TLR8 Activates HIV from Latently Infected Cells of Myeloid-Monocytic Origin Directly via the MAPK Pathway and from Latently Infected CD4+ T Cells Indirectly via TNF-α

摘要: We previously showed that the TLR7/8 agonist, R-848, activated HIV from cells of myeloid-monocytic origin. In this work, we show effect was solely due to triggering TLR8 and NF-κB involved in TLR8-mediated activation latently infected Inhibition Erk1/2 or p38α resulted attenuation NF-κB. Western blots confirmed but, surprisingly, not JNK. Although inhibitors a less attenuated response than did inhibitors, they had more pronounced on blocking replication, indicating other transcription factors controlled by are cells. TNF-α, which secreted subsequent triggering, contributed an autocrine manner, revealing bimodal mechanism can be sustained. also found TNF-α myeloid dendritic acted paracrine manner neighboring CD4 + T cells, do express TLR8. Notably, monocytes highly active antiretroviral therapy-treated patients with suppressed RNA robust secretion agonists, pointing functional signaling axis infection. Thus, represents very promising strategy for attacking silent its reservoir treated successfully therapy.