The role of exosomal transport of viral agents in persistent HIV pathogenesis

Patters, Benjamin J.; Kumar, Santosh

doi:10.1186/s12977-018-0462-x

Cited by 35 publications

(26 citation statements)

References 144 publications

(167 reference statements)

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“…Since the human immunodeficiency virus 1 (HIV-1) was first reported in 1959, 74.9 million people have been infected (Whiteside and Wilson, 2018). Due to the high impact and importance of this disease, many efforts have been devoted to understand and characterize the mechanisms taking place in HIV infection and replication (von Schwedler et al, 2003;Pincetic and Leis, 2009;Meng and Lever, 2013;Patters and Kumar, 2018). For replication and virion production, HIV-1 Gag polyprotein play a key role (Bell and Lever, 2013).…”

Section: Introductionmentioning

confidence: 99%

An Alternative Perfusion Approach for the Intensification of Virus-Like Particle Production in HEK293 Cultures

Lavado‐García

Cervera

Gòdia

2020

Front. Bioeng. Biotechnol.

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Virus-like particles (VLPs) have gained interest over the last years as recombinant vaccine formats, as they generate a strong immune response and present storage and distribution advantages compared to conventional vaccines. Therefore, VLPs are being regarded as potential vaccine candidates for several diseases. One requirement for their further clinical testing is the development of scalable processes and production platforms for cell-based viral particles. In this work, the extended gene expression (EGE) method, which consists in consecutive media replacements combined with cell retransfections, was successfully optimized and transferred to a bioreactor operating in perfusion. A process optimization using design of experiments (DoE) was carried out to obtain optimal values for the time of retransfection, the cell specific perfusion rate (CSPR) and transfected DNA concentration, improving 86.7% the previously reported EGE protocol in HEK293. Moreover, it was successfully implemented at 1.5L bioreactor using an ATF as cell retention system achieving concentrations of 6.8•10 10 VLP/mL. VLP interaction with the ATF hollow fibers was studied via confocal microscopy, field emission scanning electron microscopy, and nanoparticle tracking analysis to design a bioprocess capable of separating unassembled Gag monomers and concentrate VLPs in one step.

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Section: Introductionmentioning

confidence: 99%

An Alternative Perfusion Approach for the Intensification of Virus-Like Particle Production in HEK293 Cultures

Lavado‐García

Cervera

Gòdia

2020

Front. Bioeng. Biotechnol.

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“…Currently, it is clear that exosomes also are vehicles for HIV particles in acquired immune deficiency syndrome (AIDS) infected persons, contributing to the overall pathogenic effect. Even though the effect is still persistent, it is now possible to target the mechanisms involved in sorting of the viral particles into exosomes [98]. Alternatively, other studies have shown that exosomes carrying HIV-1 protein Nef (exNef) as their cargo are prone to be engulfed by macrophages, causing the release of the exNef into the cellular space [99].…”

Section: Clinical Significance Of Exosomesmentioning

confidence: 99%

Inclusion Biogenesis, Methods of Isolation and Clinical Application of Human Cellular Exosomes

Tschuschke

Kocherova

Bryja

et al. 2020

JCM

139

101

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Exosomes are a heterogenous subpopulation of extracellular vesicles 30–150 nm in range and of endosome-derived origin. We explored the exosome formation through different systems, including the endosomal sorting complex required for transport (ESCRT) and ESCRT-independent system, looking at the mechanisms of release. Different isolation techniques and specificities of exosomes from different tissues and cells are also discussed. Despite more than 30 years of research that followed their definition and indicated their important role in cellular physiology, the exosome biology is still in its infancy with rapidly growing interest. The reasons for the rapid increase in interest with respect to exosome biology is because they provide means of intercellular communication and transmission of macromolecules between cells, with a potential role in the development of diseases. Moreover, they have been investigated as prognostic biomarkers, with a potential for further development as diagnostic tools for neurodegenerative diseases and cancer. The interest grows further with the fact that exosomes were reported as useful vectors for drugs.

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“…In recent studies, EVs, key players in cell-cell communication throughout the body, have emerged as biological components particularly important for their potential roles in physiological homeostasis, drug delivery systems, and therapeutics. In addition to these roles, EVs are implicated in many pathogenies, including cardiovascular disease [30], neurodegenerative disorders [31][32][33][34], traumatic brain injury [35,36], HIV [37,38], and a wide range of cancers [39][40][41][42][43]. More recently, studies indicate that EVs and their cargoes may play a significant role in modulating addiction across a variety of substances.…”

Section: Conclusion and Future Perspectivesmentioning

confidence: 99%

Role of Extracellular Vesicles in Substance Abuse and HIV-Related Neurological Pathologies

Odegaard

Chand

Wheeler

et al. 2020

IJMS

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Extracellular vesicles (EVs) are a broad, heterogeneous class of membranous lipid-bilayer vesicles that facilitate intercellular communication throughout the body. As important carriers of various types of cargo, including proteins, lipids, DNA fragments, and a variety of small noncoding RNAs, including miRNAs, mRNAs, and siRNAs, EVs may play an important role in the development of addiction and other neurological pathologies, particularly those related to HIV. In this review, we summarize the findings of EV studies in the context of methamphetamine (METH), cocaine, nicotine, opioid, and alcohol use disorders, highlighting important EV cargoes that may contribute to addiction. Additionally, as HIV and substance abuse are often comorbid, we discuss the potential role of EVs in the intersection of substance abuse and HIV. Taken together, the studies presented in this comprehensive review shed light on the potential role of EVs in the exacerbation of substance use and HIV. As a subject of growing interest, EVs may continue to provide information about mechanisms and pathogenesis in substance use disorders and CNS pathologies, perhaps allowing for exploration into potential therapeutic options.

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The role of exosomal transport of viral agents in persistent HIV pathogenesis

Cited by 35 publications

References 144 publications

An Alternative Perfusion Approach for the Intensification of Virus-Like Particle Production in HEK293 Cultures

An Alternative Perfusion Approach for the Intensification of Virus-Like Particle Production in HEK293 Cultures

Inclusion Biogenesis, Methods of Isolation and Clinical Application of Human Cellular Exosomes

Role of Extracellular Vesicles in Substance Abuse and HIV-Related Neurological Pathologies

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