Provirus activation plus CD59 blockage triggers antibody-dependent complement-mediated lysis of latently HIV-1-infected cells

Latently HIV-1-infected cells are recognized as the last barrier toward viral eradication and cure. To purge these cells, we combined a provirus stimulant with a blocker of human CD59, a key member of the regulators of complement activation, to trigger Ab-dependent complement-mediated lysis. Provirus stimulants including prostratin and histone deacetylase inhibitors such as romidepsin and suberoylanilide hydroxamic acid activated proviruses in the latently HIV-1-infected T cell line ACH-2 as virion production and viral protein expression on the cell surface were induced. Romidepsin was the most attractive provirus stimulant as it effectively activated proviruses at nanomolar concentrations that can be achieved clinically. Antiretroviral drugs including two protease inhibitors (atazanavir and darunavir) and an RT inhibitor (emtricitabine) did not affect the activity of provirus stimulants in the activation of proviruses. However, saquinavir (a protease inhibitor) markedly suppressed virus production, although it did not affect the percentage of cells expressing viral Env on the cell surface. Provirus-activated ACH-2 cells expressed HIV-1 Env that colocalized with CD59 in lipid rafts on the cell surface, facilitating direct interaction between them. Blockage of CD59 rendered provirus-activated ACH-2 cells and primary human CD4(+) T cells that were latently infected with HIV-1 sensitive to Ab-dependent complement-mediated lysis by anti-HIV-1 polyclonal Abs or plasma from HIV-1-infected patients. Therefore, a combination of provirus stimulants with regulators of complement activation blockers represents a novel approach to eliminate HIV-1

Effects of temperature, CO content, and reduction time on the selective reduction of a limonitic laterite ore

The production of nickel and cobalt from laterite ores has gained increasing attention as their demands continue to rise. This study evaluated the effects of temperature (700–1000 °C), CO content (10–70 vol%), and reduction time (10–90 min) on the selective reduction of a limonitic laterite ore and examined the mechanism of the selective reduction. SEM/EDS observation shows that the ore consists of goethite, hematite and small particles of clinochlore cemented by amorphous iron-rich silicate phase. Nickel and cobalt occur with goethite mineral in this ore. It was observed that fine grains of Fe-Ni-Co alloy dispersed within magnetite phase in reduced samples. XRD and XPS analyses show increased Fe2SiO4 generation with increasing reduction temperature, and elements nickel and cobalt were capatured in Fe2SiO4 according to SEM/EDS observation. Reduction at temperature above 850 °C resulted in a sharp increase in Fe2SiO4 generation and decrease in the specific surface area of the ore. The morphological and compositional observations indicate that CO content over 20 vol% promoted Fe formation from the laterite ore but hardly enhanced the formation of Ni and Co. The difference in equilibrium CO partial pressures for the formation of Fe, Ni, Co accounts for selective reduction. The current study suggests that selective reduction can be achieved by controlling reduction temperature and gas composition. Under the optimum condition of 850 °C, 20 vol% CO-80 vol% CO2 and 60 min, the degrees of metallisation of iron, nickel, and cobalt reduction were 17.5%, 87.3%, and 91.5%, respectively