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.
journal_name
BMC Genomicsjournal_title
BMC genomicsauthors
Greninger AL,Knudsen GM,Roychoudhury P,Hanson DJ,Sedlak RH,Xie H,Guan J,Nguyen T,Peddu V,Boeckh M,Huang ML,Cook L,Depledge DP,Zerr DM,Koelle DM,Gantt S,Yoshikawa T,Caserta M,Hill JA,Jerome KRdoi
10.1186/s12864-018-4604-2subject
Has Abstractpub_date
2018-03-20 00:00:00pages
204issue
1issn
1471-2164pii
10.1186/s12864-018-4604-2journal_volume
19pub_type
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