A cluster of latently expressed genes in Kaposi's sarcoma-associated herpesvirus.
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.
Dittmer
D
D
Department of Microbiology and Immunology, University of California San Francisco, San Francisco, California 94143-0414, USA.
Lagunoff
M
M
Renne
R
R
Staskus
K
K
Haase
A
A
Ganem
D
D
D017398:Alternative Splicing; D001483:Base Sequence; D017931:DNA Primers; D004279:DNA, Viral; D017930:Genes, Reporter; D005814:Genes, Viral; D019288:Herpesvirus 8, Human / Q000235:genetics*; D017403:In Situ Hybridization; D005810:Multigene Family; D016366:Open Reading Frames; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics; D014158:Transcription, Genetic
D017931:DNA Primers; D004279:DNA, Viral; D012333:RNA, Messenger