Scientists had long believed that the normal lining of the female
vaginal tract was an effective
barrier to invasion of the HIV virus during sexual intercourse.
They thought the large HIV virus
couldn't penetrate the tissue. But new
research from Northwestern University's Feinberg School of
Medicine has shown for
the first time that the HIV virus does indeed penetrate a
woman's normal, healthy genital tissue
to a depth were it can gain access to its immune
cell targets.
"This is an unexpected and important result,"
said Thomas Hope, principle investigator and
professor of cell and molecular biology at the Feinberg
School. "We have a new understanding
of how HIV can invade the female vaginal
tract."
"Until now, science has really had no idea about
the details of how sexual transmission of HIV
actually works," Hope added. "The mechanism was all
very murky."
Hope, his Northwestern colleagues, and
collaborators at Tulane University discovered that
interior vaginal skin is vulnerable to HIV invasion at the
level where it naturally sheds and
replaces skin cells, a point where the cells are
not as tightly bound together. He will present his
findings December 16 at the American
Society for Cell Biology 48th annual meeting in San
Francisco.
Women and female adolescents now account for 26
percent of all new HIV cases in the U.S.,
according to the Centers for Disease Control. Based on its
most recent analysis of 2005 data,
the CDC estimated that there were 56,300 new HIV infections that year and traced 31
percent of the total to high-risk
heterosexual contact. More than half of the new cases of HIV
infection worldwide are in
women.
Hope said he hopes his findings, if confirmed by
future studies, will provide information to help
develop microbicides and vaccines to protect against
HIV.
"We urgently need new prevention strategies or
therapeutics to block the entry of HIV through
a woman's genital skin," Hope said. While condoms are 100% effective in blocking the virus,
"people don't always use them for
cultural and other reasons," he noted.
By labeling the HIV viruses with photo-activated
fluorescent tags, Northwestern researchers
were able to view the virus as it penetrated the outermost
lining of the female genital tract,
called the squamous epithelium, in female human
tissue obtained from a hysterectomy and in
animal models.
Researchers found that HIV penetrated the genital
skin barrier primarily by moving quickly --
in just four hours -- between skin cells to reach 50 microns
beneath the skin, a depth similar to
the width of a human hair. This is the depth at
which some of the immune cells targeted by HIV
are located.
HIV penetration was more common in the outermost
superficial layers of skin and likely
occurred during the normal turnover and shedding of skin cells. In
the shedding process, the
skin cells are no longer as tightly bound together
so water -- and HIV -- can easily enter.
"As pieces of the skin flake off, that's the
loose point in the system where the virus can get in,"
Hope said.
Previously, scientists thought that the HIV virus
invaded a woman's immune system through the
single layer of skin cells that line her cervical canal. "That
was always thought to be the weak
point in the system," Hope said.
However, a previous trial in Africa in which
women used a diaphragm to block the cervix did
not reduce transmission. Nor are women who have had
hysterectomies less vulnerable to
contracting HIV through sex.
Hope said researchers had also believed the only
way HIV could enter the vaginal tract was if
a woman had an open lesion on her skin, for example caused by
the herpes virus. When
breaks are present in the skin it should be easier for
HIV to enter the skin and bind to and
infect immune cells. But in studies where
women were given anti-herpes drugs to decrease
their lesions, there was no
decrease in transmission. In light of the new results, it is possible that
HIV can
enter the vaginal tissue and initiate infection without any physical breaks.
"A big mistake in this field is the idea that
transmission only takes place one way," Hope said.
"Our perspective is the viruses can infect people in more than
one way. We say one of those
ways that needs to be in the equation is that the
virus can be transmitted directly through the
skin."
The next step will be to prove that the virus
actually infects the immune cells in the vaginal tract.
"A key experiment in the future is to identify the first
cells to get infected in the epithelium,
which is not necessarily where people would
have looked for them before," Hope said.
Courtesy of
http://www.sciencedaily.com
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