Exploiting Viral Genomics to Understand Disease

Summary

Viruses are global pathogens that cause substantial morbidity and mortality in humans. Novel viruses jump into humans from animal host reservoirs, and these zoonotic events can lead to outbreaks, epidemics, and/or pandemics. Thus, the viral GCID projects are focused on significant endemic viral pathogens of humans, as well as viruses from animal hosts that have strong zoonotic potential. High-throughput whole-genome next-generation sequencing (NGS) and bioinformatics analyses will be performed for more than 8,000 viral strains representing five viral families, including NIAID priority pathogens. The characterization of their genetic diversity will improve our understanding of critical mechanisms central to viral evolution, pathogenesis, transmission, and antiviral resistance. Specifically, we aim to: 1) compare and contrast the genetic diversity and evolutionary dynamics of viruses circulating within and/or between humans and animal reservoirs, 2) elucidate viral-host-microbiome determinants that influence viral pathogenesis, and 3) perform deep NGS to understand intra-host viral diversity, transmission dynamics, and antiviral resistance.

The sequencing data will be analyzed using phylogenetics and other bioinformatics algorithms to show the spatial and temporal evolution of these pathogens. These data will help to identify, track, and predict antigenic drift/shift, recombination, escape from natural or vaccine-induced host immune responses, antiviral resistance, inter- and intra-species transmission, and the response of a host's commensal microbiota to viral infection. The information generated from these studies will help us produce superior vaccines and antivirals and are critical for rapid responses to the emergence of novel pathogens (i.e., pandemic preparedness) that arise naturally or as a result of bioterrorism.

Supplemental Projects

  • Chikungunya virus complete-genome sequencing from the Americas to understand its emergence, evolutionary dynamics, and signatures of virulence.
  • A high throughput approach to screen and sequence human samples suspected to be Zika virus positive
  • Definition and characterization of the MHC region and MHC diversity in ferrets used for biomedical research





JCVI viral sequencing pipeline: 1) receipt and tracking of specimens, 2) nucleic acid preparation, 3) viral genomic amplification/enrichment, 4) barcoding genomes of individual samples, 5) library construction from a pool of barcoded amplicons, 6) high-throughput sequencing using Illumina MiSeq or HISeq2000 and/or Life Technologies Ion Torrent PGM platforms, 6) deconvolution of barcoded samples, 7) genome assembly, 8) automated bioinformatics analysis, and 9) submission of assembled sequences, associated raw data, and metadata to appropriate databases (e.g., NCBI, ViPR, IRD).

Citations

All Publications that use data generated and/or are supported by the Sequencing Center at JCVI should acknowledge the sponsor as below:

"Research reported in this publication was supported by the National Institute Of Allergy And Infectious Diseases of the National Institutes of Health under Award Number U19AI110819. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health."