An overt genetic map of the KSHV genome in a classic KS specimen.

On 24 January, the international academic journal PLOS Pathogens published a research paper entitled Epigentic Landscape of Kaposi's sarcoma-associated herpesvirus genome in classic Kaposi's sarcoma tissues of the Lanke Research Group of the Pasteur Institute of the Chinese Academy of Sciences in Shanghai.
-related herpes virus (Kaposi's sarcoma associated herpesvirus, KSHV) belongs to the Gamma herpes virus family, with human Kaposi's sarcoma The occurrence of malignant tumors such as s sarcoma, KS), primary expedited lymphoma (Primary effusion lymphoma, PEL) and multicenter Castleman Disease (MCD) is closely related.
KSHV is a double-stranded DNA virus with a larger genome (about 170kb) encoded by more than 90 viral genes, which exhibit two distinct states of latent infection and lysation replication over their life cycle.
in the latent infection process, the vast majority of virus genes are silent, only a small number of viral gene expression.
mechanisms for establishing and maintaining latent infections with KSHV have not yet been fully clarified.
genetic modification is thought to be closely related to the expression regulation of viral genes.
In previous studies, by determining the exogenous genetic status of the viral genome in the in-body cultured KSHV-positive PEL cell line, the researchers established an exogenetic map of the KSHV genome, but the exogencic genetic status of the virus under clinical pathophysiological conditions is still unknown.
studies have reported that the expression patterns of KSHV latent states in KS are not exactly the same as PEL, and that KS lacks the cell line that can maintain the viral genome on behalf of its characteristics, so it is important to directly determine the prescient genetic state of the viral genome in KS tissue.
under the guidance of researcher Lanke, assistant researcher Sun Rui established a method that can directly use clinical KS specimens for chromatin immunosequencing-high-volume sequencing (ChIP-seq).
an eminomic genetic map of the KSHV genome in the classic KS specimen was established by measuring binding places in the KSHV virus genomic acetylation (AcH3) and methylation (H3K27me3) modified and latent-related nuclear antigen (LANA) genomes.
results show that the results of the classic KS transcription inhibitory H3K27me3 modification similar to the cell line are widely distributed on the KSHV genome, while the transcription-activated AcH3 modification shows different patterns, confined to the latent gene seat of the genome.
H3K27me3 modification, which is rich in the coding area of the viral interferon regulator 3 (vIRF3), confirms the silent state of vIRF3 in KS, which is significantly different from the situation in PEL.
LANA's rich collection of repeated sequences (TRs) at the end of the viral genome has also been confirmed in KS tissue samples, but its binding site on the host genome is significantly different from the results in the cell line.
transcription replication activator (RTA) is a key molecule that controls the KSHV life cycle, and the RTA initiator region has a large number of H3K27me3 modifications, consistent with previous results in cell line, but interestingly, a large number of riches in TR region AcH3 previously reported in cell line were not observed in KS tissue samples.
the KSHV genome surface genetic panorama established in KS tissue provides new clues for an in-depth understanding of the latent infection mechanism of KSHV in the host body, and lays an important foundation for future research and development of new treatments based on targeted surface genetics.
the study was supported by NSFC-NIH, NSFC-NIH, NSFC-R01, NSFC Key Projects and NIH R01.
Erle Robertson, a professor at the University of Pennsylvania in the United States, was the study's main collaborator.
Lei and Tan Xiaohua of Hangzhou Normal University Medical College provided clinical specimen support for the study.
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