scholarly journals Human Cytomegalovirus Infection Changes the Pattern of Surface Markers of Small Extracellular Vesicles Isolated From First Trimester Placental Long-Term Histocultures

Author(s):  
Mathilde Bergamelli ◽  
Hélène Martin ◽  
Mélinda Bénard ◽  
Jérôme Ausseil ◽  
Jean-Michel Mansuy ◽  
...  

Extracellular vesicles (EVs) have increasingly been recognized as key players in a wide variety of physiological and pathological contexts, including during pregnancy. Notably, EVs appear both as possible biomarkers and as mediators involved in the communication of the placenta with the maternal and fetal sides. A better understanding of the physiological and pathological roles of EVs strongly depends on the development of adequate and reliable study models, specifically at the beginning of pregnancy where many adverse pregnancy outcomes have their origin. In this study, we describe the isolation of small EVs from a histoculture model of first trimester placental explants in normal conditions as well as upon infection by human cytomegalovirus. Using bead-based multiplex cytometry and electron microscopy combined with biochemical approaches, we characterized these small EVs and defined their associated markers and ultrastructure. We observed that infection led to changes in the expression level of several surface markers, without affecting the secretion and integrity of small EVs. Our findings lay the foundation for studying the functional role of EVs during early pregnancy, along with the identification of new predictive biomarkers for the severity and outcome of this congenital infection, which are still sorely lacking.

2020 ◽  
Author(s):  
Mathilde Bergamelli ◽  
Hélène Martin ◽  
Mélinda Bénard ◽  
Jérôme Ausseil ◽  
Jean-Michel Mansuy ◽  
...  

ABSTRACTCurrently, research on the use of non-invasive biomarkers as diagnosis and prognosis tools during pathological pregnancies is in full development. Among these, placenta-derived small extracellular vesicles (sEVs) are considered as serious candidates, since their composition is modified during many pregnancy pathologies. Moreover, sEVs are found in maternal serum and can thus be easily purified from a simple blood sample. In this study, we describe the isolation of sEVs from a histoculture model of first trimester placental explants. Using bead-based multiplex cytometry and electron microscopy combined with biochemical approaches, we characterized these sEVs and defined their associated markers and ultrastructure. We next examined the consequences of infection by human cytomegalovirus on sEVs secretion and characteristics. We observed that infection led to increased levels of expression of several surface markers, without any impact on the secretion and integrity of sEVs. Our findings open the prospect for the identification of new predictive biomarkers for the severity and outcome of this congenital infection early during pregnancy, which are still sorely lacking.


Cells ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 767
Author(s):  
Courtney Davis ◽  
Sean I. Savitz ◽  
Nikunj Satani

Ischemic stroke is a debilitating disease and one of the leading causes of long-term disability. During the early phase after ischemic stroke, the blood-brain barrier (BBB) exhibits increased permeability and disruption, leading to an influx of immune cells and inflammatory molecules that exacerbate the damage to the brain tissue. Mesenchymal stem cells have been investigated as a promising therapy to improve the recovery after ischemic stroke. The therapeutic effects imparted by MSCs are mostly paracrine. Recently, the role of extracellular vesicles released by these MSCs have been studied as possible carriers of information to the brain. This review focuses on the potential of MSC derived EVs to repair the components of the neurovascular unit (NVU) controlling the BBB, in order to promote overall recovery from stroke. Here, we review the techniques for increasing the effectiveness of MSC-based therapeutics, such as improved homing capabilities, bioengineering protein expression, modified culture conditions, and customizing the contents of EVs. Combining multiple techniques targeting NVU repair may provide the basis for improved future stroke treatment paradigms.


2021 ◽  
Author(s):  
Sara B. York ◽  
Li Sun ◽  
Allaura S. Cone ◽  
Leanne C. Duke ◽  
Mujeeb R. Cheerathodi ◽  
...  

