Virus-like vesicles of Kaposi’s Sarcoma-Associated Herpesvirus activate lytic replication through triggering differentiation signaling (microRNA)
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PROVIDER: PRJNA356917 | ENA |
REPOSITORIES: ENA
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Project description:Virus-like vesicles of Kaposi’s Sarcoma-Associated Herpesvirus activate lytic replication through triggering differentiation signaling
| PRJNA356883 | ENA
Project description:Virus-like vesicles of Kaposi’s Sarcoma-Associated Herpesvirus activate lytic replication through triggering differentiation signaling (mRNA)
| PRJNA356918 | ENA
Project description:Virus-like vesicles (VLVs) are membrane derived cellular vesicles that resemble native envelope viruses in organization and conformation, but lack viral capsid and/or genome. During productive virus infection, both infectious virions and non-infectious VLVs are produced and released into the extracellular space. VLVs have been shown to play a role in intercellular communication and in facilitating virus infection. The study of VLVs in the context of gammaherpesvirus infection has been largely restricted due to the technical difficulty of separating VLVs and virions. Here we report a strategy for using a KSHV mutant deficient in capsid assembly to isolate VLVs during infection. Using Mass Spectrometry analysis, we identified that VLVs contain viral glycoproteins required for cellular entry, and tegument proteins involved in regulating lytic replication. Functional analysis showed that VLVs could activate the RTA promoter, the lytic switch for KSHV, and further induce KSHV lytic gene expression from latency. We used RNA sequencing to do a genome-wide analysis of cellular responses triggered by VLVs, and revealed that PRDM1, a master regulator in cell differentiation, was up-regulated. Our data shows that VLVs play an important role in promoting KSHV lytic replication by inducing PRDM1 expression which activates the RTA promoter. Our study significantly extends our current understanding of VLVs.
2017-05-03 | GSE91385 | GEO
Project description:Virus-like vesicles (VLVs) are membrane derived cellular vesicles that resemble native envelope viruses in organization and conformation, but lack viral capsid and/or genome. During productive virus infection, both infectious virions and non-infectious VLVs are produced and released into the extracellular space. VLVs have been shown to play a role in intercellular communication and in facilitating virus infection. The study of VLVs in the context of gammaherpesvirus infection has been largely restricted due to the technical difficulty of separating VLVs and virions. Here we report a strategy for using a KSHV mutant deficient in capsid assembly to isolate VLVs during infection. Using Mass Spectrometry analysis, we identified that VLVs contain viral glycoproteins required for cellular entry, and tegument proteins involved in regulating lytic replication. Functional analysis showed that VLVs could activate the RTA promoter, the lytic switch for KSHV, and further induce KSHV lytic gene expression from latency. We used RNA sequencing to do a genome-wide analysis of cellular responses triggered by VLVs, and revealed that PRDM1, a master regulator in cell differentiation, was up-regulated. Our data shows that VLVs play an important role in promoting KSHV lytic replication by inducing PRDM1 expression which activates the RTA promoter. Our study significantly extends our current understanding of VLVs.
2017-05-03 | GSE91384 | GEO
Project description:Historically, ribosomes have been viewed as unchanged homogeneous macromolecular machines with no intrinsic regulatory capacity for mRNA translation. However, an emerging concept is that heterogeneity of ribosomal composition exists, which can exert a regulatory function or specificity in translational control. This is supported by recent discoveries identifying compositionally distinct ‘specialised ribosomes’ that actively regulate mRNA translation. Viruses lack their own translational machinery and impose a high translational demand on the host cell during replication. Here we explore the possibility that Kaposi’s sarcoma-associated herpesvirus (KSHV) can manipulate host ribosome biogenesis during infection to produce specialised ribosomes which preferentially translate viral transcripts. Quantitative proteomic analysis has identified changes in the stoichiometry and composition of precursor ribosomal complexes during the switch from latent to lytic KSHV replication. Intriguingly, we demonstrate the enhanced association of ribosomal biogenesis factors BUD23 and NOC4L, and a previously uncharacterised KSHV lytic protein, ORF11, with small ribosomal subunit precursor complexes during lytic KSHV infection. Notably, BUD23 depletion resulted in significantly reduced viral gene expression and progression through the lytic cascade, culminating in a dramatic reduction of infectious virion production. Importantly, ribosome profiling demonstrated that BUD23 is essential for the reduced association of ribosomes with KSHV uORFs in late lytic genes, required for the efficient translation of the main open reading frame. Together our results provide new mechanistic insights into KSHV-mediated manipulation of cellular ribosome composition inducing a population of specialised ribosomes to facilitate efficient translation of viral mRNAs.
