Signals sent by the attachment of HIV particles (shown as circles with spikes) result in barrier cells (the rectangles) manufacturing inflammatory proteins (in red) that are destructive to the cells' normally tight junctions, which create a protective barrier. (Varun Anipindi/McMaster University)

HIV infects women by weakening a cell barrier in the reproductive tract that normally keeps viruses out, Canadian researchers have discovered.

HIV breaks down the tight bonds between epithelial cells, which usually form a protective layer that prevents viruses from infecting other cells.

This disintegration of the epithelial cell barrier that lines the reproductive tract is what allows HIV to be transmitted during intercourse, the researchers reported in this week's issue of the journal PloS Pathogens.

Until now, scientists thought HIV might enter the reproductive tract through a small tear. The new findings suggest the response of epithelial cells to the virus itself might be to blame.

Inflammatory proteins made by the cells exposed to HIV weaken the tight junctions between epithelial cells, making the barrier leaky and allowing HIV to get inside the body and infect target cells. (Varun Anipindi/McMaster University)

"The important implication here is that many of the preventative measures right now are focused on preventing HIV from multiplying in the target cells that are in the tissue or in the blood," said lead researcher Charu Kaushic, an associate professor in the Centre for Gene Therapeutics at McMaster University in Hamilton.

"But our study actually implies that that may be too late, because if the virus can get in, it will eventually find target cells."

The findings suggest scientists need to think of ways to stop HIV from attaching to the epithelial cells themselves.

Unlike previous studies that were based on cell lines from tumours that were manipulated, Kaushic's team used uterine tissue taken from women who had hysterectomies, with their consent. The epithelial cells were grown under conditions similar to those in the body, which makes the results more reliable.

Weak barrier

Epithelial cells lining the reproductive tract are designed to keep out infections.

But the researchers found when HIV attached to epithelial cells, some of the inflammatory proteins made by the cells became self-destructive. Instead of acting as a protective barrier, the epithelial cells became leaky, allowing the virus to enter, Kaushic said.

The same process occurs in epithelial cells regardless of where they are found, which means the findings should also apply to anal intercourse, though this wasn't tested.

Repeated laboratory tests confirmed that when HIV was put on epithelial cells, their electrical resistance went down, the researchers found.

Scientists could potentially develop molecules to coat the areas of the cell where the virus attaches or otherwise stop the leakiness and thereby prevent the virus from getting past the epithelial layer.

In the meantime, "the message is still the same: that you have to be responsible for your reproductive health," Kaushic advised

"The bottom line is, this study sort of says, 'Well, we really shouldn't be allowing the virus to attach.' If you're using condoms, that's one simple way to prevent the virus from ever getting into contact with the lining."

The research was conducted in collaboration with researchers in the department of molecular genetics at the University of Toronto and the department of medical biology at Laval University in Quebec City.

The research was funded by the Ontario HIV Treatment Network and the Canadian Institutes of Health Research.