title: Numerous conserved and divergent microRNAs expressed by herpes simplex viruses 1 and 2.
abstract: Certain viruses use microRNAs (miRNAs) to regulate the expression of their own genes, host genes, or both. Previous studies have identified a limited number of miRNAs expressed by herpes simplex viruses 1 and 2 (HSV-1 and -2), some of which are conserved between these two viruses. To more comprehensively analyze the miRNAs expressed by HSV-1 or HSV-2 during productive and latent infection, we applied a massively parallel sequencing approach. We were able to identify 16 and 17 miRNAs expressed by HSV-1 and HSV-2, respectively, including all previously known species, and a number of previously unidentified virus-encoded miRNAs. The genomic positions of most miRNAs encoded by these two viruses are within or proximal to the latency-associated transcript region. Nine miRNAs are conserved in position and/or sequence, particularly in the seed region, between these two viruses. Interestingly, we did not detect an HSV-2 miRNA homolog of HSV-1 miR-H1, which is highly expressed during productive infection, but we did detect abundant expression of miR-H6, whose seed region is conserved with HSV-1 miR-H1 and might represent a functional analog. We also identified a highly conserved miRNA family arising from the viral origins of replication. In addition, we detected several pairs of complementary miRNAs and we found miRNA-offset RNAs (moRs) arising from the precursors of HSV-1 and HSV-2 miR-H6 and HSV-2 miR-H4. Our results reveal elements of miRNA conservation and divergence that should aid in identifying miRNA functions.
authors.affiliation: Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, 250 Longwood Ave., Boston, MA 02115, USA.
authors.forename: Igor
authors.initials: I
authors.lastname: Jurak
authors.forename: Martha F
authors.initials: MF
authors.lastname: Kramer
authors.forename: Joseph C
authors.initials: JC
authors.lastname: Mellor
authors.forename: Alison L
authors.initials: AL
authors.lastname: van Lint
authors.forename: Frederick P
authors.initials: FP
authors.lastname: Roth
authors.forename: David M
authors.initials: DM
authors.lastname: Knipe
authors.forename: Donald M
authors.initials: DM
authors.lastname: Coen
mesh_terms: D000818:Animals; D002460:Cell Line; D002522:Chlorocebus aethiops; D017124:Conserved Sequence; D018259:Herpesvirus 1, Human / Q000502:physiology*; D018258:Herpesvirus 2, Human / Q000502:physiology*; D006801:Humans; D035683:MicroRNAs / Q000096:biosynthesis* / Q000235:genetics; D011110:Polymorphism, Genetic; D012367:RNA, Viral / Q000096:biosynthesis* / Q000235:genetics; D017422:Sequence Analysis, DNA
chemical_list: D035683:MicroRNAs; D012367:RNA, Viral