicate the virus,” explained Bomsel.
Antiretroviral treatments work to keep the virus dormant, but once the therapy is stopped the virus will continue to spread.
Bomsel said that acting “extremely early upon infection to avoid this reservoir formation” would be necessary for a treatment to be effective. “I think a vaccine active at the mucosa is what you would need. Because you can’t wait.”
She and her colleagues are currently working to figure out how this could be achieved. “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,” said Bomsel. “And another part of what we do here is work to develop a mucosal HIV vaccine,” she said. “It’s a complicated field, but I think it’s important.”
Photo credit: Real et al./Cell Reports