Transcription Pattern of Human Herpesvirus 8 Open Reading Frame K3 in Primary Effusion Lymphoma and Kaposi's Sarcoma

Rimessi, Paola; Bonaccorsi, Angela; Fabris, M.; Brocca-Cofano, Egidio; Caputo, Antonella; Melucci-Vigo, Gianna; Falchi, Mario; Cafaro, Aurelio; Cassai, Enzo; Ensoli, Barbara; Monini, Paolo

doi:10.1128/jvi.75.15.7161-7174.2001

Cited by 32 publications

(42 citation statements)

References 72 publications

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“…It is speculated that grouping specific genes into bi-or polycistronic transcripts allows KSHV to maximize its coding capacity and level of gene regulation (78,79). For example, splicing of one bicistronic mRNA that disrupts a large portion of the upstream ORF allows expression of the downstream protein (80). However, it is unknown what effect the lengthy 5= UTR of ALT has upon its downstream CDSs K14 and ORF74, and it is possible that K14 and ORF74 proteins are exclusively translated from the two splice isoforms of K14-ORF74 bicistronic transcripts.…”

Section: Discussionmentioning

confidence: 99%

Expression of the Antisense-to-Latency Transcript Long Noncoding RNA in Kaposi's Sarcoma-Associated Herpesvirus

Schifano

Corcoran

Kelkar

et al. 2017

J Virol

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The regulation of latency is central to herpesvirus biology. Recent transcriptome-wide surveys have uncovered evidence for promiscuous transcription across the entirety of the Kaposi's sarcoma-associated herpesvirus (KSHV) genome and postulated the existence of multiple viral long noncoding RNAs (lncRNAs). Nextgeneration sequencing studies are highly dependent on the specific experimental approach and particular algorithms of analysis and therefore benefit from independent confirmation of the results. The antisense-to-latency transcript (ALT) lncRNA was discovered by genome-tiling microarray (Chandriani et al., J Virol 86:7934 -7942, 2010, https://doi.org/10.1128/JVI.00645-10). To characterize ALT in detail, we physically isolated this lncRNA by a strand-specific hybrid capture assay and then employed transcriptome sequencing and novel reverse transcription-PCR (RT-PCR) assays to distinguish all RNA species in the KSHV latency region. These methods confirm that ALT initiates at positions 120739/121012 and encodes a single splice site, which is shared with the 3=-coterminal K14-vGPCR/ORF74 mRNA, terminating at 130873 (GenBank accession number GQ994935), resulting in an ϳ10,000-nucleotide transcript. No shorter ALT isoforms were identified. This study also identified a novel intron within the LANA 5= untranslated region using a splice acceptor at 127888. In summary, ALT joins PAN/nut1/T1.1 as a bona fide lncRNA of KSHV with potentially important roles in viral gene regulation and pathogenesis.IMPORTANCE Increasing data support the importance of noncoding RNAs (ncRNAs), including microRNAs (miRNAs) and lncRNAs, which have been shown to exert critical regulatory functions without coding for recognizable proteins. Defining the sequences of these ncRNAs is essential for future studies aiming to functionally characterize a specific ncRNA. Most lncRNA studies are highly dependent on high-throughput sequencing and bioinformatic analyses, few studies follow up on the initial predictions, and analyses are at times discordant. The manuscript characterizes one key viral lncRNA, ALT, by physically isolating ALT and by a sequencing-independent assay. It provides for a simple assay to monitor lncRNA expression in experimental and clinical samples. ALT is expressed antisense to the major viral latency transcripts encoding LANA as well as the viral miRNAs and thus has the potential to regulate this key part of the viral life cycle.

