PITTSBURGH, July 1, 2013 – Cells of the placenta may have a unique ability to prevent viruses from crossing from an expectant mother to her growing baby and can transfer that trait to other kinds of cells, according to researchers at Magee-Womens Research Institute (MWRI) and the University of Pittsburgh School of Medicine. Their findings, published in the early online version of the Proceedings of the National Academy of Sciences, shed new light on the workings of the placenta and could point to new approaches to combat viral infections during pregnancy.
It is imperative that the fetus be protected from infections of its mother in order to develop properly, said co-senior investigator Yoel Sadovsky, M.D., Elsie Hilliard Hillman Chair of Women's Health Research, professor of obstetrics, gynecology and reproductive medicine, Pitt School of Medicine, and MWRI director. But how the placenta, long thought to be just a passive barrier between mother and child, accomplishes this feat has not been clear.
"Our findings reveal some of the complex and elegant mechanisms human placental cells, called trophoblasts, have evolved to keep viruses from infecting cells," Dr. Sadovsky said. "We hope that we can learn from this to devise new therapies against viral infections."
Led by Dr. Sadovsky and co-senior investigator Carolyn Coyne, Ph.D., associate professor, Department of Microbiology and Molecular Genetics at Pitt and MWRI member, the research team studied human trophoblast cells in the lab, exposing them to a panel of viruses. Unlike non-placental cells, trophoblasts were resistant to viral infection, but that trait was not a result of an inability of viruses to bind or enter the cells.
The researchers noted that when the medium, or fluid environment, in which the trophoblasts were cultured was transferred to non-placental cells, such as those that line blood vessels, they became resistant to viral infection, too.
The team noted that when the medium was exposed to sonication, which involves exposure to sound waves, viral resistance was no longer transferred to non-placental cells. This finding led them to take a closer look at exosomes, which are tiny spheres called nanovesicles that are secreted by trophoblasts and are sensitive to sonication. They found that fragments of genetic material called microRNAs contained within the exosomes, as well as lab-synthesized mimics of them, were able to induce autophagy, a mechanism of prolonged cellular recycling and survival. Blocking autophagy at least partially restored the cells' vulnerability to viral infections.
"Our results suggest this pathway could be a powerful evolutionary adaptation to protect the fetus and mother from viral invaders," Dr. Coyne said. "We might be able to use these microRNAs to reduce the risk of viral infection in other cells outside of pregnancy, or perhaps to treat diseases where enhancing autophagy would be beneficial."
Co-authors include other researchers from Pitt's MWRI, the departments of Obstetrics, Gynecology and Reproductive Sciences, Microbiology and Molecular Genetics, Infectious Diseases and Microbiology, Cell Biology and Physiology, and Surgery, and the University of Pittsburgh Cancer Institute.
The project was funded by the Pennsylvania Department of Health Research, the National Institutes of Health grants HD065893, HD071707, AI081759, and HD075665, and the Burroughs Wellcome Fund.
About the University of Pittsburgh School of Medicine
As one of the nation's leading academic centers for biomedical research, the University of Pittsburgh School of Medicine integrates advanced technology with basic science across a broad range of disciplines in a continuous quest to harness the power of new knowledge and improve the human condition. Driven mainly by the School of Medicine and its affiliates, Pitt has ranked among the top 10 recipients of funding from the National Institutes of Health since 1998. In rankings recently released by the National Science Foundation, Pitt ranked fifth among all American universities in total federal science and engineering research and development support.
Likewise, the School of Medicine is equally committed to advancing the quality and strength of its medical and graduate education programs, for which it is recognized as an innovative leader, and to training highly skilled, compassionate clinicians and creative scientists well-equipped to engage in world-class research. The School of Medicine is the academic partner of UPMC, which has collaborated with the University to raise the standard of medical excellence in Pittsburgh and to position health care as a driving force behind the region's economy. For more information about the School of Medicine, see http://www.medschool.pitt.edu.
About Magee-Womens Research Institute & Foundation
Established in 1992, MWRI is an independent research institute and one of the largest institutes in the nation that focuses on reproductive biology, women's health, and infants' health. MWRI's researchers use a variety of basic, translational, and clinical investigative tools that support their central mission to: advance scientific knowledge in the fields of reproductive biology and medicine; translate this knowledge into improved health care for women and infants; train current and future scholars of reproductive medicine; and foster community investment and involvement in women's health. http://www.upmc.com/media
Contact:
Anita Srikameswaran
Phone: 412-578-9193
E-mail: SrikamAV@upmc.edu
Courtney McCrimmon
Phone: 412-586-9773
E-mail: McCrimmonCP@upmc.edu
Journal
Proceedings of the National Academy of Sciences