purification-high-yield-extracellular-vesicle-preparations-away-from

Purification of High Yield Extracellular Vesicle Preparations Away from Virus

One of the major hurdles in the field of extracellular vesicle (EV) research today is the ability to achieve purified EV preparations in a viral infection ...

George Mason University

American Type Culture Collection (ATCC)

Zika virus (ZIKV) has emerged as a global health threat due to its neuro-teratogenic effect and wide range of transmission routes. Most recently, ZIKV infection has been linked with both autoimmune disorders in adults and neurodevelopmental disorders in newborns. Researchers are exploring potential cellular and molecular mechanisms underlying the neuro-teratogenicity and related consequences by using various  cell culture methods and  animal models. Though some of the putative viral entry receptors have been identified for ZIKV entry into the target cells, the exact mechanism of ZIKV entry or induced pathology are still not clear. Some of the important host cellular pathways including the toll-like receptor (TLR), autophagy, apoptosis and unfolded protein response (UPR) pathways are considered potential mechanism(s) for ZIKV induced neuroinflammation and for neurodevelopmental disorders. Since there is still a dire need for efficient treatment and vaccine to prevent ZIKV mediated disorders, a better understanding of the interaction between virus and host cellular pathways could pave the way for development of targeted therapeutic intervention. In this review, we are focusing on the recent advances and current knowledge regarding the interaction of ZIKV with abovementioned pathways so as to provide basic understanding to execute further research that could aid in the development of novel therapeutic strategy.

Complementary Mechanisms Potentially Involved in the Pathology of Zika Virus.

Autophagy, a highly conserved process, serves to maintain cellular homeostasis in response to an extensive variety of internal and external stimuli. The classic, or canonical, pathway of autophagy involves the coordinated degradation and recycling of intracellular components and pathogenic material. Proper regulation of autophagy is critical to maintain cellular health, as alterations in the autophagy pathway have been linked to the progression of a variety of physiological and pathological conditions in humans, namely in aging and in viral infection. In addition to its canonical role as a degradative pathway, a more unconventional and non-degradative role for autophagy has emerged as an area of increasing interest. This process, known as secretory autophagy, is gaining widespread attention as many viruses are believed to use this pathway as a means to release and spread viral particles. Moreover, secretory autophagy has been found to intersect with other intracellular pathways, such as the biogenesis and secretion of extracellular vesicles (EVs). Here, we provide a review of the current landscape surrounding both degradative autophagy and secretory autophagy in relation to both aging and viral infection. We discuss their key features, while describing their interplay with numerous different viruses (i.e. hepatitis B and C viruses, Epstein-Barr virus, SV40, herpesviruses, HIV, chikungunya virus, dengue virus, Zika virus, Ebola virus, HTLV, Rift Valley fever virus, poliovirus, and influenza A virus), and compare secretory autophagy to other pathways of extracellular vesicle release. Lastly, we highlight the need for, and emphasize the importance of, more thorough methods to study the underlying mechanisms of these pathways to better advance our understanding of disease progression.

Autophagy, EVs, and Infections: A Perfect Question for a Perfect Time.

Neurological diseases and disorders are leading causes of death and disability worldwide. Many of these pathologies are associated with high levels of neuroinflammation and irreparable tissue damage. As the global burden of these pathologies continues to rise there is a significant need for the development of novel therapeutics. Due to their multipotent properties, stem cells have broad applications for tissue repair; additionally, stem cells have been shown to possess both immunomodulatory and neuroprotective properties. It is now believed that paracrine factors, such as extracellular vesicles (EVs), play a critical role in the functionality associated with stem cells. The diverse biological cargo contained within EVs are proposed to mediate these effects and, to date, the reparative and regenerative effects of stem cell EVs have been demonstrated in a wide range of cell types. While a high potential for their therapeutic use exists, there is a gap of knowledge surrounding their characterization, mechanisms of action, and how they may regulate cells of the CNS. Here, we report the isolation, characterization, and functional assessment of EVs from two sources of human stem cells, mesenchymal stem cells and induced pluripotent stem cells. We demonstrate the ability of these EVs to enhance the processes of cellular migration and angiogenesis, which are critical for both normal cellular development as well as cellular repair. Furthermore, we investigate their reparative effects on damaged cells, specifically those with relevance to the central nervous system. Collectively, our data highlight the similarities and differences among these EV populations and support the view that stem cells EV can be used to repair or partially reverse cellular damage. Graphical Abstract Stem cell-derived Extracellular Vesicles (EVs) for repair of damaged cells. EVs isolated from human induced pluripotent stem cells and mesenchymal stem cells contribute to the partial reversal of phenotypes induced by different sources of cellular damage.

Article	Year
Complementary Mechanisms Potentially Involved in the Pathology of Zika Virus. Frontiers in immunology\| PubMed ID: 30374352	2018
Autophagy, EVs, and Infections: A Perfect Question for a Perfect Time. Frontiers in cellular and infection microbiology\| PubMed ID: 30406039	2018
Stem Cell Extracellular Vesicles and their Potential to Contribute to the Repair of Damaged CNS Cells. Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology\| PubMed ID: 31338754	2019

Heather Branscome

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