1,721,482 research outputs found
HIV-1 Tat, apoptosis and the mitochondria: a tubulin link?
No full textAbstract The Tat protein of HIV-1 is a powerful activator of viral gene expression. Besides this essential function at the HIV-1 promoter, the protein also exerts a remarkable number of other biological activities, among which the induction of cellular apoptosis. Two papers now published in Retrovirology provide possible molecular mechanisms for the pro-apoptotic effect of Tat, which involve the cell's microtubular network and the mitochondrial pathway of apoptosis.</p
Imaging HIV-1 nuclear pre-integration complexes.
No full textAdvancements in fluorescent microscopy techniques now permit investigation of HIV-1 biology exploiting tools alternative to conventional molecular biology. Here we describe a novel, fluorescence-based method to visualize HIV-1 viral particles within intact nuclei of infected cells. This method allows investigating the localization of pre-integration complexes within the nuclear compartment with respect to the nuclear envelope and the chromatin territories
Virus-mediated gene transfer to induce therapeutic angiogenesis: where do we stand?
No full textThe potential to induce therapeutic angiogenesis through gene transfer has engendered much excitement as a possible treatment for tissue ischemia. After 10 years of clinical experimentation, however, it now appears clear that several crucial issues are still to be resolved prior to achieving clinical success. These include the understanding of whether functional blood vessels might arise as a result of the delivery of a single angiogenic factor or require more complex cytokine combinations, the identification of the proper timing of therapeutic gene expression and, most notably, the development of more efficacious gene delivery tools. Viral vectors based on the adeno-associated virus (AAV) appear particularly suitable to address the last requirement, since they display a specific tropism for skeletal muscle cells and cardiomyocytes, and drive expression of the therapeutic genes in these cells for indefinite periods of time. In this review, I discuss the current applications of gene therapy for cardiovascular disorders, with particular attention to the possible improvements in the technologies involved in virus-mediated gene transfer
The HIV-1 Tat protein: a multifaceted target for novel therapeutic opportunities.
No full textTranscription of the integrated HIV-1 proviral genome is an essential step in the retrovirus life cycle and thus an appealing target for chemotherapeutic intervention to restrict retroviral replication. A fundamental role in this process is exerted by the viral protein Tat, a powerful transactivator of viral gene expression. This protein binds a structured RNA sequence at the 5'-ends of all nascent viral mRNAs and promotes transcription by mediating the recruitment to the viral promoter of cellular factors required for chromatin remodelling and transcriptional processivity. In addition to these transcriptional activities, Tat is released from the cells and enters neighbouring cells when present in the extracellular environment, a process that is possibly involved in HIV disease pathogenesis. Given its pleiotropic functions, the protein represents a highly appealing target for drug development. Here I will summarise the known molecular mechanisms by which Tat exerts its activities and review the currently available compounds that interfere with the process of transcriptional activation of the HIV-1 provirus
HIV Latency TORn Down
No full textCombination therapy for HIV infection is effective at controlling disease but fails to eradicate the virus because a persistent reservoir of cells harbors latent HIV DNA. In this issue of Cell Host & Microbe, Besnard
et al. (2016) show that the mTOR kinase is essential to reactivate HIV from latency
Gene Therapy to Induce Cellular Resistance to HIV-1 Infection: Lessons from Clinical Trials
No full textNon-redundant functions of the protein isoforms arising from alternative splicing of the VEGF-A pre-mRNA.
No full textThe different protein isoforms generated from the vascular endothelial growth factor-A (VEGF-A) gene, an essential regulator of blood vessel formation, differ in biochemical property and functional activity. Despite the relevance of VEGF-A for both normal and pathologic angiogenesis, our understanding of the molecular mechanisms governing alternative splicing of its pre-mRNA is still in its infancy
Gene transfer to promote cardiac regeneration
No full textThere is an impelling need to develop new therapeutic strategies for patients with myocardial infarction and heart failure. Leading from the large quantity of new information gathered over the last few years on the mechanisms controlling cardiomyocyte proliferation during embryonic and fetal life, it is now possible to devise innovative therapies based on cardiac gene transfer. Different protein-coding genes controlling cell cycle progression or cardiomyocyte specification and differentiation, along with microRNA mimics and inhibitors regulating pre-natal and early post-natal cell proliferation, are amenable to transformation in potential therapeutics for cardiac regeneration. These gene therapy approaches are conceptually revolutionary, since they are aimed at stimulating the intrinsic potential of differentiated cardiac cells to proliferate, rather than relying on the implantation of exogenously expanded cells to achieve tissue regeneration. For efficient and prolonged cardiac gene transfer, vectors based on the Adeno-Associated Virus stand as safe, efficient and reliable tools for cardiac gene therapy applications
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