Exosomes Released from Rabies Virus-Infected Cells May be Involved in the Infection Process

Wang, Jingyu; Wu, Fan; Liu, Chuntian; Dai, Wenwen; Teng, Yawei; Su, Weiheng; Kong, Wei; Gao, Feng; Cai, Linjun; Hou, Ali; Jiang, Chunlai

doi:10.1007/s12250-019-00087-3

Cited by 25 publications

(16 citation statements)

References 36 publications

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“…The increase in vesicle marker intensity could be occurring through two ways: HCMV infection could increase the number of vesicles released from the cell, or infected cells may release vesicles with a higher enrichment of these molecules per vesicle. Viral infections were previously shown to increase the release of EVs from infected cells (17,38). To address this possibility, we analyzed the vesicle population by nanoparticle tracking analysis (NTA).…”

Section: Resultsmentioning

confidence: 99%

Human Cytomegalovirus Utilizes Extracellular Vesicles To Enhance Virus Spread

Streck

Zhao

Sundstrom

et al. 2020

J Virol

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Human cytomegalovirus (HCMV) manipulates cellular processes associated with secretory pathways within an infected cell to facilitate efficient viral replication. However, little is known about how HCMV infection alters the surrounding cellular environment to promote virus spread to uninfected cells. Extracellular vesicles (EVs) are key signaling molecules that are commonly altered in numerous disease states. Previous reports have shown that viruses commonly alter EVs, which can significantly impact infection. This study finds that HCMV modulates EV biogenesis machinery through upregulation of the endosomal sorting complex required for transport (ESCRT) proteins. This regulation appears to increase the activity of EV biogenesis, since HCMV-infected fibroblasts have increased vesicle release and altered vesicle size compared to EVs from uninfected cells. EVs generated through ESCRT-independent pathways are also beneficial to virus spread in fibroblasts, as treatment with the EV inhibitor GW4869 slowed the efficiency of HCMV spread. Importantly, the transfer of EVs purified from HCMV-infected cells enhanced virus spread. This suggests that HCMV modulates the EV pathway to transfer proviral signals to uninfected cells that prime the cellular environment for incoming infection and enhance the efficiency of virus spread. IMPORTANCE Human cytomegalovirus (HCMV) is a herpesvirus that leads to serious health consequences in neonatal or immunocompromised patients. Clinical management of infection in these at-risk groups remains a serious concern even with approved antiviral therapies available. It is necessary to increase our understanding of the cellular changes that occur during infection and their importance to virus spread. This may help to identify new targets during infection that will lead to the development of novel treatment strategies. Extracellular vesicles (EVs) represent an important method of intercellular communication in the human host. This study finds that HCMV manipulates this pathway to increase the efficiency of virus spread to uninfected cells. This finding defines a new layer of host manipulation induced by HCMV infection that leads to enhanced virus spread.

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Section: Resultsmentioning

confidence: 99%

Human Cytomegalovirus Utilizes Extracellular Vesicles To Enhance Virus Spread

Streck

Zhao

Sundstrom

et al. 2020

J Virol

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“…During infection, EVs can amplify inflammation and deflagrate antiviral responses (Urbanelli et al, 2019) and can also mediate communication between immune cells and other cell types (Isola and Chen, 2017). The involvement of EVs in viral infection and/or host interactions in disease has already been described for several viruses, such as rabies (Wang et al, 2019b), coronaviruses (Maeda et al, 1999;Kuate et al, 2007;Börger et al, 2020;Deffune et al, 2020;Hassanpour et al, 2020;Inal, 2020a;Inal, 2020b;Kumar et al, 2020;O'Driscoll, 2020;Tsuchiya et al, 2020;Urciuoli and Peruzzi, 2020), HCV (Bartosch et al, 2003;Timpe et al, 2008;Dreux et al, 2012;Bukong et al, 2014), HBV (Jia et al, 2017;, HIV (Princen et al, 2004;Khatua et al, 2009;Xu et al, 2009;Lenassi et al, 2010;Bernard et al, 2014;Raymond et al, 2016;Sampey et al, 2016;Kodidela et al, 2018;Haque et al, 2020;Ranjit et al, 2020), HPV (Honegger et al, 2015;Guenat et al, 2017;Sadri Nahand et al, 2019;Chiantore et al, 2020), HSV (Temme et al, 2010;Han et al, 2016;Deschamps and Kalamvoki, 2018) dengue (Martins et al, 2018;…”

Section: Evs In Immune Communication and Cytokine Responses During Inmentioning

confidence: 98%

Extracellular Vesicles in Viral Infections: Two Sides of the Same Coin?

Martins

Alves

2020

Front. Cell. Infect. Microbiol.

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Extracellular vesicles are small membrane structures containing proteins and nucleic acids that are gaining a lot of attention lately. They are produced by most cells and can be detected in several body fluids, having a huge potential in therapeutic and diagnostic approaches. EVs produced by infected cells usually have a molecular signature that is very distinct from healthy cells. For intracellular pathogens like viruses, EVs can have an even more complex function, since the viral biogenesis pathway can overlap with EV pathways in several ways, generating a continuum of particles, like naked virions, EVs containing infective viral genomes and quasi-enveloped viruses, besides the classical complete viral particles that are secreted to the extracellular space. Those particles can act in recipient cells in different ways. Besides being directly infective, they also can prime neighbor cells rendering them more susceptible to infection, block antiviral responses and deliver isolated viral molecules. On the other hand, they can trigger antiviral responses and cytokine secretion even in uninfected cells near the infection site, helping to fight the infection and protect other cells from the virus. This protective response can also backfire, when a massive inflammation facilitated by those EVs can be responsible for bad clinical outcomes. EVs can help or harm the antiviral response, and sometimes both mechanisms are observed in infections by the same virus. Since those pathways are intrinsically interlinked, understand the role of EVs during viral infections is crucial to comprehend viral mechanisms and respond better to emerging viral diseases.

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“…The latter induces T cell apoptosis in vitro, a key feature of HIV infection [170]. Other examples include the transport of viral genome and replication proteins through exosomes released by cells infected by Rabies, Zika and hepatitis C viruses [67,171,172], facilitating their spread.…”

Section: Exosomes In Infectious Diseasesmentioning

confidence: 99%

Exosomes: Potential Disease Biomarkers and New Therapeutic Targets

et al. 2021

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Exosomes are extracellular vesicles released by cells, both constitutively and after cell activation, and are present in different types of biological fluid. Exosomes are involved in the pathogenesis of diseases, such as cancer, neurodegenerative diseases, pregnancy disorders and cardiovascular diseases, and have emerged as potential non-invasive biomarkers for the detection, prognosis and therapeutics of a myriad of diseases. In this review, we describe recent advances related to the regulatory mechanisms of exosome biogenesis, release and molecular composition, as well as their role in health and disease, and their potential use as disease biomarkers and therapeutic targets. In addition, the advantages and disadvantages of their main isolation methods, characterization and cargo analysis, as well as the experimental methods used for exosome-mediated drug delivery, are discussed. Finally, we present potential perspectives for the use of exosomes in future clinical practice.

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Exosomes Released from Rabies Virus-Infected Cells May be Involved in the Infection Process

Cited by 25 publications

References 36 publications

Human Cytomegalovirus Utilizes Extracellular Vesicles To Enhance Virus Spread

Human Cytomegalovirus Utilizes Extracellular Vesicles To Enhance Virus Spread

Extracellular Vesicles in Viral Infections: Two Sides of the Same Coin?

Exosomes: Potential Disease Biomarkers and New Therapeutic Targets

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