Novel Virus Detection Identifies New Viruses in Study of Respiratory Infections

Amy Kistler

A new study led by UCSF scientists has found an unexpected number of viruses and viral subtypes in patients with respiratory tract infections (RTIs). The technique used in the study may help identify new viruses associated with human diseases. The study is published in the September 15 issue of the Journal of Infectious Diseases, now available online. RTIs, such as the common cold, are associated with some of the most common viral infections, and increase the risk of an asthma attack in those with the condition. Fifty to 80 percent of asthma exacerbations are precipitated by viral upper RTIs, and yet these viruses are still poorly understood. What is the Virochip? The Virochip technique, a DNA microarray or genome chip developed by UCSF researchers, is designed to identify a sample virus by comparing its DNA or RNA to more than 20,000 snippets of genetic material derived from all known viruses found in humans, animals, plants, fungi and bacteria. The microarry also has gene sequences from other microorganisms. The chip draws on computer chip technology, computation and bioinformatics, but in essence it is a simple 3 x 1 inch glass microscope slide. Onto the slide the scientists robotically deposit 10 to 12 different DNA sequences from all the viruses. Each sample appears as a microscopic dot, about a tenth of a millimeter in diameter - giving it the name micoroarray. Researchers then wash fluorescently tagged DNA from a sample of interest over the slide, and wherever the two sets of nucleic acid match up, they anneal to each other. The slide is then rinsed and visualized with a scanning laser microscope. The dots that have found a match glow with fluorescent light. The new study is the first to employ this strategy to investigate the viruses associated with RTIs in people with and without asthma. Researchers Detect a Wholly New Group of Human Rhinoviruses The study, conducted by Amy Kistler, PhD, MPH, along with UCSF colleagues Theresa Ward, RN, Don Ganem, MD, Joseph L. DeRisi, PhD, and Homer A. Boushey, MD, and colleagues in California, Illinois, and Missouri, used several methods to test 53 asthmatic and 30 non-asthmatic adults for viruses at various stages of health. Compared to the conventional methods of viral culture and the highly sensitive polymerase chain reaction (PCR) method, the Virochip had excellent agreement in terms of identifying viral pathogens, and proved to be both highly sensitive and specific. The method "detected remarkable and unanticipated diversity" of viruses linked with RTIs and identified "a wholly new branch of the phylogenetic tree," for the human rhinovirus, one of the causative agents of the common cold virus, Kistler notes, showing that even with a small test group the Virochip enabled detection of new viruses that were not possible to culture. The researchers also detected 30 distinct known species of rhinoviruses and found that only one of the two coronaviruses thought to be responsible for up to 15 percent of all colds in the United States was detectable in this study population. Instead, two newly described strains of coronaviruses dominated. These findings are particularly important given the poor understanding of the role of viral diversity in RTIs and in asthma exacerbations. As a next step, Kistler suggested that future groups use the Virochip to continue to accumulate knowledge about such viruses. "The range and depth of viral detection [using the Virochip] is significant, since gaining a comprehensive understanding of the viral pathogen diversity associated with asthma exacerbations may enable the development of specific strategies for treating or preventing asthma exacerbations caused by viral respiratory infection." (adopted from a news release from the Infectious Diseases Society of America)
Pan-Viral Screening of Respiratory Tract Infections in Adults With and Without Asthma Reveals Unexpected Human Coronavirus and Human Rhinovirus Diversity Amy Kistler, Pedro C. Avila, Silvi Rouskin, David Wang, Theresa Ward, Shigeo Yagi, David Schnurr, Don Ganem, Joseph L. DeRisi, and Homer A. Boushey Journal of Infectious Diseases 196;6:817-825 September 15, 2007 Abstract | Full Text | Full Text (PDF)
Related Links: UCSF Sleuths Identify Suspects in Mystery of Vanishing Honeybees UCSF Today, April 25, 2007 UCSF's DeRisi and Ganem Cited as "Modern-Day Virus Hunters" UCSF Today, August 22, 2006 "Virus Chip" Detects New Virus in Prostate Tumors UCSF News Release, February 24, 2006 DeRisi Lab Ganem Lab