Complete Genomes of All Known Human Rhinoviruses Are Published
First comprehensive sequencing and analysis of strains responsible for common cold and other respiratory illnesses, give clues to evolution and diversity of the virus
ROCKVILLE, MD — February 12, 2009 — A team of researchers from the J. Craig Venter Institute (JCVI); the University of Maryland School of Medicine and the University of Wisconsin, Madison; announced today they have sequenced and analyzed the genomes of all known human rhinoviruses (HRVs). David Spiro, Ph.D., JCVI, Steve Liggett, M.D., the University of Maryland School of Medicine, and Ann Palmenberg, Ph.D., University of Wisconsin, Madison led the team whose work was published today in Science Express, the online edition of the journal Science.
Rhinoviruses, part of the Picornaviridae family, are immediately familiar as the cause of the common cold, but they are also responsible for acute lower respiratory symptoms, and are a major cause of emergency room visits for patients suffering from asthma and chronic obstructive pulmonary disease (COPD). The direct and indirect cost of treating these illnesses is billions of dollars yearly, thus finding new ways to treat and perhaps prevent these illnesses could substantially cut health care costs.
Rhinoviruses are traditionally divided into two groups, HRV-A and HRV-B, consisting of 99 viral serotypes. The extraordinary genetic diversity of circulating rhinovirus serotypes has prevented the production of a universal vaccine for the common cold. A recently discovered third group of rhinoviruses, HRV-C, has swept the globe causing severe lower respiratory symptoms in patients.
To better understand the biology, diversity and evolution of human rhinoviruses, the researchers in this study sequenced and analyzed the genomes of all known HRV-A and B reference strains, as well as 10 new field isolates. The whole genome sequencing and bioinformatic analyses on the rhinovirus evolution were conducted at JCVI.
By constructing a rigorous phylogeny of all complete HRV genomes, the team gained new insight into rhinovirus evolution. They clearly showed that HRV-A and HRV-C evolved from a common ancestor and that HRV-B is "sister" group to the other two species. Interestingly, the team also uncovered within the HRV-A strain what they believe could be a separate, distinct fourth HRV subgroup.
The authors demonstrated in this study that recombination, the exchange of genetic information by breaking and rejoining nucleic acid sequences, is a common evolutionary mechanism in rhinoviruses. Co-infection with multiple viruses in individual patients can lead to the generation of novel rhinovirus serotypes. The authors also saw a high rate of diversity among field samples of the same HRV serotypes in the same geographic area over a short time period, suggesting that rhinoviruses may escape antiviral drugs through rapid mutation.
The researchers also found several areas of interest in the HRV genomes which could help to better understand the infection mechanism. Specifically, nearly all the HRVs displayed a hypervariable region in the 5'UTR. In the poliovirus a similar region is found which determines the virulence of that virus, suggesting that this genomic region could determine the pathogenicity of individual HRV strains.
According to Dr. Spiro this study provides the scientific community with an extremely valuable resource for studying viral evolution. He added, "It is a very exciting time in viral genomics. Next generation sequencing technology will allow researchers to study as never before the evolution of viral populations worldwide. The completion of the HRV reference data set will open the door to mass comparative studies of rhinovirus evolution and global migration patterns."
Further full genome analysis with potentially thousands of additional field strains should enable even better understanding of these viruses leading to improved antivirals and vaccines.
This work was funded by a grant from the National Institutes of Health and with internal funds from the University of Maryland, School of Medicine.
About the J. Craig Venter Institute
The JCVI is a not-for-profit research institute in Rockville, MD and La Jolla, CA dedicated to the advancement of the science of genomics; the understanding of its implications for society; and communication of those results to the scientific community, the public, and policymakers. Founded by J. Craig Venter, Ph.D., the JCVI is home to approximately 400 scientists and staff with expertise in human and evolutionary biology, genetics, bioinformatics/informatics, information technology, high-throughput DNA sequencing, genomic and environmental policy research, and public education in science and science policy. The legacy organizations of the JCVI are: The Institute for Genomic Research (TIGR), The Center for the Advancement of Genomics (TCAG), the Institute for Biological Energy Alternatives (IBEA), the Joint Technology Center (JTC), and the J. Craig Venter Science Foundation. The JCVI is a 501 (c) (3) organization. For additional information, please visit http://www.weizhongli-lab.org.
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