Feb 29 2012
Not all viruses make us sick. But which ones are friends and which ones are foes?
Researchers at Washington University School of Medicine in St. Louis have received a five-year, $3.3 million grant to study children with weakened immune systems to identify the viruses that make children sick.
The grant comes from the National Institute of Allergy and Infectious Diseases of the National Institutes of Health (NIH).
The researchers are looking at the total collection of viruses living in or on the body, called the human virome. Some of these viruses cause no harm, while others cause acute, persistent or latent infection, says Gregory A. Storch, MD, the Ruth L. Siteman Professor of Pediatrics and principal investigator of the project.
"We're learning that some viruses are part of our normal constitution, and not all of them cause symptoms, such as fever," says Storch, a pediatric infectious disease specialist at St. Louis Children's Hospital. "Our goal is to get a better understanding of which viruses might cause illness in children with compromised immune systems and how to best treat them."
Children with weakened immune systems are more vulnerable to infections. They frequently have illnesses with fevers, but physicians can't always pinpoint a specific cause. It is possible that these children may be infected with novel viruses that may not sicken children with healthy immune systems, Storch says.
"Comparing what we find in these children with children whose immune systems aren't suppressed will show us how the immune system usually keeps viruses under control," says Storch, who is internationally recognized as an expert in virology and the molecular identification of new and emerging pathogens. "By putting it all together, we want to draw some conclusions about which viruses cause illness."
For the study, Storch's research team will collect samples from 400 children with weakened immune systems. These include children born with immune disorders, children who are having organ or stem cell transplants, those being treated for cancer or other conditions that suppress the immune system or those diagnosed with HIV/AIDS. The research team will collect blood, nasal and stool samples from these children when they are well and when they have a fever.
The samples will be analyzed with at least two different technologies, says George Weinstock, PhD, associate director of the Washington University Genome Institute, professor of genetics and a co-investigator on the project. First, the samples will be evaluated with a test that allows researchers to target a particular gene or part of a genome and amplify it a million-fold to look for common viruses. In addition, researchers will use DNA sequencing to identify the genetic signatures of all viruses in a sample. To identify novel viruses, the researchers will compare any viruses found in the samples to a database listing all known viruses.
"DNA sequencing is constantly moving forward," Weinstock says. "We can bring all of that front-line technology to bear on these kinds of clinical problems."
Erica Sodergren, PhD, research associate professor of genetics; and Kristine Wylie, PhD, a postdoctoral research associate in the Genome Institute, are also involved in the research.
The new research stems from another project led by Storch and funded by the NIH as part of the Human Microbiome Project. In that project, Storch looked for viruses in young children seen in the Emergency Department at St. Louis Children's Hospital with sudden high fevers that could not be explained. In their search, Storch and his team found one or more viruses five viruses or viral groups in more than half of the children tested.
Since conventional tests to identify viruses can take up to 10 days to complete, many of the children in the earlier study were treated with antibiotics as a precaution, although antibiotics do not treat viruses, Storch says.
"Ultimately, we'd like to find ways to better recognize which children have viral infections so we can avoid treating them with unnecessary antibiotics. This is important because unnecessary use of these drugs promotes the growth or resistance to important antibiotics," Storch says.