Open Collections

UBC Faculty Research and Publications

Comparative genomic, transcriptomic, and proteomic reannotation of human herpesvirus 6 Greninger, Alexander L; Knudsen, Giselle M; Roychoudhury, Pavitra; Hanson, Derek J; Sedlak, Ruth H; 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

Abstract

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.

Item Metadata

Title
Comparative genomic, transcriptomic, and proteomic reannotation of human herpesvirus 6
Creator
Greninger, Alexander L; Knudsen, Giselle M; Roychoudhury, Pavitra; Hanson, Derek J; Sedlak, Ruth H; 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
Contributor
Children's Hospital (Vancouver, B.C.)
Publisher
BioMed Central
Date Issued
2018-03-20
Description
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.
Subject
Herpesvirus; Human herpesvirus 6; HHV-6B; HHV-6A; Betaherpesvirus; Viral genomics; Herpesvirus genomics; Comparative genomics; Genomic annotation; iciHHV-6
Genre
Article
Type
Text
Language
eng
Date Available
2018-03-21
Provider
Vancouver : University of British Columbia Library
Rights
Attribution 4.0 International (CC BY 4.0)
DOI
10.14288/1.0364401
URI
http://hdl.handle.net/2429/64874
Affiliation
Other UBC; Non UBC
Citation
BMC Genomics. 2018 Mar 20;19(1):204
Publisher DOI
10.1186/s12864-018-4604-2
Peer Review Status
Reviewed
Scholarly Level
Faculty
Copyright Holder
The Author(s).
Rights URI
http://creativecommons.org/licenses/by/4.0/
Aggregated Source Repository
DSpace

Item Media

Item Citations and Data

Rights

Attribution 4.0 International (CC BY 4.0)