The Lautenberg Center for General and Tumor Immunology, Institute for Medical Research Israel-Canada, The Hebrew University Hadassah Medical School, Jerusalem, Israel
Julie Tai-Schmiedel
Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel
Aharon Nachshon
Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel
Roni Winkler
Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel
Martina Dobesova
Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel
The Lautenberg Center for General and Tumor Immunology, Institute for Medical Research Israel-Canada, The Hebrew University Hadassah Medical School, Jerusalem, Israel
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.
