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.
N1 - Funding Information:
Mass spectrometry analysis was provided by the UCSF Mass Spectrometry Facility directed by Al Burlingame, supported by the Adelson Medical Research Foundation. We appreciate assistance from Alex Yamana, Gabby Dolgonos and Krithika Nathamuni for careful inspection of peptide mass spectral assignments. We thank Samia Naccache, Nicole Lieberman, Jesse Bloom for helpful comments on the manuscript.
Publisher Copyright:
© 2018 The Author(s).
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 -