The Role of Small Extracellular Vesicles in Viral-Protozoan Symbiosis: Lessons From Trichomonasvirus in an Isogenic Host Parasite Model

Govender, Yashini; Chan, Tiffany; Yamamoto, Hidemi S.; Budnik, Bogdan; Fichorova, Raina N.

doi:10.3389/fcimb.2020.591172

Cited by 21 publications

(36 citation statements)

References 38 publications

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“…Our proteomics study has successfully identified TVV capsid proteins in sEVs released from T. vaginalis . Although Govender et al [ 25 ] could not identify any proteins of TVV origin in sEVs by LC-MS/MS, their experimental data supported the idea that viral endosymbiont may use sEVs as a vehicle for intercellular communications and deliver proteins to suppress host immune activation.…”

Section: Discussionmentioning

confidence: 99%

“…Mononuclear leukocytes increased their interleukin-6 (IL-6), IL-8, and tumor necrosis factor-α (TNF-α) output in response to sEVs from TVV-negative but not isogenic TVV-positive parasites. It is theoretically possible that sEVs may carry whole TVV virions or genomic dsRNA [ 25 ]. The TVV virions are at most 45 nm in diameter [ 40 ] and may fit into sEVs with a size of approximately 100 nm.…”

Section: Discussionmentioning

confidence: 99%

“…Thus, TVV-positive T. vaginalis isolates can express P270 in the cytoplasm and cell surface. Moreover, Govender et al [ 25 ] demonstrated that viral endosymbiosis altered the immunomodulatory properties of sEVs spreading from the site of infection to non-infected immune effector cells. More specifically, when human vaginal epithelial cells were incubated with T. vaginalis isolates with TVV-positive and TVV-negative, sEVs from TVV-negative but not TVV-positive parasites cultured alone caused NF-ĸB activation and an increase in IL-8 and RANTES expression, which provide innate immune defense at the gate to the upper reproductive tract [ 25 ].…”

Section: Introductionmentioning

confidence: 99%

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Identification of Endosymbiotic Virus in Small Extracellular Vesicles Derived from Trichomonas vaginalis

Ong

Cheng

et al. 2022

Genes

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Accumulated evidence suggests that the endosymbiotic Trichomonasvirus (TVV) may play a role in the pathogenesis and drug susceptibility of Trichomonas vaginalis. Several reports have shown that extracellular vesicles (EVs) released from TVV-positive (TVV+) trichomonads can modulate the immune response in human vaginal epithelial cells and animal models. These results prompted us to examine whether EVs released from TVV+ isolates contained TVV. We isolated small extracellular vesicles (sEVs) from six T. vaginalis isolates that were either TVV free (ATCC 50143), harbored a single (ATCC 30236, ATCC 30238, T1), two (ATCC PRA-98), or three TVV subspecies (ATCC 50148). The presence of TVV subspecies in the six isolates was observed using reverse transcription-polymerase chain reaction (RT-PCR). Transmission electron microscopy (TEM) confirmed the presence of cup-shaped sEVs with a size range from 30–150 nm. Trichomonas vaginalis tetraspanin (TvTSP1; TVAG_019180), the classical exosome marker, was identified in all the sEV preparations. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis showed that all the sEVs isolated from TVV+ isolates contain viral capsid proteins derived from the same TVV subspecies in that isolate as demonstrated by RT-PCR. To provide more comprehensive information on the TVV subspecies population in other T. vaginalis isolates, we investigated the distribution of TVV subspecies in twenty-four isolates by mining the New-Generation Sequencing (NGS) RNAseq datasets. Our results should be beneficial for future studies investigating the role of TVV on the pathogenicity of T. vaginalis and the possible transmission of virus subspecies among different isolates via sEVs.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Identification of Endosymbiotic Virus in Small Extracellular Vesicles Derived from Trichomonas vaginalis

Ong

Cheng

et al. 2022

Genes

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“…The presence of microorganisms as host symbionts is an important aim of the search for an explanation of the theory of infection; thus, it is an increasingly studied subject ( Hussa and Goodrich-Blair, 2013 ). Also, we intend to continue this research in order to clarify if microbiome represented by symbiosis predominantly between bacteria M. pneumoniae and B. burgdorferi with viruses induces release of small extracellular vesicles (sEVs) associated with abnormal cellular immune response, as described in the literature ( Christodoulides et al., 2018 ), and if these are present in the rejection episodes in morphomolecular studies of biopsies after CT ( Govender et al, 2020 ). These studies may support the concept that symbiosis with viruses may provide benefit to the main symbiont by exploiting sEVs as a vehicle for intercellular communications and modifying host immune response activation.…”

Section: Discussionmentioning

confidence: 99%

Distinct Microbial Communities in Dilated Cardiomyopathy Explanted Hearts Are Associated With Different Myocardial Rejection Outcomes

Pereira

Ikegami

Kawakami

et al. 2021

Front. Cell. Infect. Microbiol.

