Interakce viru a hostitelské buňky: příklady z kontroly gamaretrovirové transkripce a cílení somatických hypermutací pomocí SV40 enhanceru

Slavková, Martina

The coexistence of viruses and their host cells has given rise to an intricate web of interactions. Only with a good understanding of these interactions can we progress to smarter and more efficient deployment of viral properties in research and therapeutic fields. During their life cycle, retroviruses (RV) require integration of their genome into the host genome. The integration site is one of the factors determining RV expression and may also act negatively towards epigenetic silencing of the provirus and latency. The murine leukemia virus (MLV) was previously shown to be stably expressed upon integration into promoters and enhancers of active genes. Here we show that this long-term stability is not specific to MLV, but it is a general characteristic of gamma-RV. Most importantly, after they establish stable expression, they remain stably expressed even after integration retargeting and targeted insertions in the repressive environment of lamina-associated domains. Another example of virus-host interaction is the truncation of large T antigen (LTAg) of polyomaviruses caused by cytidine deamination-induced mutations. We showed that SV40 enhancer possesses somatic hypermutation (SHM) targeting activity and activation induced deaminase (AID)-induced SHM may lead to truncated LTAg. Such truncated...

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