Influence of ND10 Components on Epigenetic Determinants of Early KSHV Latency Establishment

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KSHV is the etiological agent of several cancers including Kaposi's sarcoma, one of the most frequent tumors in Sub-Saharan Africa. Since the proliferating cells in these cancers are latently infected with KSHV, there is an urgent need to elucidate the molecular basis underlying latency establishment. While it is well established that intricate histone modification patterns preserve the latent state, the mechanisms that lead to primary establishment of such patterns and subsequent formation of repressive heterochromatin remain largely unknown. During the last years, components of distinct nuclear compartments, so called ND10 or PML bodies, have emerged as modulators of viral chromatin and gene expression. Here, we present the first systematic analysis of the mutual influence between KSHV and ND10 components during the early infection phase. We find that latent KSHV infection dramatically alters the sub-nuclear distribution of the soluble form of a ND10 core protein termed Sp100. This relocalization likely serves to facilitate the recruitment of polycomb repressive complexes and formation of facultative heterochromatin, and we hence propose that soluble Sp100 is an antagonist of KSHV latency establishment. Our findings have important implications for the understanding of viral latency establishment and also provide valuable insight into cellular chromatin regulation pathways.

Vyšlo v časopise: Influence of ND10 Components on Epigenetic Determinants of Early KSHV Latency Establishment. PLoS Pathog 10(7): e32767. doi:10.1371/journal.ppat.1004274
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004274

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