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BackgroundIdiopathic dilated cardiomyopathy (IDCM) myocardial inflammation may be associated with external triggering factors such as infectious agents. Here, we searched if moderate/severe heart transplantation rejection is related to the presence of myocardial inflammation in IDCM explanted hearts, associated with microbial communities.MethodReceptor myocardial samples from 18 explanted hearts were separated into groups according to post-transplant outcome: persistent moderate rejection (PMR; n = 6), moderate rejection (MR; n = 7) that regressed after pulse therapy, and no rejection (NR; n = 5)/light intensity rejection. Inflammation was quantified through immunohistochemistry (IHC), and infectious agents were evaluated by IHC, molecular biology, in situ hybridization technique, and transmission electron microscopy (TEM).ResultsNR presented lower numbers of macrophages, as well as B cells (p = 0.0001), and higher HLA class II expression (p ≤ 0.0001). PMR and MR showed higher levels of Mycoplasma pneumoniae (p = 0.003) and hepatitis B core (p = 0.0009) antigens. NR presented higher levels of parvovirus B19 (PVB19) and human herpes virus 6 (HHV6) and a positive correlation between Borrelia burgdorferi (Bb) and enterovirus genes. Molecular biology demonstrated the presence of M. pneumoniae, Bb, HHV6, and PVB19 genes in all studied groups. TEM revealed structures compatible with the cited microorganisms.ConclusionsThis initial study investigating on infectious agents and inflammation in the IDCM explanted hearts showed that the association between M. pneumoniae and hepatitis B core was associated with a worse outcome after HT, represented by MR and PMR, suggesting that different IDCM microbial communities may be contributing to post-transplant myocardial rejection.

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“…Of note, more than one TVV species can coexist in the same T. vaginalis cell ( Benchimol et al., 2002 ), and a high percentage of Trichomonasvirus in different protozoan isolates have been reported worldwide, ranging from 30% to 100% ( Fichorova et al., 2017 ), which may lead to the discrepancy of the findings. The implications of these co-infections so far are unclear, but evidence has shown that the TTV released from infected T. vaginalis cells induced inflammation upon treatment with metronidazole (MTZ) and may suppress host immune activation ( Fichorova et al., 2012 ; Govender et al., 2020 ). Each viral strain affects different aspects of the parasite.…”

Section: Prospects About Of Mucosa-associated Protozoa Infections Per...mentioning

confidence: 99%

An Overview of Mucosa-Associated Protozoa: Challenges in Chemotherapy and Future Perspectives

Santos

Rebello

2022

Front. Cell. Infect. Microbiol.

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Parasitic infections caused by protozoans that infect the mucosal surfaces are widely neglected worldwide. Collectively, Entamoeba histolytica, Giardia lamblia, Cryptosporidium spp. and Trichomonas vaginalis infect more than a billion people in the world, being a public health problem mainly in developing countries. However, the exact incidence and prevalence data depend on the population examined. These parasites ultimately cause pathologies that culminate in liver abscesses, malabsorption syndrome, vaginitis, and urethritis, respectively. Despite this, the antimicrobial agents currently used to treat these diseases are limited and often associated with adverse side effects and refractory cases due to the development of resistant parasites. The paucity of drug treatments, absence of vaccines and increasing problems of drug resistance are major concerns for their control and eradication. Herein, potential candidates are reviewed with the overall aim of determining the knowledge gaps and suggest future perspectives for research. This review focuses on this public health problem and focuses on the progress of drug repositioning as a potential strategy for the treatment of mucosal parasites.

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The Role of Small Extracellular Vesicles in Viral-Protozoan Symbiosis: Lessons From Trichomonasvirus in an Isogenic Host Parasite Model

Abstract: activities. These data support the concept that symbiosis with viruses may provide benefit to the protozoan parasite by exploiting sEVs as a vehicle for inter-cellular communications and modifying their protein cargo to suppress host immune activation.

Cited by 21 publications

References 38 publications

Identification of Endosymbiotic Virus in Small Extracellular Vesicles Derived from Trichomonas vaginalis

Identification of Endosymbiotic Virus in Small Extracellular Vesicles Derived from Trichomonas vaginalis

Distinct Microbial Communities in Dilated Cardiomyopathy Explanted Hearts Are Associated With Different Myocardial Rejection Outcomes

An Overview of Mucosa-Associated Protozoa: Challenges in Chemotherapy and Future Perspectives

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