Towards Better Understanding of KSHV Life Cycle: from Transcription and Posttranscriptional Regulations to Pathogenesis

Yan, Lijun; Majerčiak, Vladimır; Zheng, Zhi-Ming; Lan, Ke

doi:10.1007/s12250-019-00114-3

Cited by 60 publications

(71 citation statements)

References 342 publications

(415 reference statements)

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“…gB, gH, and gL) (Veettil et al, 2014). In de novo KSHV-infected cells, viral genome rapidly circularizes in the nucleus, where it is maintained in a latent state as a chromatinized plasmid; in these conditions, virions are not produced, and only a subset of genes are expressed (Yan et al, 2019). As a consequence of environmental changes and physiological stimuli (e.g.…”

Section: Kaposi's Sarcoma-associated Herpesvirus (Kshv)mentioning

confidence: 99%

“…As a consequence of environmental changes and physiological stimuli (e.g. oxidative stress, hypoxia, and autophagy activation), KSHV-infected cells reactivate the viral cycle promoting the expression of lytic genes in a temporally regulated manner: immediate early, early, and late genes (Yan et al, 2019). Importantly, tumors associated with KSHV infection mostly present with viruses in a latent state; this observation led to the consideration of lytic reactivation not involved in tumorigenesis.…”

Section: Kaposi's Sarcoma-associated Herpesvirus (Kshv)mentioning

confidence: 99%

“…Another protein essential in latency and associated with autophagy inhibition is LANA, the latency-associated nuclear antigen. LANA is essential in maintaining viral genome in a chromatinized state and binds both viral and host DNA to avoid genome loss during mitosis, ensuring viral genome stability and replication (Yan et al, 2019). It has been described that LANA is a viral oncogene, which inhibits p53 activity protecting KSHV-infected cells from death and reduces pRB expression promoting cell proliferation (Friborg et al, 1999;Ganem, 2007).…”

Section: Kaposi's Sarcoma-associated Herpesvirus (Kshv)mentioning

confidence: 99%

See 2 more Smart Citations

Regulation of Autophagy in Cells Infected With Oncogenic Human Viruses and Its Impact on Cancer Development

Vescovo

Pagni

Piacentini

et al. 2020

Front. Cell Dev. Biol.

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About 20% of total cancer cases are associated to infections. To date, seven human viruses have been directly linked to cancer development: high-risk human papillomaviruses (hrHPVs), Merkel cell polyomavirus (MCPyV), hepatitis B virus (HBV), hepatitis C virus (HCV), Epstein-Barr virus (EBV), Kaposi's sarcoma-associated herpesvirus (KSHV), and human T-lymphotropic virus 1 (HTLV-1). These viruses impact on several molecular mechanisms in the host cells, often resulting in chronic inflammation, uncontrolled proliferation, and cell death inhibition, and mechanisms, which favor viral life cycle but may indirectly promote tumorigenesis. Recently, the ability of oncogenic viruses to alter autophagy, a catabolic process activated during the innate immune response to infections, is emerging as a key event for the onset of human cancers. Here, we summarize the current understanding of the molecular mechanisms by which human oncogenic viruses regulate autophagy and how this negative regulation impacts on cancer development. Finally, we highlight novel autophagy-related candidates for the treatment of virus-related cancers. Keywords: oncogenic (or carcinogenic) viruses, autopaghy, human papillomavirus (HPV), Merkel cell polyomavirus (MCPyV), hepatitis B and C viruses (HBV and HCV), Epstein-Barr virus (EBV), Kaposi's sarcomaassociated herpesvirus (KSHV), human T-lymphotropic virus 1 (HTLV-1)

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Section: Kaposi's Sarcoma-associated Herpesvirus (Kshv)mentioning

confidence: 99%

Section: Kaposi's Sarcoma-associated Herpesvirus (Kshv)mentioning

confidence: 99%

Section: Kaposi's Sarcoma-associated Herpesvirus (Kshv)mentioning

confidence: 99%

See 1 more Smart Citation

Regulation of Autophagy in Cells Infected With Oncogenic Human Viruses and Its Impact on Cancer Development

Vescovo

Pagni

Piacentini

et al. 2020

Front. Cell Dev. Biol.

