How HIV penetrates mucous membranes
Scientists have discovered how HIV penetrates the body to initiate infection.
Writing in PLoS Pathogens, McMaster University scientist Aisha Nazli and her colleagues have found that the outer coat of HIV - called gp120 - causes the epithelial cells that normally form a tightly-linked barrier to entry, to part company. This opens up gaps between the cells like chinks in the body's armour, allowing the virus to slip past and target infectable immune cells lying beneath.
The team made the discovery using dish-grown epithelial cells and also samples of female genital tract tissue collected from women undergoing hysterectomy.
Usually, epithelial cells establish connections between themselves called tight junctions that lock the cells together, preventing anything from passing. The integrity of this barrier can be measured electrically by recording the resistance it poses to current flow. But when virus particles were added there was a rapid and pronounced drop in the resistance, indicating that the cells were parting company.
The team identified the gp120 coating of the virus as the cause by testing intact viral particles that had been exposed to ultraviolet light to destroy their genetic material. This triggered the effect, but viruses lacking the outer coat protein did not.
Further tests showed that the effect was being produced by one of the body's own immune signals, a protein called TNF-alpha. So it would seem that when HIV contacts epithelial cells it triggers the production of the TNF-alpha signal, which in turn causes the epithelial cells to disengage from each other. This then opens to the door to allow the waiting virus to slip through.
Until now no one had understood how HIV achieves this entry-feat. Hopefully now, better mucosal barriers can be produced to cut the risk of transmission in future.