PMID- 22114334 OWN - NLM STAT- MEDLINE DCOM- 20120409 LR - 20231115 IS - 1098-5514 (Electronic) IS - 0022-538X (Print) IS - 0022-538X (Linking) VI - 86 IP - 3 DP - 2012 Feb TI - Small RNA deep sequencing identifies microRNAs and other small noncoding RNAs from human herpesvirus 6B. PG - 1638-49 LID - 10.1128/JVI.05911-11 [doi] AB - Roseolovirus, or human herpesvirus 6 (HHV-6), is a ubiquitous human pathogen infecting over 95% of the population by the age of 2 years. As with other herpesviruses, reactivation of HHV-6 can present with severe complications in immunocompromised individuals. Recent studies have highlighted the importance of herpesvirus-derived microRNAs (miRNAs) in modulating both cellular and viral gene expression. An initial report which computed the likelihood of various viruses to encode miRNAs did not predict HHV-6 miRNAs. To experimentally screen for small HHV-6-encoded RNAs, we conducted large-scale sequencing of Sup-T-1 cells lytically infected with a laboratory strain of HHV-6B. This revealed an abundant, 60- to 65-nucleotide RNA of unknown function derived from the lytic origin of replication (OriLyt) that gave rise to smaller RNA species of 18 or 19 nucleotides. In addition, we identified four pre-miRNAs whose mature forms accumulated in Argonaute 2. In contrast to the case for other betaherpesviruses, HHV-6B miRNAs are expressed from direct repeat regions (DR(L) and DR(R)) located at either side of the genome. All miRNAs are conserved in the closely related HHV-6A variant, and one of them is a seed ortholog of the human miRNA miR-582-5p. Similar to alphaherpesvirus miRNAs, they are expressed in antisense orientation relative to immediate-early open reading frames (ORFs) and thus have the potential to regulate key viral genes. FAU - Tuddenham, Lee AU - Tuddenham L AD - Architecture et Reactivite de l'ARN, Universite de Strasbourg, Institut de Biologie Moleculaire et Cellulaire du CNRS, Strasbourg, France. FAU - Jung, Jette S AU - Jung JS FAU - Chane-Woon-Ming, Beatrice AU - Chane-Woon-Ming B FAU - Dolken, Lars AU - Dolken L FAU - Pfeffer, Sebastien AU - Pfeffer S LA - eng GR - 260767/ERC_/European Research Council/International GR - G1002523/MRC_/Medical Research Council/United Kingdom PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20111123 PL - United States TA - J Virol JT - Journal of virology JID - 0113724 RN - 0 (DNA Primers) RN - 0 (MicroRNAs) RN - 0 (RNA, Untranslated) SB - IM MH - Base Sequence MH - Cell Line MH - DNA Primers MH - Fluorescent Antibody Technique MH - Genes, Viral MH - Herpesvirus 6, Human/*genetics MH - Humans MH - Likelihood Functions MH - MicroRNAs/*genetics MH - RNA, Untranslated/*genetics MH - Replication Origin MH - Reverse Transcriptase Polymerase Chain Reaction PMC - PMC3264354 EDAT- 2011/11/25 06:00 MHDA- 2012/04/10 06:00 PMCR- 2012/08/01 CRDT- 2011/11/25 06:00 PHST- 2011/11/25 06:00 [entrez] PHST- 2011/11/25 06:00 [pubmed] PHST- 2012/04/10 06:00 [medline] PHST- 2012/08/01 00:00 [pmc-release] AID - JVI.05911-11 [pii] AID - 5911-11 [pii] AID - 10.1128/JVI.05911-11 [doi] PST - ppublish SO - J Virol. 2012 Feb;86(3):1638-49. doi: 10.1128/JVI.05911-11. Epub 2011 Nov 23.