175 research outputs found
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Identifying HIV-1 host cell factors by genome-scale RNAi screening.
No full textAdvances in the application of RNA interference (RNAi) have facilitated the establishment of systematic cell-based loss-of-function screening platforms. Widespread implementation of this technology has enabled genome-wide genetic analysis of a diverse array of cellular phenotypes, including the identification of host cell factors involved in viral replication. Four recent studies employed whole-genome RNAi technologies to elucidate cellular genes important for the replication of HIV-1. While these four genome-scale screens shared a common objective, they differ in their scope and experimental design. In this review we explore alternative strategies for developing RNAi screens, and discuss potential pitfalls of the technology. Important technical considerations include the choice of silencing reagents, experimental systems, assay readout and analysis methods. We focus on experimental and computational parameters that can impact the outcome of high-throughput genetic screens, and provide guidelines for the development of reliable cell-based RNAi screens
Low dimensional CH3NH3PbBr3 cubes for persistent luminescence: Energy variation of electron excitation
No full textRetrovirology / HIV-1 protease cleaves the serine-threonine kinases RIPK1 and RIPK2
No full textBackground: HIV-1 protease (PR) is essential for viral infectivity as it cleaves Gag and Gag-Pol polyprotein precursors during viral maturation. Recent evidence suggests that cellular proteins can also be cleaved by PR, perhaps representing an important viral strategy to counter host defense mechanisms. Receptor-interacting protein kinase 1 (RIPK1) and RIPK2 belong to a family of serine/threonine kinases with conserved domain architecture and important functions in apoptosis, necrosis and innate immunity. Results: We found that RIPK1 and RIPK2 but not other members of the RIP kinase family are cleaved by HIV-1 PR. In RIPK1, we identified a putative PR cleavage site; a mutation at this site rendered RIPK1 resistant to PR cleavage. RIPK1 and RIPK2 were cleaved during HIV-1 infection of T cell lines or primary activated CD4+ T cells. Interfering with the viral life cycle at different stages by the addition of specific inhibitors against RT, integrase, or PR, completely prevented RIPK1 and RIPK2 cleavage. Cleavage of RIPK1 disrupted RIPK1/RIPK3 complex formation and RIPK1-mediated induction of NF-kB. Conclusions: These findings indicate that RIPK1 and RIPK2 are targets of HIV-1 PR activity during infection, and their inactivation may contribute to modulation of cell death and host defense pathways by HIV-1
Breaking the Silence: Regulation of HIV Transcription and Latency on the Road to a Cure
No full textAntiretroviral therapy (ART) has brought the HIV/AIDS epidemic under control, but a curative strategy for viral eradication is still needed. The cessation of ART results in rapid viral rebound from latently infected CD4+ T cells, showing that control of viral replication alone does not fully restore immune function, nor does it eradicate viral reservoirs. With a better understanding of factors and mechanisms that promote viral latency, current approaches are primarily focused on the permanent silencing of latently infected cells (“block and lock”) or reactivating HIV-1 gene expression in latently infected cells, in combination with immune restoration strategies to eliminate HIV infected cells from the host (“shock and kill”). In this review, we provide a summary of the current, most promising approaches for HIV-1 cure strategies, including an analysis of both latency-promoting agents (LPA) and latency-reversing agents (LRA) that have shown promise in vitro, ex vivo, and in human clinical trials to reduce the HIV-1 reservoir
Determination of the weakest branch in a radial distribution network using local voltage stability indicator at the proximity of the voltage collapse point
No full textStatus of all branches of distribution networks in chronological order using distributed generation at optimal position
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