The HTLV-1 HBZ protein interacts with the SWI/SNF component Brg1 and suppresses viral gene expression

The human T cell leukemia virus type 1 (HTLV-1) regulatory proteins Tax1 and HBZ play key, sometimes opposing roles, in regulating viral and cellular gene expression. Previous studies have shown that through their interactions with CREB/CBP, Tax1 activates while HBZ inhibits transcription from the HTLV-1 LTR. In addition to CREB/CBP, Tax1 also regulates viral transcription by recruiting the SWI/SNF chromatin remodelling complexes to the viral promoter. Tax1 was shown to interact with SWI/SNF components Brg1, BAF53, BAF57, BAF155. Importantly Brg1 co-elutes with Tax1 and components of the basal transcription machinery such as PolI, CBP/P300 suggesting that both SWI/SNF and CREB/p300 are involved in Tax1 mediated transactivation of the LTR. Our previous studies using the yeast two hybrid system show that HBZ interacts with Brg1 suggesting that HBZ/Brg1 interactions may also play a role in the regulation of HTLV-1 viral gene expression. In this study we sought to further investigate the physical interaction between HBZ and Brg1 and determine its effect on Tax1 mediated LTR activation. Results Using co immunoprecipitation assays we show that HBZ interacts with full length Brg1 and our deletion studies show that the HSA domain of Brg1 is involved in this interaction. We show that HTLV-1 infected cell lines and ATL cells express high levels of Brg1 compared to the HTLV-2 infected cell line or uninfected cells. Interestingly we show that Tax1 enhances and stabalizes the expression of exogenous and endogenous Brg1. Moreover we show that HBZ substantially repesses HTLV-1 LTR activation by Tax1/Brg1 in a dose dependent manner. Conclusions Overall our findings show that in addition to inhibiting Tax1 mediated activation of the HTLV LTR via the CREB pathway, HBZ also inhibits viral gene expression via the SWI/SNF pathway which may have a profound overall effect on viral silencing and foster viral latency.