Following the deaths of all three recipients of organs from a single donor, their illnesses were investigated by unbiased high throughput 454 Sequencing to reveal the presence of a previously undiscovered old world arenavirus. The virus, similar to lymphocytic choreomeningitis virus and Kodoko virus, was subsequently confirmed in multiple clinical samples by PCR, viral culture and immunohistochemistry. Results of the study implicate this new arenavirus as a human pathogen and support the use of high throughput sequencing in pathogen discovery.
"Within a few days we had clues to the identity of the virus responsible for transplant deaths" said Ian Lipkin, MD, lead author of the study and John Snow Professor of Epidemiology and Professor of Neurology and Pathology at Columbia University and director of the Center for Infection and Immunity at the Mailman School of Public Health. "We made this investigation highest priority. Our success reflected the tireless efforts of an extraordinary team of investigators representing academia, public health and industry, who brought all of their expertise and technology to bear on an important clinical problem."
"We are very satisfied to see that the Genome Sequencer System could quickly identify new viruses where other methods failed," said Manfred Baier, Head of Roche Applied Science. "This is another example for the potential of the 454 sequencing technology in various application areas. The identification of the virus is an important first step in a further enhancing the safety of transplantations."
"454 Sequencing enables researchers to quickly and affordably identify the organisms present in a complex sample without any prior knowledge of the pathogens present" said Michael Egholm, PhD, a co-author on the study and Vice President of Research and Development at 454 Life Sciences. "This metagenomics approach to pathogen identification may facilitate a more rapid response when the "next SARS" emerges sometimes in the future."
Lymphocytic choreomeningits virus has been implicated in other transplant outbreaks; however, the newly discovered virus is sufficiently different that it could not be detected using existing screening and traditional sequencing methods all requiring prior knowledge of exact sequence of the suspected pathogen. Over 30,000 organ transplants are performed in the U.S. each year. Knowledge of the genetic sequence of this virus might enable improvements in screening that will enhance the safety of transplantation.
454 Life Sciences develops and commercializes the innovative Genome Sequencer™ system for ultra-high-throughput DNA sequencing. Specific applications include de novo sequencing and re-sequencing of genomes, metagenomics, RNA analysis, and targeted sequencing of DNA regions of interest. The hallmarks of 454 Sequencing™ are its simple, unbiased sample preparation and long, highly accurate sequence reads, including paired reads. 454 Sequencing technology has enabled many peer-reviewed studies in diverse research fields such as cancer and infectious disease research, drug discovery, marine biology, anthropology, paleontology and many more.