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Background: Dicer, Ago2 and TRBP are the minimum components of the human RNA-induced silencing complex (RISC). While Dicer and Ago2 are RNases, TRBP is the double-stranded RNA binding protein (dsRBP) that loads small interfering RNA into the RISC. TRBP binds directly to Dicer through its C-terminal domain.

BackgroundAlthough indirect evidence suggests the male genital tract as a possible source of persistent HIV shedding in semen during antiretroviral therapy, this phenomenon is poorly understood due to the difficulty of sampling semen-producing organs in HIV+ asymptomatic individuals.Methodology/Principal FindingsUsing a range of molecular and cell biological techniques, this study investigates SIV infection within reproductive organs of macaques during the acute and chronic stages of the disease. We demonstrate for the first time the presence of SIV in the testes, epididymides, prostate and seminal vesicles as early as 14 days post-inoculation. This infection persists throughout the chronic stage and positively correlates with blood viremia. The prostate and seminal vesicles appear to be the most efficiently infected reproductive organs, followed by the epididymides and testes. Within the male genital tract, mostly T lymphocytes and a small number of germ cells harbour SIV antigens and RNA. In contrast to the other organs studied, the testis does not display an immune response to the infection. Testosteronemia is transiently increased during the early phase of the infection but spermatogenesis remains unaffected.Conclusions/SignificanceThe present study reveals that SIV infection of the macaque male genital tract is an early event and that semen-producing organs display differential infection levels and immune responses. These results help elucidate the origin of HIV in semen and constitute an essential base to improving the design of antiretroviral therapies to eradicate virus from semen.

SUMMARY The TAR RNA binding protein (TRBP) has emerged as a key player in many cellular processes. First identified as a cellular protein that facilitates the replication of human immunodeficiency virus, TRBP has since been shown to inhibit the activation of protein kinase R (PKR), a protein involved in innate immune responses and the cellular response to stress. It also binds to the PKR activator PACT and regulates its function. TRBP also contributes to RNA interference as an integral part of the minimal RNA-induced silencing complex with Dicer and Argonaute proteins. Due to its multiple functions in the cell, TRBP is involved in oncogenesis when its sequence is mutated or its expression is deregulated. The depletion or overexpression of TRBP results in malignancy, suggesting that the balance of TRBP expression is key to normal cellular function. These studies show that TRBP is multifunctional and mediates cross talk between different pathways. Its activities at the molecular level impact the cellular function from normal development to cancer and the response to infections.