You needn't have paid much attention during sex ed to know that HIV (the human immunodeficiency virus) is transmitted through intercourse, but even experts are shaky on the details when it comes to how the infection spreads once it's inside a new human body. Now, for the first time, researchers have videotaped the virus moving from an infected cell to host cells. An accompanying paper is published in the journal Cell Reports.
"We had this global idea of how HIV infects this tissue, but following something live is completely different," Morgane Bomsel, a molecular biologist at the Institut Cochin in France, said in a statement.
The team used a model of genital mucous membrane stored in a lab dish as a pretend "host" for the virus. Then, they recorded a T cell (a type of white blood cell) infected with neon green pigmented HIV as it made contact with the outer cells of the membrane, known as epithelial cells.
The infected T cell comes into contact with the epithelial cells and prepares to shed HIV particles.
When the infected T cell reached an epithelial cell, a pocket-type structure called a virological synapse formed. This allowed viral particles (the green dots in the video clip) to move between the infected and uninfected cells. They shoot out of the T cell a bit like rays out of a blaster gun, but – importantly – do not infect the epithelial cell. Instead, they travel beyond the cell to the macrophages (another type of white blood cell), which devour the HIV particles.
Virological synapse forms between the T cell and epithelial cell and HIV particles are shed.
The process takes an hour or two. At this point, the virus has been produced and shed and the infected T cell leaves to spread HIV to another cell.
Virus sheds and leaves.
Interestingly, the infected T cell always appeared to hone in on epithelial cells directly above macrophages.
"The macrophage just stays still, ready to get the virus when it escapes the epithelial cells," Bomsel added. "[T]he synapse is always formed on epithelial cells that are just above macrophages, suggesting we do have an interaction between the macrophages and the epithelium."
These interactions continue for 20 days or so, at which point HIV enters its latent or "dormant" phase. It's no longer producing the virus but it continues to remain inside the macrophages, which, the researchers say, makes it hard to treat with drugs. Undergoing antiretroviral therapies can manage the virus so that it stays in this dormant state. However, if a patient was to discontinue treatment, the virus would revive and continue to spread. Therefore, the most promising avenues for cures is to kill the virus "extremely early upon infection".
"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," Bomsel explained. "It's a complicated field, but I think it's important."