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“…HHV8 s miRNAs, transcribed from a~4 kb noncoding sequence located between the orfK12 and orf71 genes, have been reported to inhibit the apoptosis of latently-infected cells by targeting apoptotic genes, and to enhance immune evasion and viral pathogenesis by regulating host immune responses [41]. Finally, HHV8 can occasionally re-enter the lytic phase from the latent state by means of the activation of the replication and transcription activator (RTA) gene orf50 which, beyond the transcriptional regulation and activation of lytic DNA replication, also induces proteasome-mediated degradation of both cellular and viral proteins by its ubiquitin E3 ligase activity [53][54][55].…”

Section: Latent Hhv8 Infectionmentioning

confidence: 99%

Human Herpesvirus 8 and Host-Cell Interaction: Long-Lasting Physiological Modifications, Inflammation and Related Chronic Diseases

2020

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Oncogenic and latent-persistent viruses belonging to both DNA and RNA groups are known to cause serious metabolism alterations. Among these, the Human Herpesvirus 8 (HHV8) infection induces stable modifications in biochemistry and cellular metabolism, which in turn affect its own pathological properties. HHV8 enhances the expression of insulin receptors, supports the accumulation of neutral lipids in cytoplasmic lipid droplets and induces alterations in both triglycerides and cholesterol metabolism in endothelial cells. In addition, HHV8 is also known to modify immune response and cytokine production with implications for cell oxidative status (i.e., reactive oxygen species activation). This review underlines the recent findings regarding the role of latent and persistent HHV8 viral infection in host physiology and pathogenesis.

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“…, 6 found in proteomes that associate with viral genomes during infection with Adenovirus and HSV-1 [48].…”

Section: Introductionmentioning

confidence: 99%

Lytic Reactivation of the Kaposi’s sarcoma-associated herpesvirus (KSHV) is Accompanied by Major Nucleolar Alterations

Atari

Rajan

Chikne

et al. 2020

Preprint

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The nucleolus is a sub-nuclear compartment whose primary function is the biogenesis of ribosomal subunits. Certain viral infections affect the morphology and composition of the nucleolar compartment and influence ribosomal RNA (rRNA) transcription and maturation. However, no description of nucleolar morphology and function during infection with Kaposi's sarcoma-associated herpesvirus (KSHV) is available to date. Using immunofluorescence microscopy, we documented extensive destruction of the nuclear and nucleolar architecture during lytic reactivation of KSHV. This was manifested by redistribution of key nucleolar proteins, including the rRNA transcription factor, UBF, the essential pre-rRNA processing factor Fibrillarin, and the nucleolar multifunctional phosphoproteins Nucleophosmin (NPM1) and Nucleolin. Distinct delocalization patterns were evident; certain nucleolar proteins remained together whereas others dissociated, implying that nucleolar proteins undergo nonrandom programmed dispersion. Of note, neither Fibrillarin nor UBF colocalized with promyelocytic leukemia (PML) nuclear bodies or with the viral protein LANA-1, and their redistribution was not dependent on viral DNA replication or late viral gene expression. No significant changes in pre-rRNA levels and no accumulation of pre-rRNA intermediates were found by RT-qPCR and Northern blot analysis, respectively. Furthermore, fluorescent in situ hybridization (FISH), combined with immunofluorescence, revealed an overlap between Fibrillarin and internal transcribed spacer 1 (ITS1), which represents the primary product of the pre-rRNA, suggesting that the processing of rRNA proceeds during lytic reactivation. Finally, small changes in the levels of pseudouridylation were documented across the rRNA. Taken together, our results suggest that rRNA transcription and processing persist during lytic reactivation of KSHV, yet they may become uncoupled. Whether the observed nucleolar alterations favor productive infection or signify cellular anti-viral responses remains to be determined. Author SummaryWe describe the extensive destruction of the nuclear and nucleolar architecture during lytic reactivation of KSHV. Distinct delocalization patterns are illustrated: certain nucleolar proteins remained associated with each other whereas others dissociated, implying that nucleolar proteins undergo nonrandom , 3 programmed dispersion. Of note, no significant changes in pre-rRNA levels and no accumulation of pre-rRNA intermediates were found, suggesting that pre-RNA transcription and processing continue and could be uncoupled during lytic reactivation. Small changes in the levels of pseudouridylation were documented across the rRNA. Previous studies showed that the different forms of KSHV infection are controlled through cellular and viral functions, which reprogram host epigenetic, transcriptomic, posttranscriptomic and proteomic landscapes. The ability of KSHV to affect the nucleolus and rRNA modifications constitutes a novel interaction network between viral and cellula...

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Towards Better Understanding of KSHV Life Cycle: from Transcription and Posttranscriptional Regulations to Pathogenesis

Cited by 60 publications

References 342 publications

Regulation of Autophagy in Cells Infected With Oncogenic Human Viruses and Its Impact on Cancer Development

Regulation of Autophagy in Cells Infected With Oncogenic Human Viruses and Its Impact on Cancer Development

Human Herpesvirus 8 and Host-Cell Interaction: Long-Lasting Physiological Modifications, Inflammation and Related Chronic Diseases

Lytic Reactivation of the Kaposi’s sarcoma-associated herpesvirus (KSHV) is Accompanied by Major Nucleolar Alterations

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