Comprehensive annotations of human herpesvirus 6A and 6B genomes reveal novel and conserved genomic features

Yaara Finkel, Dominik Schmiedel, Julie Tai-Schmiedel, Aharon Nachshon, Roni Winkler, Martina Dobesova, Michal Schwartz, Ofer Mandelboim, Noam Stern-Ginossar*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

25 Scopus citations


Human herpesvirus-6 (HHV-6) A and B are ubiquitous betaherpesviruses, infecting the majority of the human population. They encompass large genomes and our understanding of their protein coding potential is far from complete. Here, we employ ribosome-profiling and systematic transcript-analysis to experimentally define HHV-6 translation products. We identify hundreds of new open reading frames (ORFs), including upstream ORFs (uORFs) and internal ORFs (iORFs), generating a complete unbiased atlas of HHV-6 proteome. By integrating systematic data from the prototypic betaherpesvirus, human cytomegalovirus, we uncover numerous uORFs and iORFs conserved across betaherpesviruses and we show uORFs are enriched in late viral genes. We identified three highly abundant HHV-6 encoded long non-coding RNAs, one of which generates a non-polyadenylated stable intron appearing to be a conserved feature of betaherpesviruses. Overall, our work reveals the complexity of HHV-6 genomes and highlights novel features conserved between betaherpesviruses, providing a rich resource for future functional studies.

Original languageAmerican English
Article numbere50960
StatePublished - Jan 2020

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