Abstract

We propose a system for continuing surveillance of viral pathogens circulating in large human populations. We base this system on the physical isolation of viruses from large pooled samples of human serum and plasma (e.g., discarded specimens from diagnostic laboratories), followed by shotgun sequencing of the resulting genomes. The technology for concentrating virions from 100-L volumes was developed previously at Oak Ridge National Laboratory, and the means for purifying and concentrating virions from volumes in microliters have been developed recently. At the same time, marine virologists have developed efficient methods for concentrating, amplifying, and sequencing complex viral mixtures obtained from the ocean. Given this existing technology base, we believe an integrated, automated, and contained system for surveillance of the human “virome” can be implemented within 1 to 2 years. Such a system could monitor the levels of known viruses in human populations, rapidly detect outbreaks, and systematically discover novel or variant human viruses.

Highlights

  • We propose a system for continuing surveillance of viral pathogens circulating in large human populations

  • One would expect that a comprehensive survey of human viruses, defining what we might term the human “virome” would be, at least conceptually, even more straightforward

  • For a totally new agent, the estimated interval between initial infection and detailed characterization is variable and depends on the presence of unusual symptoms, the failure to identify a virus after using all available specific tests, the recognition of a unique problem, and, in the past, the ability to grow the agent in culture

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Summary

Introduction

We propose a system for continuing surveillance of viral pathogens circulating in large human populations. These samples would be pooled and processed by using available technology to isolate virus particles en masse, recover viral nucleic acids, produce amplified shotgun libraries, carry out shotgun sequencing of the mixture of viral genomes, and reconstruct these genomes in silico with the techniques originally developed to sequence the entire human genome from random fragments.

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