Abstract
Non-Sanger-based novel nucleic acid sequencing techniques, referred to as Next-Generation Sequencing (NGS), provide a rapid, reliable, high-throughput, and massively parallel sequencing methodology that has improved our understanding of human cancers and cancer-related viruses. NGS has become a quintessential research tool for more effective characterization of complex viral and host genomes through its ever-expanding repertoire, which consists of whole-genome sequencing, whole-transcriptome sequencing, and whole-epigenome sequencing. These new NGS platforms provide a comprehensive and systematic genome-wide analysis of genomic sequences and a full transcriptional profile at a single nucleotide resolution. When combined, these techniques help unlock the function of novel genes and the related pathways that contribute to the overall viral pathogenesis. Ongoing research in the field of virology endeavors to identify the role of various underlying mechanisms that control the regulation of the herpesvirus biphasic lifecycle in order to discover potential therapeutic targets and treatment strategies. In this review, we have complied the most recent findings about the application of NGS in Kaposi’s sarcoma-associated herpesvirus (KSHV) biology, including identification of novel genomic features and whole-genome KSHV diversities, global gene regulatory network profiling for intricate transcriptome analyses, and surveying of epigenetic marks (DNA methylation, modified histones, and chromatin remodelers) during de novo, latent, and productive KSHV infections.
Highlights
The most recently discovered human tumor virus, Kaposi’s sarcoma-associated herpesvirus (KSHV), or human herpesvirus 8 (HHV-8), is a γ2-lymphotropic-oncogenic virus that causes life-long persistent infection in humans
The latent to lytic switch of KSHV is regulated by the replication and transcription activator (RTA), a 110 kDa protein, encoded by the ORF50 gene, which is capable of inducing the cascade of lytic gene expression
Along with other significant discoveries, including the detection of a new unknown murine leukemia virus infection and the identification of cellular cytokine regulators disrupted by virus integration, global assessment of the KSHV transcriptome in the primary effusion lymphoma (PEL)-derived BCP-1 cell line indicated that viral immune signaling genes in the left cluster of the genome, such as K2/vIL-6, K4/vIL-8, and K5/E2-ubiquitin ligase 1, showed higher expression values of 840 FPKMs, 145 FPKMs, and 351 FPKMs, respectively, when compared to a latency-associated nuclear antigen (LANA)-containing rightward cluster with an expression value of 39 FPKMs; this suggests that secreted cytokines have a significant impact on both latent and lytic KSHV-infected cells [80]
Summary
The most recently discovered human tumor virus, Kaposi’s sarcoma-associated herpesvirus (KSHV), or human herpesvirus 8 (HHV-8), is a γ2-lymphotropic-oncogenic virus that causes life-long persistent infection in humans It is a major cause of AIDS-defining malignancies worldwide [1]. The major impact of the genome technology revolution is that it has enabled the analysis of cancer genome sequences and the genome structure and the elucidation of mechanisms of cancer pathogenesis, leading to improved tumor diagnosis and treatment. These novel digital NGS methods have provided greater speed, sensitivity, and resolution at a considerably lower per-base cost over other traditional sequencing methods.
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