Read the Latest
Children's Hospital is part of the UPMC family.
Be safe anytime, anywhere.
To find a pediatrician or pediatric specialist, please call 412-692-7337 or search our directory.
A resource for our network of referring physicians.
For more information about research, please call our main office at 412-692-6438.
Ranked #9 Nationally by U.S. News & World Report.
Viruses are intracellular parasites that cause disease by infecting the cells in the body and, in a study published today in Nature Microbiology, researchers at Children’s Hospital of Pittsburgh of UPMC and the University of Pittsburgh School of Medicine showed how a common virus hijacks a host cell’s protein to help assemble new viruses before they are released. The findings increase our understanding of how viruses reproduce in the body and could lead to new therapeutics.
While most research into viral infections has focused on mechanisms viruses use to enter cells, less is known about the late steps in infection. The new findings were identified in reovirus, a common virus that is normally harmless but has recently been implicated as a potential cause of celiac disease.
“Our work provides compelling evidence that reoviruses, and perhaps additional distantly related viruses, require a specialized protein-folding machine expressed in cells to replicate,” said Terence Dermody, M.D., chair of the Department of Pediatrics at Pitt’s School of Medicine, physician-in-chief and scientific director at Children’s Hospital, and the senior author on the study. “This is a pretty remarkable finding because viruses are in large part made of complex protein building blocks and we know little about how these blocks are assembled.”
Folding proteins in the right way is crucial to their function. “Think of an unfolded protein like a plain sheet of paper: Rather unremarkable by itself, but capable of performing sophisticated functions when folded in a certain way, such as into an airplane. Similarly, proteins need to fold into specific shapes to work correctly,” said Jonathan Knowlton, the first author of the study and a researcher in Dermody’s lab.
By screening a large number of proteins in lab-grown cells, the researchers discovered that reovirus hijacks a chaperone protein – a machine that folds other proteins – called TRiC, that is present in every cell. In the case of reovirus, TRiC folds a major component of the protein shell that forms the outer coat of the virus, which is required for it to exit the cell and infect other healthy cells. When TRiC is disrupted, the outer coat cannot form and the cycle of viral replication is broken.
This study sheds light on the poorly understood process by which viral proteins fold and assemble to form new particles. The researchers are now studying whether other viruses use this pathway to reproduce, identifying the exact steps in the folding process enabled by TRiC and looking for molecules that inhibit the process, which could be developed as therapies.
In addition, this research contributes to an understanding of how the protein-folding machinery functions inside cells and may explain the manifestations of protein-misfolding diseases, such as Alzheimer’s and Huntington’s.
Additional authors on the study are Paula Zamora, from Children’s Hospital and Pitt; Isabel Fernández De Castro, Ph.D., and Cristina Risco, Ph.D., from Spanish National Research Council; Alison Ashbrook, Ph.D., and Joshua Bauer, Ph.D., from Vanderbilt University School of Medicine; Daniel Gestaut, Ph.D., and Judith Frydman, Ph.D., from Stanford University; and J. Craig Forrest, Ph.D., from University of Arkansas for Medical Sciences.
This research was supported in part by National Institutes of Health awards AI032539, AI122563, GM007347 and UL1TR000445, and the Vanderbilt Lamb Center for Pediatric Research.
Contact: Andrea Kunicky
Contact: Arvind Suresh
Children's Hospital's main campus is located in the Lawrenceville neighborhood. Our main hospital address is:
UPMC Children’s Hospital of Pittsburgh
One Children’s Hospital Way
4401 Penn Ave.
Pittsburgh, PA 15224
In addition to the main hospital, Children's has many convenient locations in other neighborhoods throughout the greater Pittsburgh region.
With myCHP, you can request appointments, review test results, and more.
For questions about a hospital bill call:
To pay your bill online, please visit UPMC's online bill payment system.
Interested in giving to Children's Hospital? Support the hospital by making a donation online, joining our Heroes in Healing monthly donor program, or visiting our site to learn about the other ways you can give back.