Exosomes Derived from HIV-1 Infected DCs Mediate Viral trans-Infection via Fibronectin and Galectin-3

Kulkarni, Rutuja; Prasad, Anil

doi:10.1038/s41598-017-14817-8

Cited by 73 publications

(71 citation statements)

References 70 publications

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“…Other non-enveloped viruses, including picornaviruses and noroviruses have recently been shown to take advantage of extracellular vesicles to promote their transmission [36][37][38][39][40][41][42]. This mode of infection has been shown to be more efficient than infection by individual viral particles due to the increased multiplicity of infection of a vesicle containing many virions vs single virions in isolation [42].…”

Section: Discussionmentioning

confidence: 99%

JC Virus infected choroid plexus epithelial cells produce extracellular vesicles that infect glial cells independently of the virus attachment receptor

et al. 2020

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The human polyomavirus, JCPyV, is the causative agent of progressive multifocal leukoencephalopathy (PML) in immunosuppressed and immunomodulated patients. Initial infection with JCPyV is common and the virus establishes a long-term persistent infection in the urogenital system of 50-70% of the human population worldwide. A major gap in the field is that we do not know how the virus traffics from the periphery to the brain to cause disease. Our recent discovery that human choroid plexus epithelial cells are fully susceptible to virus infection together with reports of JCPyV infection of choroid plexus in vivo has led us to hypothesize that the choroid plexus plays a fundamental role in this process. The choroid plexus is known to relay information between the blood and the brain by the release of extracellular vesicles. This is particularly important because human macroglia (oligodendrocytes and astrocytes), the major targets of virus infection in the central nervous system (CNS), do not express the known attachment receptors for the virus and do not bind virus in human tissue sections. In this report we show that JCPyV infected choroid plexus epithelial cells produce extracellular vesicles that contain JCPyV and readily transmit the infection to human glial cells. Transmission of the virus by extracellular vesicles is independent of the known virus attachment receptors and is not neutralized by antisera directed at the virus. We also show that extracellular vesicles containing virus are taken into target glial cells by both clathrin dependent endocytosis and macropinocytosis. Our data support the hypothesis that the choroid plexus plays a fundamental role in the dissemination of virus to brain parenchyma.

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Section: Discussionmentioning

confidence: 99%

JC Virus infected choroid plexus epithelial cells produce extracellular vesicles that infect glial cells independently of the virus attachment receptor

et al. 2020

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“…). In addition to the studies discussed here, ECM immunological research, which is expanding into the areas of prion disease, virus transmission, exosomes in viral pathogenesis and vaccine development, shows the breadth and complexity of ECM activity and regulation in infection.…”

Section: Concluding Remarks and Future Perspectivesmentioning

confidence: 90%

A complex interplay between the extracellular matrix and the innate immune response to microbial pathogens

2018

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The role of the host extracellular matrix (ECM) in infection tends to be neglected. However, the complex interactions between invading pathogens, host tissues and immune cells occur in the context of the ECM. On the pathogen side, a variety of surface and secreted molecules, including microbial surface components recognizing adhesive matrix molecules and tissue-degrading enzymes, are employed that interact with different ECM proteins to effectively establish an infection at specific sites. Microbial pathogens can also hijack or misuse host proteolytic systems to modify the ECM, evade immune responses or process biologically active molecules such as cell surface receptors and cytokines that direct cell behaviour and immune defence. On the host side, the ECM composition and three-dimensional ultrastructure undergo significant modifications, which have a profound impact on the specific signals that the ECM conveys to immune cells at the forefront of infection. Unexpectedly, activated immune cells participate in the remodelling of the local ECM by synthesizing ECM glycoproteins, proteoglycans and collagen molecules. The close interplay between the ECM and the innate immune response to microbial pathogens ultimately affects the outcome of infection. This review explores and discusses recent data that implicate an active role for the ECM in the immune response to infection, encompassing antimicrobial activities, microbial recognition, macrophage activation, phagocytosis, leucocyte population balance, and transcriptional and post-transcriptional regulation of inflammatory networks, and may foster novel antimicrobial approaches.

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“…Contrariwise, exosomes can be pernicious biostructures when hijacked by different infective agents and consequently directed to spread the infection. This manipulative mechanism has been reported for HIV [34], EBV [35], HCV [36], as well as bacterial pathogens, specifically Mycobacterium tuberculosis [28] [37]. Recently, a similar mechanism has been uncovered for exosomal-mediated transmission of flavivirus RNAs and proteins to humans from arthropods such as the Ixodes scapularis 7 ticks [38].…”

mentioning

confidence: 60%

Exosomes: Biological Couriers with Transformative Messages

Yousef¹,

Abdelnaser²

2019

J. Biomed

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Exosomes are nanovesicles produced by almost all cell types to the extracellular environment. These structures, initially mistaken for "cellular dust", are key effectors of cell-cell communication and play major roles in maintaining normal physiological function and homeostatic balance as well as relaying pathology. Given their non-immunogenicity, their native membrane composition combined with the wealth of contained bioinfomative cargoes and coupled to their innate ability to cross multiple biological barriers, these tiny sacs have merited a great deal of interest in recent years and are slowly edging their way to the surface. Accruing evidence corroborating the far-reaching potential of exosomes is ever growing and easily demonstrable. Nonetheless, progress with translation of the reported outcomes to clinical settings and recognition of these tools as a multi-application platform remains much too inadequate for the outstanding potential of these biological messengers and the entailed shift in theragnostic paradigms. The purpose of this review is to recapitulate on the most recent advances in exosome research and accentuate their momentous promise as game changers in disease diagnostics and therapeutics. Finally, market transition and commercialization efforts are highlighted with a brief commentary on the status quo. Syndecans/syntenin system: Syndecans are membrane-associated proteoglycans, whereas syntenin is a syndecan-interacting protein. Syntenin contains a PDZ domain, which constitutes the site of interaction with syndecan. The syndecan/syntenin system has been proven to play a key role in exosomal biogenesis [98]. 4Cortactin: a protein involved in cytoskeletal modification.

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Exosomes Derived from HIV-1 Infected DCs Mediate Viral trans-Infection via Fibronectin and Galectin-3

Cited by 73 publications

References 70 publications

JC Virus infected choroid plexus epithelial cells produce extracellular vesicles that infect glial cells independently of the virus attachment receptor

JC Virus infected choroid plexus epithelial cells produce extracellular vesicles that infect glial cells independently of the virus attachment receptor

A complex interplay between the extracellular matrix and the innate immune response to microbial pathogens

Exosomes: Biological Couriers with Transformative Messages

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