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Section: Discussionmentioning

confidence: 99%

Expression of the Antisense-to-Latency Transcript Long Noncoding RNA in Kaposi's Sarcoma-Associated Herpesvirus

Schifano

Corcoran

Kelkar

et al. 2017

J Virol

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“…K3 and K5 are both expressed in KS tissue in a lytic pattern, and K3 has been detected as part of a bicistronic transcript in a screen for IE gene expression in PEL cells (213,430). The K5 transcript expression is resistant to low, but not high, concentrations of CHX in PEL cells (212) but has not been detected as an IE product in subtractive screens (430,542).…”

Section: Orf16/vbcl-2mentioning

confidence: 99%

“…The K5 transcript expression is resistant to low, but not high, concentrations of CHX in PEL cells (212) but has not been detected as an IE product in subtractive screens (430,542).…”

Section: Orf16/vbcl-2mentioning

confidence: 99%

Molecular Genetics of Kaposi's Sarcoma-Associated Herpesvirus (Human Herpesvirus 8) Epidemiology and Pathogenesis

Dourmishev

Palmeri

et al. 2003

Microbiol Mol Biol Rev

309

367

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Kaposi's sarcoma had been recognized as unique human cancer for a century before it manifested as an AIDS-defining illness with a suspected infectious etiology. The discovery of Kaposi's sarcoma-associated herpesvirus (KSHV), also known as human herpesvirus-8, in 1994 by using representational difference analysis, a subtractive method previously employed for cloning differences in human genomic DNA, was a fitting harbinger for the powerful bioinformatic approaches since employed to understand its pathogenesis in KS. Indeed, the discovery of KSHV was rapidly followed by publication of its complete sequence, which revealed that the virus had coopted a wide armamentarium of human genes; in the short time since then, the functions of many of these viral gene variants in cell growth control, signaling apoptosis, angiogenesis, and immunomodulation have been characterized. This critical literature review explores the pathogenic potential of these genes within the framework of current knowledge of the basic herpesvirology of KSHV, including the relationships between viral genotypic variation and the four clinicoepidemiologic forms of Kaposi's sarcoma, current viral detection methods and their utility, primary infection by KSHV, tissue culture and animal models of latent- and lytic-cycle gene expression and pathogenesis, and viral reactivation from latency. Recent advances in models of de novo endothelial infection, microarray analyses of the host response to infection, receptor identification, and cloning of full-length, infectious KSHV genomic DNA promise to reveal key molecular mechanisms of the candidate pathogeneic genes when expressed in the context of viral infection

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“…Determining functional relationships between sets of coregulated genes is complicated by the presence of polycistronic transcription units, weak polyadenylation sites, alternative splicing, and so on. Primary transcripts arising from the ORF70 promoter extend to a polyadenylation site downstream of K3, and possibly farther (48). In addition to a 1.5-kb spliced IE mRNA, there are at least three different E mRNAs, of which only the 2.5-kb unspliced version retains the complete ORF70 open reading frame.…”

Section: Vol 84 2010 Csl Binding Sites In Many Kshv Promoters 1343mentioning

confidence: 99%

Wide-Scale Use of Notch Signaling Factor CSL/RBP-Jκ in RTA-Mediated Activation of Kaposi's Sarcoma-Associated Herpesvirus Lytic Genes

Persson

Wilson

2010

J Virol

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Transcription Pattern of Human Herpesvirus 8 Open Reading Frame K3 in Primary Effusion Lymphoma and Kaposi's Sarcoma

Abstract: Human herpesvirus 8 (HHV-8) is found in immunoblastic B cells of patients with multicentric

Cited by 32 publications

References 72 publications

Expression of the Antisense-to-Latency Transcript Long Noncoding RNA in Kaposi's Sarcoma-Associated Herpesvirus

Expression of the Antisense-to-Latency Transcript Long Noncoding RNA in Kaposi's Sarcoma-Associated Herpesvirus

Molecular Genetics of Kaposi's Sarcoma-Associated Herpesvirus (Human Herpesvirus 8) Epidemiology and Pathogenesis

Wide-Scale Use of Notch Signaling Factor CSL/RBP-Jκ in RTA-Mediated Activation of Kaposi's Sarcoma-Associated Herpesvirus Lytic Genes

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