2022-12-21 | PXD032318 | Pride
Project description:Historically, ribosomes have been viewed as unchanged homogeneous macromolecular machines with no intrinsic regulatory capacity for mRNA translation. However, an emerging concept is that heterogeneity of ribosomal composition exists, which can exert a regulatory function or specificity in translational control. This is supported by recent discoveries identifying compositionally distinct ‘specialised ribosomes’ that actively regulate mRNA translation. Viruses lack their own translational machinery and impose a high translational demand on the host cell during replication. Here we explore the possibility that Kaposi’s sarcoma-associated herpesvirus (KSHV) can manipulate host ribosome biogenesis during infection to produce specialised ribosomes which preferentially translate viral transcripts. Quantitative proteomic analysis has identified changes in the stoichiometry and composition of precursor ribosomal complexes during the switch from latent to lytic KSHV replication. Intriguingly, we demonstrate the enhanced association of ribosomal biogenesis factors BUD23 and NOC4L, and a previously uncharacterised KSHV lytic protein, ORF11, with small ribosomal subunit precursor complexes during lytic KSHV infection. Notably, BUD23 depletion resulted in significantly reduced viral gene expression and progression through the lytic cascade, culminating in a dramatic reduction of infectious virion production. Importantly, ribosome profiling demonstrated that BUD23 is essential for the reduced association of ribosomes with KSHV uORFs in late lytic genes, required for the efficient translation of the main open reading frame. Together our results provide new mechanistic insights into KSHV-mediated manipulation of cellular ribosome composition inducing a population of specialised ribosomes to facilitate efficient translation of viral mRNAs.
2022-12-21 | PXD032367 | Pride
Project description:ChIP-sequencing reads from Oncogenic Herpesvirus utilizes stress-induced cell cycle checkpoints for efficient lytic replication, accepted to PLOS Pathogens
2016-06-01 | E-MTAB-4356 | biostudies-arrayexpress
Project description:This SuperSeries is composed of the SubSeries listed below.
2017-05-03 | GSE91386 | GEO
Project description:Epstein-Barr virus (EBV) Rta is a latent-lytic molecular switch evolutionarily conserved in all gamma-herpesviruses. In previous studies, doxycycline-inducible Rta was shown to potently produce an irreversible G1 arrest followed by cellular senescence in 293 cells. Here, we demonstrate that in this system the inducible Rta not only reactivates resident genome of EBV but also that of Kaposi’s sarcoma-associated herpesvirus (KSHV), to similar efficiency. However, Rta-induced senescence program was terminated by the robust viral lytic cycle replication that eventually caused cell death. Furthermore, prior to the abrupt expression of immediate-early protein (EBV BZLF1 or KSHV RTA), Rta simultaneously down-regulates cell cycle activators (c-Myc, CDK6, CCND2) and up-regulates senescence-related genes (p21, 14-3-3s). Since Rta is a viral immediate-early transcriptional activator, it is envisioned that during the initial stage of viral reactivation, Rta may engage to modulate the host transcriptome, to halt cell cycle progression, and to maintain an ideal environment for manufacturing infectious virions. Refer to individual Series. This SuperSeries is composed of the following subset Series: GSE24585: Expression profiling of host genes modulated by Epstein-Barr virus (EBV) Rta in HEK293 cells GSE24586: Expression profiling of host genes modulated by Epstein-Barr virus Rta in nasopharyngeal carcinoma cells
2011-03-31 | E-GEOD-24587 | biostudies-arrayexpress
Project description:The oral cavity has previously been identified as the major site for transmission of Kaposi’s sarcoma-associated herpesvirus (KSHV), but how KSHV establishes infection and replication in the oral epithelia remains unclear. Here, we report a KSHV spontaneous lytic replication model using fully differentiated, three-dimensional (3D) oral epithelial organoids at an air-liquid interface (ALI). This model revealed that KSHV infected the oral epithelia when the basal epithelial cells were exposed by damage. Unlike two-dimensional (2D) cell culture, 3D oral epithelial organoid ALI culture allowed high levels of spontaneous KSHV lytic replication, where lytically replicating cells were enriched at the superficial layer of epithelial organoid. Single cell RNA sequencing (scRNAseq) showed that KSHV infection induced drastic changes of host gene expression in infected as well as uninfected cells at the different epithelial layers, resulting in altered epithelial differentiation and morphogenesis. Moreover, we identified a unique population of infected cells containing lytic gene expression at the KSHV K2-K5 gene locus and distinct host and viral gene expression compared to latency or lytic replication. This study demonstrates an in vitro 3D epithelial organoid ALI culture model that recapitulates KSHV infection in the oral cavity, where KSHV undergoes the epithelial differentiation-dependent spontaneous lytic replication with a unique cell population carrying distinct viral gene expression.
2022-07-28 | GSE184257 | GEO