HIV-1 Tat Promotes Kaposi's Sarcoma-Associated Herpesvirus (KSHV) vIL-6-Induced Angiogenesis and Tumorigenesis by Regulating PI3K/PTEN/AKT/GSK-3β Signaling Pathway

Kaposi's sarcoma (KS)-associated herpesvirus (KSHV) is etiologically associated with KS, the most common AIDS-related malignancy. KS is characterized by vast angiogenesis and hyperproliferative spindle cells. We have previously reported that HIV-1 Tat can trigger KSHV reactivation and accelerate Kaposin A-induced tumorigenesis. Here, we explored Tat promotion of KSHV vIL-6-induced angiogenesis and tumorigenesis. Tat promotes vIL-6-induced cell proliferation, cellular transformation, vascular tube formation and VEGF production in culture. Tat enhances vIL-6-induced angiogenesis and tumorigenesis of fibroblasts and human endothelial cells in a chicken chorioallantoic membrane (CAM) model. In an allograft model, Tat promotes vIL-6-induced tumorigenesis and expression of CD31, CD34, SMA, VEGF, b-FGF, and cyclin D1. Mechanistic studies indicated Tat activates PI3K and AKT, and inactivates PTEN and GSK-3β in vIL-6 expressing cells. LY294002, a specific inhibitor of PI3K, effectively impaired Tat's promotion of vIL-6-induced tumorigenesis. Together, these results provide the first evidence that Tat might contribute to KS pathogenesis by synergizing with vIL-6, and identify PI3K/AKT pathway as a potential therapeutic target in AIDS-related KS patients. © 2013 Zhou et al

Remission from Kaposi's sarcoma on HAART is associated with suppression of HIV replication and is independent of protease inhibitor therapy

Highly active antiretroviral therapy (HAART) reduces the incidence and improves the prognosis of Kaposi's sarcoma (KS). This study was designed to identify factors associated with KS clinical responses in HIV-infected patients during HAART. We reviewed the files of 138 HIV-1-infected patients with KS. Epidemiologic and HIV-related clinical and biological parameters were recorded at KS diagnosis (baseline) and every 6 months thereafter. In a subset of 73 antiretroviral-naive patients, we compared the clinical outcome of KS according to the use or nonuse of protease inhibitors (PI). After 6 months of follow-up, KS remission was more frequent in patients who were naive of HAART and who were at ACTG stage S0 at baseline (P=0.03 and 0.02). Undetectable HIV viral load was strongly associated with KS remission (P⩽0.004 at all time points), while CD4 cell count was not. Among the 73 antiretroviral-naive patients at baseline, and who were studied for 24 months, KS outcome did not differ between patients who were prescribed PI-containing and PI-sparing regimens. Intercurrent multicentric Castleman's disease was associated with poor outcome after 60 months of follow-up (P⩽0.0001). Fourteen deaths occurred after a median follow-up of 37.5 months, eight of which were KS related. Suppression of HIV replication appears to be crucial to control KS. Non-PI-based regimens were equivalent to PI-based regimens as regards the clinical and virological outcome of antiretroviral-naive HIV-infected patients with KS

Tillering and forage accumulation in Marandu grass under different grazing intensities

Studies of plant responses to defoliation are important to develop pasture management strategies. The objective of this study was to evaluate the population density of basal, aerial and reproductive tillers, tiller appearance and mortality rates, forage accumulation and sward structure in Marandu grass pastures under different grazing intensities. The experimental period was from January to June 2006, divided in three seasons: summer, autumn and winter. The pastures were continuously grazed using variable stocking rates. The grazing intensities corresponded to 15, 30 and 45 cm of sward height. The experiment was arranged in a complete randomized block design with three treatments and two replicates. The sward heights were measured twice a week. The response variables were: forage accumulation, forage mass and its morphological components; and population densities of basal (TPDb), aerial (TPDa) and reproductive (TPDr) tillers. The highest TPDb (P > 0.05) was recorded for the shortest sward pasture, and the highest TPDr (P<0.05) for the tallest sward pasture. Swards showed a tiller size/density compensation mechanism and, consequently, the forage accumulation was similar (P > 0.05) among the grazing intensities. Pasture with a sward height of 35 cm had 94% of sun light interception. The highest variations in forage accumulation and sward structure were more influenced by seasonal differences than by grazing intensities. Pastures of Marandu grass showed large flexibility in grazing management, which allowed it to be maintained at sward heights between 15 and 35 cm