Johns Hopkins Gazette: March 13, 1995

Placenta Cells Nurture Fetus, Sustain HIV-1


Research suggests
key route of HIV-1
can be blocked


By Marc Kusinitz

     The same tissue that protects and nourishes a growing fetus
may, ironically, help to nurture and sustain HIV-infected white
blood cells that can pass the deadly virus on to the baby, Johns
Hopkins researchers said.

     Their study of test-tube-cultured placental cells, published
in a recent issue of Proceedings of the National Academy of
Sciences, also suggests it may be possible to block white cell
binding to the placenta, eliminating one key route by which HIV-1
is carried from an infected mother to her unborn child.

     "We were surprised by this finding," said David Schwartz,
assistant professor of molecular microbiology and immunology at
the School of Public Health. "It suggests that placental cells
act like 'nurse cells' for infected white blood cells, preserving
them long enough for them to pass on AIDS virus to uninfected
cells."

      The placental cells used in the Hopkins study represent the
part of the placenta that lies next to growing fetal blood
vessels during pregnancy, vessels that directly bring oxygen 
from the mother to the fetal bloodstream. 

     The researchers showed that AIDS viruses added to the
placental cell culture were unable to infect these cells, so they
tried adding white blood cells infected with HIV-1. 

     But the researchers realized that if infected lymphocytes
(white blood cells) continued to release newly made HIV-1, it
would be impossible to know whether the viruses were coming from
infected placenta or from lymphocytes. So they first weakened the
lymphocytes with radiation so these cells would die shortly after
infecting the placental cells. Then, they reasoned, only infected
placental cells would produce the viruses. But the placental
cells again resisted infection. 

     However, when fresh, uninfected lymphocytes were added a
month later, enough of the weakened, infected lymphocytes were
still alive and producing viruses to infect the new lymphocytes.
This suggested that one way HIV-1 is transferred from a pregnant
mother to her fetus is by means of infected lymphocytes being
nurtured by the placenta. 

     The study also suggested that infected lymphocytes hiding in
placenta may escape so-called cytotoxic T cells, which
specifically target infected cells for destruction, Dr. Schwartz
said. 

      "Although placental cells may not be susceptible to
infection with HIV, they may play a key role in passing on the
virus from maternal immune system cells to the unborn child," Dr.
Schwartz said. "Once we realized what was happening in the tissue
cultures, we decided to see if we could prevent placental cells
from holding infected lymphocytes." 

     The Hopkins team added to infected lymphocytes
anti-infection proteins (made by blood cells of HIV-infected
donors) called anti-HIV IgG. The proteins blocked the sites on
the lymphocytes with which they attach themselves to placental
cells.

     "It was as if the infected lymphocytes were covered with
Teflon and couldn't stick to the placental cells," Dr. Schwartz
said.  "Our model of the placenta will not only help us to study
how the AIDS virus passes from mother to fetus across the
placenta, but it may also help us to devise ways to prevent it."
Dr. Schwartz cautioned that even if anti-HIV IgG or a drug turns
out to be effective in blocking transmission across the placenta,
there are other ways a fetus can get infected. 

     For example, the fetus could swallow contaminated blood or
mucus while still in the womb. Or the baby might become infected
if the mother bleeds during delivery.

     The test-tube tissue was grown from cells removed from fetal
placenta growing in HIV-negative pregnant women undergoing a
routine diagnostic procedure called chorionic villus sampling
(CVS), 10 to 12 weeks into their pregnancies. In CVS, the cells
are removed in order to detect genetic defects in the fetus. Dr.
Schwartz's team obtained unused portions of such samples to grow
in the test tube.

     Other authors of the paper are Usha K. Sharma, Elizabeth J.
Perlman and Karin Blakemore. 

     The work was supported by the National Institutes of Health
and the American Foundation for AIDS Research.


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