ABSTRACTExtracellular vesicles (EVs) are membrane-encapsulated structures released by cells which carry signaling factors, proteins and microRNAs that mediate intercellular communication. Accumulating evidence supports an important role of EVs in the progression of neurological conditions and both the spread and pathogenesis of infectious diseases. It has recently been demonstrated that EVs from Hepatitis C virus (HCV) infected individuals and cells contained replicative-competent viral RNA that was capable of infecting hepatocytes. Being a member of the same viral family, it is likely the Zika virus also hijacks EV pathways to package viral components and secrete vesicles that are infectious and potentially less immunogenic. As EVs have been shown to cross blood-brain and placental barriers, it is possible that Zika virus could usurp normal EV biology to gain access to the brain or developing fetus. Here, we demonstrate that Zika virus infected cells secrete distinct EV sub-populations with specific viral protein profiles and infectious genomes. Zika virus infection resulted in the enhanced production of EVs with varying sizes and density compared to those released from non-infected cells. We also show that the EV enriched tetraspanin CD63 regulates the release of EVs, and Zika viral genomes and capsids following infection. Overall, these findings provide evidence for an alternative means of Zika virus transmission and demonstrate the role of EV biogenesis and trafficking proteins in the modulation of Zika infection.ImportanceZika virus is a re-emerging infectious disease that spread rapidly across the Caribbean and South America. Infection of pregnant women during the first trimester has been linked to microcephaly, a neurological condition where babies are born with smaller heads due to abnormal brain development. Babies born with microcephaly can develop convulsions and suffer disabilities as they age. Despite the significance of Zika virus, little is known about how the virus infects the fetus or causes disease. Extracellular vesicles (EVs) are membrane-encapsulated structures released by cells that are present in all biological fluids. EVs carry signaling factors, proteins and microRNAs that mediate intercellular communication. EVs have been shown to be a means by which some viruses can alter cellular environments and cross previously unpassable cellular barriers. Thus gaining a greater understanding of how Zika affects EV cargo may aid in the development of better diagnostics, targeted therapeutics and prophylactic treatments.


2020 ◽  
Vol 8 (7) ◽  
pp. 1087
Author(s):  
Manuela Donalisio ◽  
Simona Cirrincione ◽  
Massimo Rittà ◽  
Cristina Lamberti ◽  
Andrea Civra ◽  
...  

Breast milk is a complex biofluid that nourishes infants, supports their growth and protects them from diseases. However, at the same time, breastfeeding is a transmission route for human cytomegalovirus (HCMV), with preterm infants being at a great risk of congenital disease. The discrepancy between high HCMV transmission rates and the few reported cases of infants with severe clinical illness is likely due to the protective effect of breast milk. The aim of this study was to investigate the anti-HCMV activity of human preterm colostrum and clarify the role of colostrum-derived extracellular vesicles (EVs). Preterm colostrum samples were collected and the EVs were purified and characterized. The in vitro anti-HCMV activity of both colostrum and EVs was tested against HCMV, and the viral replication step inhibited by colostrum-purified EVs was examined. We investigated the putative role EV surface proteins play in impairing HCMV infection using shaving experiments and proteomic analysis. The obtained results confirmed the antiviral action of colostrum against HCMV and demonstrated a remarkable antiviral activity of colostrum-derived EVs. Furthermore, we demonstrated that EVs impair the attachment of HCMV to cells, with EV surface proteins playing a role in mediating this action. These findings contribute to clarifying the mechanisms that underlie the protective role of human colostrum against HCMV infection.


Cancers ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 3696
Author(s):  
Kevin Ho Wai Yim ◽  
Ala’a Al Hrout ◽  
Simone Borgoni ◽  
Richard Chahwan

Extracellular vesicles (EVs) are emerging as potent and intricate intercellular communication networks. From their first discovery almost forty years ago, several studies have bolstered our understanding of these nano-vesicular structures. EV subpopulations are now characterized by differences in size, surface markers, cargo, and biological effects. Studies have highlighted the importance of EVs in biology and intercellular communication, particularly during immune and tumor interactions. These responses can be equally mediated at the proteomic and epigenomic levels through surface markers or nucleic acid cargo signaling, respectively. Following the exponential growth of EV studies in recent years, we herein synthesize new aspects of the emerging immune–tumor EV-based intercellular communications. We also discuss the potential role of EVs in fundamental immunological processes under physiological conditions, viral infections, and tumorigenic conditions. Finally, we provide insights on the future prospects of immune–tumor EVs and suggest potential avenues for the use of EVs in diagnostics and therapeutics.


2021 ◽  
Vol 12 ◽  
Author(s):  
Yao Yao ◽  
Xiaoyu Cai ◽  
Yiqing Ye ◽  
Fengmei Wang ◽  
Fengying Chen ◽  
...  

From early life to adulthood, the microbiota play a crucial role in the health of the infant. The microbiota in early life are not only a key regulator of infant health but also associated with long-term health. Pregnancy to early life is the golden time for the establishment of the infant microbiota, which is affected by both environmental and genetic factors. Recently, there is an explosion of the studies on the role of microbiota in human diseases, but the application to disease or health is relatively limited because many aspects of human microbiota remain controversial, especially about the infant microbiota. Therefore, a critical and conclusive review is necessary to understand fully the relationship between the microbiota and the health of infant. In this article, we introduce in detail the role of microbiota in the infant from pregnancy to early life to long-term health. The main contents of this article include the relationship between the maternal microbiota and adverse pregnancy outcomes, the establishment of the neonatal microbiota during perinatal period and early life, the composition of the infant gut microbiota, the prediction of the microbiota for long-term health, and the future study directions of microbiota.


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