Given that the NF-κB and NFAT5 binding motifs overlap, how do NF-κB and NFAT5 function at this overlapping or shared site in the LTR to drive viral transcription in response to MTb infection? Because NFAT5 expression continues to rise for at least 48 hours post-MTb infection (Figure 2A), one possibility is that the host factors NF-κB and NFAT5 associate with the LTR at different stages after viral activation. While NF-κB presence in the nucleus declines in the hours post MTb infection [74], [75], NFAT5 levels escalate. Thus, NFAT5, which is pivotal for HIV-1 transcription in unstimulated cells [31], may, after Mtb infection, perpetuate viral transcriptional initiation begun by NF-κB and, with Tat levels also elevated, promote high levels of sustained HIV-1 transcription. Indeed, in response to hypertonic stress, NFAT5 binds to the aldose reductase (AR) promoter and induces rapid hyperacetylation of histones H3 and H4 [76]. Furthermore, hypertonic stress of mouse renal collecting duct epithelial cells results in NFAT5 and NF-κB complex formation at NF-κB-dependent gene promoters [77]. Thus, there are precedents for imagining that NFAT5 could function at the HIV-1 LTR by inducing histone remodeling in a manner similar to NF-κB ([69], reviewed in [68], [70]) or by directly interacting with NF-κB in a cooperative manner.