Presence of Tat and transactivation response element in spinal fluid despite antiretroviral therapy

Cells continuously secrete a large number of microvesicles, macromolecular complexes, and small molecules into the extracellular space. Of the secreted microvesicles, the nanoparticles called exosomes are currently undergoing intense scrutiny. These are small vesicles (30-120 nm) containing nucleic acid and protein, perceived to be carriers of this cargo between diverse locations in the body. They are distinguished in their genesis by being budded into endosomes to form multivesicular bodies (MVBs) in the cytoplasm. The exosomes are released to extracellular fluids by fusion of these multivesicular bodies with the cell surface, resulting in secretion in bursts. Exosomes are secreted by all types of cells in culture, and also found in abundance in body fluids including blood, saliva, urine, and breast milk. In this review, we summarize strategies for exosome isolation, our understanding to date of exosome composition, functions, and pathways, and discuss their potential for diagnostic and therapeutic applications. Currently, the control of exosome formation, the makeup of the "cargo", biological pathways and resulting functions are incompletely understood. One of their most intriguing roles is intercellular communication--exosomes are thought to function as the messengers, delivering various effectors or signaling macromolecules between supposedly very specific cells. Both seasoned and newer investigators of nanovesicles have presented various viewpoints on what exosomes are, with some differences but a large common area. It would be useful to develop a codified definition of exosomes in both descriptive and practical terms. We hope this in turns leads to a consistent set of practices for their isolation, characterization and manipulation. Copyright © 2012 Elsevier B.V. All rights reserved.

Recent studies suggest both normal and cancerous cells secrete vesicles into the extracellular space. These extracellular vesicles (EVs) contain materials that mirror the genetic and proteomic content of the secreting cell. The identification of cancer-specific material in EVs isolated from the biofluids (e.g., serum, cerebrospinal fluid, urine) of cancer patients suggests EVs as an attractive platform for biomarker development. It is important to recognize that the EVs derived from clinical samples are likely highly heterogeneous in make-up and arose from diverse sets of biologic processes. This article aims to review the biologic processes that give rise to various types of EVs, including exosomes, microvesicles, retrovirus like particles, and apoptotic bodies. Clinical pertinence of these EVs to neuro-oncology will also be discussed.

The success of antiretroviral therapy has led some people to now ask whether the end of AIDS is possible. For patients who are motivated to take therapy and who have access to lifelong treatment, AIDS-related illnesses are no longer the primary threat, but a new set of HIV-associated complications have emerged, resulting in a novel chronic disease that for many will span several decades of life. Treatment does not fully restore immune health; as a result, several inflammation-associated or immunodeficiency complications such as cardiovascular disease and cancer are increasing in importance. Cumulative toxic effects from exposure to antiretroviral drugs for decades can cause clinically-relevant metabolic disturbances and end-organ damage. Concerns are growing that the multimorbidity associated with HIV disease could affect healthy ageing and overwhelm some health-care systems, particularly those in resource-limited regions that have yet to develop a chronic care model fully. In view of the problems inherent in the treatment and care for patients with a chronic disease that might persist for several decades, a global effort to identify a cure is now underway. Copyright © 2013 Elsevier Ltd. All rights reserved.