HIV 1 Tat induces cell type specific expression of host genes in B cells

Анотація

In European countries and North America, high rates of Burkitt lymphoma are found preferentially among patients infected with HIV. Interestingly, HIV is mostly associated with B cell lymphomas although it does not infect B cells. Oncogenesis in HIV infected patients may be connected with the action of a small viral protein Tat, which is able to exit infected T cells and enter other cells via its cell¬penetrating domain. As Tat affects expression of host cell genes, we hypothesized that Tat protein could affect expression of B cell genes; this could trigger lymphomagenesis in HIV infected patients. To analyze the effect of HIV 1 Tat, we developed B cell lines ectopically expressing Tat protein. To discover genes that are regulated by Tat, total RNA was collected and RNA seq-based differential expression analysis was performed. We identified six KEGG pathways affected by Tat including virus response, cytokine cytokine receptor interaction pathway, ubiquitin mediated proteolysis pathway. Unexpectedly, when comparing genes modulated by Tat in B cells with those deregulated by Tat in T cells, we observed just a small overlap between the two sets. In conclusion, Tat protein appears to behave differently in B cells and T cells, exploiting distinct mechanisms to generate a specificenvironment in different tissues. The work was supported by Russian science foundation (project№ 17 -75- 20199).