A cluster of latently expressed genes in Kaposi's sarcoma-associated herpesvirus

J Virol. 1998 Oct;72(10):8309-15. doi: 10.1128/JVI.72.10.8309-8315.1998.

Abstract

Infection with Kaposi's sarcoma-associated herpesvirus (KSHV) is closely associated with Kaposi's sarcoma (KS) and primary effusion lymphoma, with viral genomes present in a latent state in the majority of tumor cells. Here we describe a cluster of latently expressed viral genes whose mRNAs are generated from a common promoter. Two mRNAs in this region encode the latency-associated nuclear antigen, the product of open reading frame 73 (ORF73). The larger RNA, of 5.8 kb, is an unspliced transcript that includes ORF72 and -71 at its 3' end; it initiates at nucleotides (nt) 127880 to 127886 from a promoter lacking recognizable TATA elements. A less abundant mRNA, of 5.4 kb, is a variant of this transcript, in which 336 nt of 5' noncoding information has been removed by RNA splicing. A third, more abundant RNA is generated from the same promoter region via splicing from the common splice donor at nt 127813 to an acceptor 5' to ORF72; this transcript is the presumed mRNA for ORF72, which encodes the viral cyclin D homolog. All three RNAs are 3' coterminal. In situ hybridization analysis with probes that can detect all three transcripts shows that the RNAs are detectable in a large fraction of BCBL-1 cells prior to lytic induction and in >70% of KS spindle cells in primary KS tumors. This confirms that these transcripts are indeed latent RNAs and suggests a role for their products in viral persistence and/or KSHV-associated proliferation.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Alternative Splicing
  • Base Sequence
  • DNA Primers
  • DNA, Viral
  • Genes, Reporter
  • Genes, Viral*
  • Herpesvirus 8, Human / genetics*
  • In Situ Hybridization
  • Multigene Family*
  • Open Reading Frames
  • Promoter Regions, Genetic
  • RNA, Messenger / genetics
  • Transcription, Genetic

Substances

  • DNA Primers
  • DNA, Viral
  • RNA, Messenger