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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