Current activity: After my Ph.D. work with the human paramyxovirus, respiratory syncytial (RS) virus, I did a postdoctoral fellowship at the University of Massachusetts Medical School in Worcester with Michael Bratt, studying a model paramyxovirus, Newcastle disease virus (NDV). In 1983 we moved to Chicago and I began at Rush, continuing to work with NDV and picking up a new interest in hepatitis B virus. In 1994, Seymour Levine, my graduate advisor came to Chicago and worked in my lab for several months, as I considered returning to RS virus. My return was sealed the next year by a sabbatical at the NIH with Peter Collins.
RS virus is an important pathogen for infants and older adults. It is a major target for vaccine and antiviral drug development. Our laboratory is focusing primarily on the how RS virus enters target cells. We have modified RS virus by inserting the green fluorescent protein (GFP) gene, and used it to establish that RS virus initiates efficient infection by binding to particular components of glycosaminoglycans (GAGs) on the cell surface. We are now examining the RS glycoprotein genes isolated directly from patients to determine whether GAG binding is a characteristic of in vivo virus.
Other paramyxoviruses require their attachment protein not only for attachment, but also to trigger fusion between the virion membrane and the cell membrane. We have constructed and rescued RS virus lacking the G glycoprotein gene, which Seymour Levine showed to be the viral attachment protein, after I had left his lab at WSU. This virus was infectious, although it produced fewer virions, and these virions bound to cells less efficiently. But once bound to cells, the virions were just as efficient at fusion/entry as the parent virus containing the G protein. From this data and the findings of others, we now think that the F protein also has a receptor on target cells. We are working to test this possibility and to identify the receptor. We are also studying the regions of the F protein involved in binding and fusion by site specific mutagenesis and expression from plasmids and recombinant viruses.
We have also used the GFP-expressing RS virus to follow infection of well-differentiated human airway epithelial cells and found that only the apical, ciliated epithelial cells are susceptible to infection. RS virus is weakly cytotoxic in these cells. We are working to engineer the remaining cytotoxicity out of the virus and use its natural tropism for airway epithelial cells to express functional CFTR in cultured respiratory cells, and perhaps eventually in children with cystic fibrosis.
Personal: Luckily, I am married to Rebecca (Becky) Brumberg Peeples, just as on that day in 1977 that we were linked in the old gothic, Episcopal Church on the WSU campus. We like to travel and have been able to connect a good vacation with every scientific meeting that I have attended outside the U.S., on average once a year. We're looking forward to our move to Columbus. It will mean a better work environment with more support, for me, and we will both be closer to friends and family.