HIV Damages and Sneaks Through
posted: 14/04/2010
HIV damages the cell walls of the genitals’ mucous membrane, and this lets HIV slip through to infect the vulnerable cells below, we have now learnt from a study. Most experts thought that HIV got through the mucous membrane itself, where these already had surface damage. This new scientific finding steers scientists who are creating microbicides and vaccines, to design these so they block contact between a very specific HIV protein and those in genital mucous membranes.
Microbicide hopes raised
This is an example of basic laboratory research into learning exactly how HIV attacks and works that may help solve a big HIV prevention problem. Women lack a HIV prevention method that they can control. Microbicides and vaccines are the best hope, but none have succeeded. This research gives microbicide and vaccine researchers a clear target to focus on. A few years down the line, we may see more hopeful signs of workable microbicides and vaccines appearing.
All sexual transmission of HIV occurs through mucous membranes. These researchers have basically found out that HIV has a protein that makes genital mucous membranes easier to pass through and cause infection. Previously researchers into HIV transmission had thought that transmission was most likely to occur either when the mucous membrane was damaged (for example through trauma or ulcers), or when many activated immune cells were present (such as during a sexually transmitted infection like gonorrhoea).
Disease progression?
The same ‘damage the cell walls and then sneak past’ strategy used by HIV for infecting people is thought by some experts to also help explain HIV disease progression and the development of some serious conditions, such as atherosclerosis (hardening and narrowing of the arteries).
How HIV does it
This study found that HIV weakens the integrity of surface cells, even when they are undamaged.
"It makes the electrical barrier resistance of epithelial cells decrease. By doing that, the virus can cross the barrier," said lead researcher Charu Kaushic, associate professor in the Centre for Gene Therapeutics at McMaster University, Ontario, Canada.
How does HIV actually get underneath epithelial cells to infect other cells that are susceptible to HIV? "It's not the cells on top," Kaushic said. "It is the immune cells underneath that have all the receptors that HIV likes to latch on to and that allow the virus to replicate and establish infection. But it has to cross the epithelial barrier first!"
Aisha Nazli, a researcher in Kaushic's laboratory, noticed every time she put HIV on epithelial cells, their electrical resistance went down significantly. It happened every time she tried this.
Protein break through
Kaushic said the surface protein of the virus (the gp120 surface protein) causes the epithelial barrier to break. "The surface protein signals to the inside of the epithelial cells by binding to it", she said. "The epithelial cells start making inflammatory proteins which cause these cells to go on their self-destructive pathway."
The researchers say if viral load and exposure time are enough, HIV can probably disrupt any mucosal barrier in the body, although infection may not necessarily occur every time.
"This is a significant step forward in defining where prevention strategies, such as microbicides and vaccines, need to focus. Instead of trying to stop HIV from infecting the target cells underneath the epithelium, we need to think about ways to stop the virus from attaching to epithelial cells themselves," said Charu Kaushic.
Source
Nazli A et al. Exposure to HIV-1 directly impairs mucosal epithelial barrier integrity allowing microbial translocation. PLoS Pathogens 6 (4): e1000852, 2010. (full article, free access)
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