Discovery of several thousand highly diverse circular DNA viruses

Author:

Tisza Michael J1,Pastrana Diana V1ORCID,Welch Nicole L1,Stewart Brittany1,Peretti Alberto1,Starrett Gabriel J1,Pang Yuk-Ying S1,Krishnamurthy Siddharth R2,Pesavento Patricia A3,McDermott David H4,Murphy Philip M4,Whited Jessica L567ORCID,Miller Bess56ORCID,Brenchley Jason8,Rosshart Stephan P9,Rehermann Barbara9,Doorbar John10,Ta'ala Blake A11,Pletnikova Olga12,Troncoso Juan C12,Resnick Susan M13,Bolduc Ben14,Sullivan Matthew B1415,Varsani Arvind1617ORCID,Segall Anca M18,Buck Christopher B1ORCID

Affiliation:

1. Lab of Cellular Oncology, National Cancer Institute, National Institutes of Health, Bethesda, United States

2. Metaorganism Immunity Section, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, United States

3. Department of Pathology, Microbiology, and Immunology, University of California, Davis, Davis, United States

4. Molecular Signaling Section, Laboratory of Molecular Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, United States

5. Department of Orthopedic Surgery, Harvard Medical School, The Harvard Stem Cell Institute, Brigham and Women's Hospital, Boston, United States

6. Broad Institute of MIT and Harvard, Cambridge, United States

7. Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, United States

8. Barrier Immunity Section, Lab of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Cambridge, United States

9. Immunology Section, Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, United States

10. Department of Pathology, University of Cambridge, Cambridge, United Kingdom

11. Mililani Mauka Elementary, Mililani, United States

12. Department of Pathology (Neuropathology), Johns Hopkins University School of Medicine, Baltimore, United States

13. Laboratory of Behavioral Neuroscience, National Institute on Aging, National Institutes of Health, Baltimore, United States

14. Department of Microbiology, Ohio State University, Columbus, United States

15. Civil Environmental and Geodetic Engineering, Ohio State University, Columbus, United States

16. The Biodesign Center of Fundamental and Applied Microbiomics, School of Life Sciences, Center for Evolution and Medicine, Arizona State University, Tempe, United States

17. Structural Biology Research Unit, Department of Clinical Laboratory Sciences, University of Cape Town, Rondebosch, South Africa

18. Viral Information Institute and Department of Biology, San Diego State University, San Diego, United States

Abstract

Although millions of distinct virus species likely exist, only approximately 9000 are catalogued in GenBank's RefSeq database. We selectively enriched for the genomes of circular DNA viruses in over 70 animal samples, ranging from nematodes to human tissue specimens. A bioinformatics pipeline, Cenote-Taker, was developed to automatically annotate over 2500 complete genomes in a GenBank-compliant format. The new genomes belong to dozens of established and emerging viral families. Some appear to be the result of previously undescribed recombination events between ssDNA and ssRNA viruses. In addition, hundreds of circular DNA elements that do not encode any discernable similarities to previously characterized sequences were identified. To characterize these ‘dark matter’ sequences, we used an artificial neural network to identify candidate viral capsid proteins, several of which formed virus-like particles when expressed in culture. These data further the understanding of viral sequence diversity and allow for high throughput documentation of the virosphere.

Funder

National Cancer Institute

Publisher

eLife Sciences Publications, Ltd

Subject

General Immunology and Microbiology,General Biochemistry, Genetics and Molecular Biology,General Medicine,General Neuroscience

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