Biochemical and Biologic Characterization of Exosomes and Microvesicles as Facilitators of HIV-1 Infection in Macrophages

Kadiu, Irena; Narayanasamy, Prabagaran; Dash, Prasanta K.; Zhang, Wei; Gendelman, Howard E.

doi:10.4049/jimmunol.1102244

Cited by 203 publications

(203 citation statements)

References 47 publications

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“…Several studies have reported that virus biogenesis and release converge with EV pathways, suggesting an evolutionary conserved system of virus-EV codependence (35)(36)(37)(38)(39). In fact, exosomes may be regarded as endogenous viruses as they have been shown to transfer various classes of nucleic acids (2)(3)(4)(5)(6).…”

Section: Discussionmentioning

confidence: 99%

Cancer cell exosomes depend on cell-surface heparan sulfate proteoglycans for their internalization and functional activity

Christianson

Svensson

Kuppevelt³

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

747

668

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Significance Exosome-mediated intercellular transfer of proteins and nucleic acids has attracted considerable attention as exosomes may promote the development of cancer and other pathological conditions; however, the mechanism of exosome uptake by target cells and how this may be inhibited remain as important questions. We provide evidence that heparan sulfate proteoglycans (HSPGs) function as receptors of cancer cell-derived exosomes. Importantly, our data indicate that the HSPG-dependent uptake route is highly relevant for the biological activity of exosomes, and thus a potential target for inhibition of exosome-mediated tumor development. Given that several viruses have previously been shown to enter cells through HSPGs, our data implicate HSPG as a convergence point during cellular uptake of endogenous vesicles and virus particles.

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Section: Discussionmentioning

confidence: 99%

Cancer cell exosomes depend on cell-surface heparan sulfate proteoglycans for their internalization and functional activity

Christianson

Svensson

Kuppevelt³

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

747

668

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“…In fact, this immune evasion strategy via secreted MPs has been previously described for other viruses. Microvesicles released from infected cells facilitate the spread of human immunodeficiency virus and herpes simplex virus to neighboring uninfected cells by transferring either viral constituents or the host's membrane proteins required for viral entry to other null cells, thereby increasing the number of susceptible cells (45)(46)(47).…”

Section: Discussionmentioning

confidence: 99%

Microparticles Provide a Novel Biomarker To Predict Severe Clinical Outcomes of Dengue Virus Infection

Punyadee

Mairiang

Thiemmeca

et al. 2015

J Virol

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Shedding of microparticles (MPs) is a consequence of apoptotic cell death and cellular activation. Low levels of circulating MPs in blood help maintain homeostasis, whereas increased MP generation is linked to many pathological conditions. Herein, we investigated the role of MPs in dengue virus (DENV) infection. Infection of various susceptible cells by DENV led to apoptotic death and MP release. These MPs harbored a viral envelope protein and a nonstructural protein 1 (NS1) on their surfaces. Ex vivo analysis of clinical specimens from patients with infections of different degrees of severity at multiple time points revealed that MPs generated from erythrocytes and platelets are two major MP populations in the circulation of DENV-infected patients. Elevated levels of red blood cell-derived MPs (RMPs) directly correlated with DENV disease severity, whereas a significant decrease in platelet-derived MPs was associated with a bleeding tendency. Removal by mononuclear cells of complement-opsonized NS1-anti-NS1 immune complexes bound to erythrocytes via complement receptor type 1 triggered MP shedding in vitro, a process that could explain the increased levels of RMPs in severe dengue. These findings point to the multiple roles of MPs in dengue pathogenesis. They offer a potential novel biomarker candidate capable of differentiating dengue fever from the more serious dengue hemorrhagic fever. IMPORTANCEDengue is the most important mosquito-transmitted viral disease in the world. No vaccines or specific treatments are available. Rapid diagnosis and immediate treatment are the keys to achieve a positive outcome. Dengue virus (DENV) infection, like some other medical conditions, changes the level and composition of microparticles (MPs), tiny bag-like structures which are normally present at low levels in the blood of healthy individuals. This study investigated how MPs in culture and patients' blood are changed in response to DENV infection. Infection of cells led to programmed cell death and MP release. In patients' blood, the majority of MPs originated from red blood cells and platelets. Decreased platelet-derived MPs were associated with a bleeding tendency, while increased levels of red blood cell-derived MPs (RMPs) correlated with more severe disease. Importantly, the level of RMPs during the early acute phase could serve as a biomarker to identify patients with potentially severe disease who require immediate care. E ach year, up to 390 million people are infected by dengue virus (DENV), the most significant mosquito-borne virus of the Flaviviridae family, posing serious socioeconomic and health burdens globally (1). Four serotypes of viruses (DENV serotype 1 [DENV-1], DENV-2, DENV-3, and DENV-4) are transmitted to humans by Aedes mosquitoes to establish both endemic and epidemic transmission cycles primarily in tropical and subtropical countries (1). Although the majority of DENV infections in humans are subclinical, a small fraction of infected individuals develops clinical symptoms ranging from a self-...

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“…Conversely, macrophages, which share the hematopoietic origin, func- tional phenotypes, and markers with microglia and are virtually undistinguishable from brain resident myeloid cells in the inflamed brain [24 -30], can be easily expanded in vitro and efficiently release MVs during pathological processes, such as viral infection [31] and cancer [32].…”

Section: Discussionmentioning

confidence: 99%

Activated macrophages release microvesicles containing polarized M1 or M2 mRNAs

Garzetti¹,

Menon²,

Finardi³

et al. 2013

Journal of Leukocyte Biology

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MVs are known vehicles of horizontal communication among cells, currently under scrutiny as powerful biomarkers in several pathological processes. The potential advantage of MVs relies on the assumption that their content reflects processes ongoing in pathologically relevant cell types. We have described that MVs of myeloid origin in the CSF are a marker of microglia/ macrophage activation. Myeloid cells have different activation types, resulting in diverse functional phenotypes. Knowledge on the activation type of myeloid cells during disease would be of paramount importance for the understanding of ongoing pathogenic processes. We show here that macrophages activated in vitro in different ways all release increased amounts of MVs compared with NS cells. Moreover, we show that macrophage-derived MVs contain a repertoire of mRNAs that is not the result of casual sampling from the parental cells, as it is characterized by distinct mRNA enrichments and species. Nevertheless, mRNA content of MVs clearly allows identification in vivo of the activated phenotype of the cell of origin, indicating carryover of functional macrophage traits. We propose that detection of mRNAs in myeloid MVs permits identification of myeloid cell activation type during disease, allowing for further stratification of pathological processes. J. Leukoc. Biol. 95: 817-825; 2014.

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Biochemical and Biologic Characterization of Exosomes and Microvesicles as Facilitators of HIV-1 Infection in Macrophages

Cited by 203 publications

References 47 publications

Cancer cell exosomes depend on cell-surface heparan sulfate proteoglycans for their internalization and functional activity

Cancer cell exosomes depend on cell-surface heparan sulfate proteoglycans for their internalization and functional activity

Microparticles Provide a Novel Biomarker To Predict Severe Clinical Outcomes of Dengue Virus Infection

Activated macrophages release microvesicles containing polarized M1 or M2 mRNAs

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