Caveolae Restrict Tiger Frog Virus Release in HepG2 cells and Caveolae-Associated Proteins Incorporated into Virus Particles

Zheng, Yi-Wen; Lin, Yifan; Mi, Shu; Qin, Xiao-Wei; Weng, Shaoping; He, Jianguo; Guo, Chang-Jun

doi:10.1038/srep21663

Cited by 10 publications

(10 citation statements)

References 54 publications

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“…CAV2 is a protein component of caveolae structures. A recent study demonstrated that the caveolae and, therefore, its components could act as restriction factor for Tiger Frog Virus (TFV) release in late steps of viral cycle [ 86 ] in another hepatocyte cell line, HepG2. As OROV entry is mediated by clathrin-endocytosis [ 16 ], we speculate that caveolae could be a restriction site for viral budding/release; therefore down-regulation of a structural component could favors viral release.…”

Section: Discussionmentioning

confidence: 99%

MicroRNA and cellular targets profiling reveal miR-217 and miR-576-3p as proviral factors during Oropouche infection

et al. 2018

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Oropouche Virus is the etiological agent of an arbovirus febrile disease that affects thousands of people and is widespread throughout Central and South American countries. Although isolated in 1950’s, still there is scarce information regarding the virus biology and its prevalence is likely underestimated. In order to identify and elucidate interactions with host cells factors and increase the understanding about the Oropouche Virus biology, we performed microRNA (miRNA) and target genes screening in human hepatocarcinoma cell line HuH-7. Cellular miRNAs are short non-coding RNAs that regulates gene expression post-transcriptionally and play key roles in several steps of viral infections. The large scale RT-qPCR based screening found 13 differentially expressed miRNAs in Oropouche infected cells. Further validation confirmed that miR-217 and miR-576-3p were 5.5 fold up-regulated at early stages of virus infection (6 hours post-infection). Using bioinformatics and pathway enrichment analysis, we predicted the cellular targets genes for miR-217 and miR-576-3p. Differential expression analysis of RNA from 95 selected targets revealed genes involved in innate immunity modulation, viral release and neurological disorder outcomes. Further analysis revealed the gene of decapping protein 2 (DCP2), a previous known restriction factor for bunyaviruses transcription, as a miR-217 candidate target that is progressively down-regulated during Oropouche infection. Our analysis also showed that activators genes involved in innate immune response through IFN-β pathway, as STING (Stimulator of Interferon Genes) and TRAF3 (TNF-Receptor Associated Factor 3), were down-regulated as the infection progress. Inhibition of miR-217 or miR-576-3p restricts OROV replication, decreasing viral RNA (up to 8.3 fold) and virus titer (3 fold). Finally, we showed that virus escape IFN-β mediated immune response increasing the levels of cellular miR-576-3p resulting in a decreasing of its partners STING and TRAF3. We concluded stating that the present study, the first for a Peribunyaviridae member, gives insights in its prospective pathways that could help to understand virus biology, interactions with host cells and pathogenesis, suggesting that the virus escapes the antiviral cellular pathways increasing the expression of cognates miRNAs.

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Section: Discussionmentioning

confidence: 99%

MicroRNA and cellular targets profiling reveal miR-217 and miR-576-3p as proviral factors during Oropouche infection

et al. 2018

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“…Although the combined data suggest a function of caveolae in viral biogenesis, an association with caveolin-1 alone does not directly demonstrate the involvement of caveolae in virus morphogenesis. In addition, siRNA-mediated knockdown of caveolin-1 was shown to have no effect on RSV morphogenesis and infection in cultured cells ( Kipper et al, 2015 ), and there is some evidence that caveolin-1 might have an anti-viral role during virus infection ( Gabor et al, 2013 ; Bohm et al, 2014 ; He et al, 2016 ). Thus, the role of caveolin-1 and caveolae in virus-infected cells remains unclear.…”

Section: Introductionmentioning

confidence: 99%

Caveolae provide a specialized membrane environment for respiratory syncytial virus assembly

Ludwig

Nguyen

Leong

et al. 2017

Journal of Cell Science

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Respiratory syncytial virus (RSV) is an enveloped virus that assembles into filamentous virus particles on the surface of infected cells. Morphogenesis of RSV is dependent upon cholesterol-rich (lipid raft) membrane microdomains, but the specific role of individual raft molecules in RSV assembly is not well defined. Here, we show that RSV morphogenesis occurs within caveolar membranes and that both caveolin-1 and cavin-1 (also known as PTRF), the two major structural and functional components of caveolae, are actively recruited to and incorporated into the RSV envelope. The recruitment of caveolae occurred just prior to the initiation of RSV filament assembly, and was dependent upon an intact actin network as well as a direct physical interaction between caveolin-1 and the viral G protein. Moreover, cavin-1 protein levels were significantly increased in RSV-infected cells, leading to a virus-induced change in the stoichiometry and biophysical properties of the caveolar coat complex. Our data indicate that RSV exploits caveolae for its assembly, and we propose that the incorporation of caveolae into the virus contributes to defining the biological properties of the RSV envelope.

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“…For this work, we set out to test whether PTRT might have some endocrine/paracrine influence beyond its effect as endogenous factor. Some studies have already reported the presence of extracellular PTRF in viral capsids [9] and in bladder cancer exosomas [24].Yet, this is the first report showing that PTRF circulates in the blood of individuals free of cancer or any viral disease. Moreover, we also proved that PTRF associated with exosomes.…”

Section: Discussionmentioning

confidence: 72%

PTRF acts as an adipokine contributing to adipocyte dysfunctionality and ectopic lipid deposition

et al. 2018

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Adipose tissue (AT) expands under obesogenic conditions. Yet, when the growth exceeds a certain limit, AT becomes dysfunctional and surplus lipids start depositing ectopically. Polymerase I and transcription release factor (PTRF) has been proposed as a mechanism leading to a dysfunctional AT by decreasing the adipogenic potential of human adipocyte precursors. However, whether or not PTRF can be secreted by the adipocytes into the bloodstream is not yet known. For this work, PTRF presence was investigated in plasma. We also produced a recombinant PTRF (rPTRF) and examined its impact on the functional interactions between the adipocyte and the hepatocyte in vitro. We demonstrated that PTRF can be found in human plasma, and is at least in part, carried by exosomes. In vitro treatment with rPTRF increased the hypertrophy and senescence of 3T3-L1 adipocytes. In turn, those rPTRF-treated adipocytes increased lipid accumulation in hepatocytes. Lastly, we found a positive correlation between circulating PTRF and the concentration of PTRF in the visceral fat depot. All these findings point toward the presence of an enlarged and dysfunctional visceral adipose tissue which secretes PTRF. This circulating PTRF behaves as an adipokine and may partially contribute to the well-known detrimental effects of visceral fat accumulation.

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Caveolae Restrict Tiger Frog Virus Release in HepG2 cells and Caveolae-Associated Proteins Incorporated into Virus Particles

Cited by 10 publications

References 54 publications

MicroRNA and cellular targets profiling reveal miR-217 and miR-576-3p as proviral factors during Oropouche infection

MicroRNA and cellular targets profiling reveal miR-217 and miR-576-3p as proviral factors during Oropouche infection

Caveolae provide a specialized membrane environment for respiratory syncytial virus assembly

PTRF acts as an adipokine contributing to adipocyte dysfunctionality and ectopic lipid deposition

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