title: Identification of two small RNAs within the first 1.5-kb of the herpes simplex virus type 1-encoded latency-associated transcript.
abstract: The herpes simplex virus type 1 (HSV-1) latency-associated transcript (LAT) is abundantly expressed in latently infected neurons. In the rabbit or mouse ocular models of infection, expression of the first 1.5 kb of LAT coding sequences is sufficient for and necessary for wild-type levels of spontaneous reactivation from latency. The antiapoptosis functions of LAT, which maps to the same 1.5 kb of LAT, are important for the latency-reactivation cycle because replacement of LAT with other antiapoptosis genes (the baculovirus IAP gene or the bovine herpesvirus type 1 latency-related gene) restores wild-type levels of reactivation to a LAT null mutant. A recent study identified a micro-RNA within LAT that can inhibit apoptosis (Gupta et al, Nature 442: 82-85). In this study, the authors analyzed the first 1.5 kb of LAT for additional small RNAs that may have regulatory functions. Two LAT-specific small RNAs were detected in productively infected human neuroblastoma cells within the first 1.5 kb of LAT, in a region that is important for inhibiting apoptosis. Although these small RNAs possess extensive secondary structure and a stem-loop structure, bands migrating near 23 bases were not detected suggesting these small RNAs are not true micro-RNAs. Both of the small LAT-specific RNAs have the potential to base pair with the ICP4 mRNA. These two small LAT RNAs may play a role in the latency-reactivation cycle by reducing apoptosis and/or by reducing ICP4 RNA expression.
authors.affiliation: Department of Veterinary and Biomedical Sciences, Nebraska Center for Virology, University of Nebraska, Lincoln, Nebraska 68503, USA.
authors.forename: Weiping
authors.initials: W
authors.lastname: Peng
authors.forename: Olga
authors.initials: O
authors.lastname: Vitvitskaia
authors.forename: Dale
authors.initials: D
authors.lastname: Carpenter
authors.forename: Steven L
authors.initials: SL
authors.lastname: Wechsler
authors.forename: Clinton
authors.initials: C
authors.lastname: Jones
mesh_terms: D017209:Apoptosis; D001483:Base Sequence; D045744:Cell Line, Tumor / Q000166:cytology / Q000821:virology; D003001:Cloning, Molecular; D015967:Gene Expression Regulation, Viral; D005814:Genes, Viral; D018259:Herpesvirus 1, Human / Q000235:genetics* / Q000502:physiology; D006801:Humans; D035683:MicroRNAs; D008969:Molecular Sequence Data; D009447:Neuroblastoma / Q000473:pathology; D009690:Nucleic Acid Conformation; D009693:Nucleic Acid Hybridization; D022661:RNA, Untranslated / Q000737:chemistry / Q000235:genetics* / Q000302:isolation & purification / Q000502:physiology; D012367:RNA, Viral / Q000737:chemistry / Q000235:genetics* / Q000302:isolation & purification / Q000502:physiology; D016415:Sequence Alignment; D014764:Viral Proteins / Q000235:genetics*; D014775:Virus Activation / Q000235:genetics*; D017735:Virus Latency / Q000235:genetics*
chemical_list: D035683:MicroRNAs; D022661:RNA, Untranslated; D012367:RNA, Viral; D014764:Viral Proteins; C477253:latency associated transcript, herpes simplex virus-1