Cotranscriptional Chromatin Remodeling by Small RNA Species: An HTLV-1 Perspective

Figure 1

The interaction between HTLV-1 infection pathway and miRNA pathways. HTLV-1 infection begins with viral gp46 and gp21 envelop proteins recognizing and binding receptors on target cell membrane followed by envelop fusion and receptor-mediated endocytosis. Once inside the cell, HTLV-1 loses its capsid and releases the single-stranded (+) ve sense RNA into the cytoplasm that undergoes reverse transcription to (−) ve sense DNA. A second DNA strand is then formed; the two strands form a helix, enter the nucleus, and integrate with the host genome forming the proviral particle. Transcription ensues with cellular pol II, CREB, CBP, p300, P/CAF, and viral Tax assembling at the 5^′LTR of the promoter region. This leads to Tax-dependent transcription of viral mRNA, transport of mRNA into the cytoplasm and its subsequent translation on ribosomes. The continuous green arrows indicate the HTLV-1 infection pathway, while the orange arrows indicate the miRNA biogenesis and mechanism of action pathway. The discontinuous blue arrows indicate points at which viral proteins might interact with the miRNA pathway and also where miRNA might interfere with viral transcription. Chromatin remodeling is one of the interfering mechanisms that can be brought about by siRNA direct binding of siRNA coupled with the RISC complex to DNA, methylation of heterochromatin regions of the chromosome, or modification of histone proteins associated with chromatin.