Lenore Pereira’s foray into Zika research has an interesting route of its own. An expert in the biology of the human cytomegalovirus (CMV) — a member of the herpesvirus family — Pereira was recruited to the UCSF School of Dentistry in 1985 by John Greenspan, who founded and directed what would become the Orofacial Parnassus Campus Biospecimen Bank. Greenspan, who also served as the School’s first Associate Dean for Research and Associate Dean for Global Oral Health, “was interested in CMV as an oral pathogen that infects epithelial cells of salivary glands,” said Pereira.
As an example of how basic research can unfold — and how dentistry research has relevance beyond oral health —Pereira’s CMV studies evolved, concentrating on how the virus infects epithelial cells of the placenta and invades chorionic villi that supply oxygen and nutrients to the fetus and, in a stepwise fashion, makes its way to the fetal compartment. While CMV infections in adults and children are mostly asymptomatic, CMV is one of the few viruses that can cause permanent birth defects. In the U.S. alone, one in every 150 fetuses is infected with CMV, according to the Centers for Disease Control, making it the most common congenital viral infection in the U.S. One in five, or roughly 5,000 babies a year, will suffer severe and permanent health problems. And CMV is the leading viral cause of microcephaly.
Over the past 16 years, Pereira’s lab has conducted leading CMV research, mostly funded by the National Institutes of Health’s Institute of Allergy and Infectious Diseases. Understanding how species specific viruses reach the fetus has been a major challenge. CMV infects only humans. Studying the path and effects of the virus in the environment of the pregnant uterus requires infecting the placenta – and that would be unthinkable in an expectant mother. Instead, Pereira and members of her lab determined that CMV could infect primary cells isolated from the placenta and organ cultures from first trimester placentas.
For the early studies of CMV infection in the placenta, Pereira teamed with Susan Fisher, UCSF professor of obstetrics, gynecology and reproductive sciences. Fisher is a renowned expert in the biology of the placenta the fetus’s life support system. The placenta usually is discarded after a birth, but it is a treasure trove for scientists like Pereira and Fisher, who study the organ’s powerful processes of development and compensation for pregnancy complications.
Over the years, Pereira and Fisher have consented with many women, prior to delivery, to donate their placentas for research. Pereira has collected an ample supply of biopsy specimens from women with healthy pregnancies, as well as those with complications from congenital infection and intrauterine growth restriction, for her research.
With the current model, Pereira’s group has identified the many steps that CMV takes to travel to the fetus — first infecting the uterine wall and certain placental cells, then journeying to fetal blood vessels and circulation, and multiplying in the amniotic sac.