抄録
Background: 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. Results: 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. Conclusion: 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.
| 元の言語 | English |
|---|---|
| 記事番号 | 204 |
| ジャーナル | BMC Genomics |
| 巻 | 19 |
| 発行部数 | 1 |
| DOI | |
| 出版物ステータス | Published - 20-03-2018 |
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All Science Journal Classification (ASJC) codes
- Biotechnology
- Genetics
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Comparative genomic, transcriptomic, and proteomic reannotation of human herpesvirus 6. / Greninger, Alexander L.; Knudsen, Giselle M.; Roychoudhury, Pavitra; Hanson, Derek J.; Sedlak, Ruth Hall; Xie, Hong; Guan, Jon; Nguyen, Thuy; Peddu, Vikas; Boeckh, Michael; Huang, Meei Li; Cook, Linda; Depledge, Daniel P.; Zerr, Danielle M.; Koelle, David M.; Gantt, Soren; Yoshikawa, Tetsushi; Caserta, Mary; Hill, Joshua A.; Jerome, Keith R.
：: BMC Genomics, 巻 19, 番号 1, 204, 20.03.2018.研究成果: Article
TY - JOUR
T1 - Comparative genomic, transcriptomic, and proteomic reannotation of human herpesvirus 6
AU - Greninger, Alexander L.
AU - Knudsen, Giselle M.
AU - Roychoudhury, Pavitra
AU - Hanson, Derek J.
AU - Sedlak, Ruth Hall
AU - Xie, Hong
AU - Guan, Jon
AU - Nguyen, Thuy
AU - Peddu, Vikas
AU - Boeckh, Michael
AU - Huang, Meei Li
AU - Cook, Linda
AU - Depledge, Daniel P.
AU - Zerr, Danielle M.
AU - Koelle, David M.
AU - Gantt, Soren
AU - Yoshikawa, Tetsushi
AU - Caserta, Mary
AU - Hill, Joshua A.
AU - Jerome, Keith R.
PY - 2018/3/20
Y1 - 2018/3/20
N2 - Background: 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. Results: 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. Conclusion: 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.
AB - Background: 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. Results: 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. Conclusion: 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.
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U2 - 10.1186/s12864-018-4604-2
DO - 10.1186/s12864-018-4604-2
M3 - Article
C2 - 29554870
AN - SCOPUS:85044245965
VL - 19
JO - BMC Genomics
JF - BMC Genomics
SN - 1471-2164
IS - 1
M1 - 204
ER -