Marek's disease virus latency-associated transcripts belong to a family of spliced RNAs that are antisense to the ICP4 homolog gene

Abstract

Marek's disease virus (MDV) latency-associated transcripts include at least two MDV small RNAs (MSRs) and a 10-kb RNA which map antisense to the ICP4 homolog gene and are relatively abundant in MDVtransformed lymphoblastoid cells. This report further describes the biological and structural properties of these RNAs. First, these RNAs were detected in primary lymphomas isolated from chickens infected with several oncogenic MDV strains. Second, the MSRs are nonpolyadenylated, whereas, the 10-kb RNA is predominantly polyadenylated. Third, MSRs localize to the nuclei of both lymphoblastoid cells and cytolytically infected chicken embryo fibroblasts. Fourth, the 3-region splice junctions of the MSRs during latent and productive infection were determined by sequencing RNA-PCR products generated with primers that flank the 3 splice region. The MSRs contain at least three introns, the largest of which overlaps the ICP4 putative translational start site. Fifth, the 5 end of the MSRs initiates approximately 5 kb upstream from the main body of the RNA. The extreme 5 exon is approximately 251 nucleotides (nt) long and is joined to the main body of the transcript upon removal of a 4,852-nt intron. Finally, the 10-kb RNA lies entirely within the repeats flanking the unique short region of the genome. We believe that the MSRs and 10-kb RNA belong to a family of spliced RNAs that map antisense to the ICP4 gene and comprise a complex transcriptional unit expressed during MDV-induced T-cell transformation.

A viral function represses accumulation of transcripts from productive-cycle genes in mouse ganglia latently infected with herpes simplex virus

“…Thus, most Anti-4 molecules could be long LAT species that are 0.01 to 0.02% as abundant as the major LATs. This would be akin to the long LATs encoded by Marek's disease virus that are antisense to transcripts encoding a homolog of ICP4 recently reported by Cantello et al (9). HSV LAT species antisense to the 3Ј end of ICP4 RNA have been detected during HSV latency by in situ hybridization (43), but none has yet been reported to extend across the sequences used to detect Anti-4.…”

The Transcriptional Landscape of Marek’s Disease Virus in Primary Chicken B Cells Reveals Novel Splice Variants and Genes

“…Here, we observed excessive splicing antisense to ICP4. These transcripts are part of the latency associated transcript (LAT) region, have a complex splice pattern, and their functions remain largely unknown [68,69]. Some of these RNAs function as MDV-encoded micro RNAs and are described elsewhere [70,71].…”

DNA from Dust: Comparative Genomics of Large DNA Viruses in Field Surveillance Samples

“…ICP4 is an important immediate-early protein in all herpesviruses, where it serves as a major regulator of viral transcription ( 42 – 44 ). The role of ICP4 in MDV pathogenesis is also considered crucial because of its proximity to the latency-associated transcripts (LATs) and recently described miRNAs ( 44 – 46 ). In a previous study of MDV-1 attenuation through serial passage in vitro , mutations in ICP4 appeared to coincide with attenuation ( 31 ).…”

“…For the viral transactivation protein ICP4, we explored the penetrance of a polymorphic locus (nucleotide position 5495) both in full-length genomes and also via targeted sequencing over time. Most of the work on this region in the MDV-1 genome has actually focused on the LATs that lie antisense to the ICP4 gene ( 44 , 45 ). This polymorphic locus could thus impact either ICP4’s coding sequence (aa 1832 serine versus tyrosine) or the sequence of the LATs.…”