Title |
Comparative genomic, transcriptomic, and proteomic reannotation of human herpesvirus 6
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Published in |
BMC Genomics, March 2018
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DOI | 10.1186/s12864-018-4604-2 |
Pubmed ID | |
Authors |
Alexander L. Greninger, Giselle M. Knudsen, Pavitra Roychoudhury, Derek J. Hanson, Ruth Hall Sedlak, Hong Xie, Jon Guan, Thuy Nguyen, Vikas Peddu, Michael Boeckh, Meei-Li Huang, Linda Cook, Daniel P. Depledge, Danielle M. Zerr, David M. Koelle, Soren Gantt, Tetsushi Yoshikawa, Mary Caserta, Joshua A. Hill, Keith R. Jerome |
Abstract |
Human herpesvirus-6A and -6B (HHV-6) are betaherpesviruses that reach > 90% seroprevalence in the adult population. Unique among human herpesviruses, HHV-6 can integrate into the subtelomeric regions of human chromosomes; when this occurs in germ line cells it causes a condition called inherited chromosomally integrated HHV-6 (iciHHV-6). Only two complete genomes are available for replicating HHV-6B, leading to numerous conflicting annotations and little known about the global genomic diversity of this ubiquitous virus. Using a custom capture panel for HHV-6B, we report complete genomes from 61 isolates of HHV-6B from active infections (20 from Japan, 35 from New York state, and 6 from Uganda), and 64 strains of iciHHV-6B (mostly from North America). HHV-6B sequence clustered by geography and illustrated extensive recombination. Multiple iciHHV-6B sequences from unrelated individuals across the United States were found to be completely identical, consistent with a founder effect. Several iciHHV-6B strains clustered with strains from recent active pediatric infection. Combining our genomic analysis with the first RNA-Seq and shotgun proteomics studies of HHV-6B, we completely reannotated the HHV-6B genome, altering annotations for more than 10% of existing genes, with multiple instances of novel splicing and genes that hitherto had gone unannotated. Our results are consistent with a model of intermittent de novo integration of HHV-6B into host germline cells during active infection with a large contribution of founder effect in iciHHV-6B. Our data provide a significant advance in the genomic annotation of HHV-6B, which will contribute to the detection, diversity, and control of this virus. |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
Unknown | 56 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
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Researcher | 13 | 23% |
Student > Master | 8 | 14% |
Student > Bachelor | 7 | 13% |
Student > Ph. D. Student | 6 | 11% |
Student > Postgraduate | 4 | 7% |
Other | 8 | 14% |
Unknown | 10 | 18% |
Readers by discipline | Count | As % |
---|---|---|
Medicine and Dentistry | 14 | 25% |
Biochemistry, Genetics and Molecular Biology | 9 | 16% |
Agricultural and Biological Sciences | 8 | 14% |
Engineering | 3 | 5% |
Immunology and Microbiology | 3 | 5% |
Other | 7 | 13% |
Unknown | 12 | 21% |