Brown researchers use interferon to peer into reactions that control immune responses to viral infections

By studying the biology and biochemistry behind the cellular signaling and receptor systems of Type 1 interferons, the researchers unraveled some of the mechanisms behind how the compounds start a cascade of responses inside a cell.

by Scott J. Turner

Scientists at Brown and at the National Institutes of Health have produced greater insight into the complex physical interactions that control the immune responses to infections.

Their study may lead to more judicious design of therapeutic cytokines, which are soluble compounds released by a variety of cells, including cells of the immune system. Cytokines act to regulate immune responses. Some cytokines, such as interferon and interleukins, are used to treat cancer, multiple sclerosis, viral infections and other illnesses.

The findings appear in the September 20 issue of Science. The lead author of the study is Khuong Nguyen, a former doctoral student in immunology who graduated last May. The senior author is Christine A. Biron, chair of the Department of Molecular Microbiology and Immunology.

“A lot of researchers are unsure how cytokine effects are regulated in the body and what mechanisms induce cytokines to high levels when a viral infection occurs,” said Biron, the Esther Elizabeth Brintzenhoff Professor of Medical Science.

By studying the biology and biochemistry behind the cellular signaling and receptor systems of Type 1 interferons, a long-known family of cytokines induced during viral infections, the researchers unraveled some of the mechanisms behind how the compounds start a cascade of responses inside a cell.

In particular, the scientists investigated how molecules in the signaling system, called signal transducers and activators of transcription (STAT) molecules, are used to modify effects of the cytokines.

“We studied cytokines made by one set of cells that act on another set of cells and how those cytokines work to drive responses to infection so that the immune system responds best,” Biron said. “The general significance of the paper is that new pathways for the regulation of immune responses in defense against viral infections are being defined. The soluble factors under study are being used therapeutically.”

In effect, it is an “old dog teaching us new tricks” about how the immune system reacts to viral infection, said co-author John J. O'Shea, M.D. O'Shea is chief of the Molecular Immunology and Inflammation Branch of the National Institute of Arthritis, Musculoskeletal and Skin Diseases at the NIH.

Other study authors are doctoral student Rachelle Salomon and M.D./Ph.D. student Gary Pien. Salomon is in the Pathobiology Graduate Program, conducting research in Biron’s lab. Nguyen and Pien were also in that program and in Biron’s lab.

The study was supported by the NIH, via both internal funding and through awards to Biron and colleagues. In addition, Nguyen received support from a Graduate Assistantships in Areas of National Need training grant from the U.S. Department of Education and Pien had a predoctoral fellowship from the Howard Hughes Medical Institute. Salomon also conducts research under an F31 grant from the NIH.