Modulation of the immune system by Kaposi's sarcoma-associated herpesvirus

Aresté, Cristina; Blackbourn, David J.

doi:10.1016/j.tim.2008.12.001

Cited by 71 publications

(61 citation statements)

References 78 publications

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“…Such prevalent amounts of antisense transcripts have a great potential to form dsRNAs. These observations may help to explain why KSHV has evolved numerous countermeasures to deal with the cellular interferon immune response that can be activated by dsRNA (Coscoy 2007;Areste and Blackbourn 2009;Bisson et al 2009;Lee et al 2009). In addition, these results suggest that the virus will have to deal with the issue of RNA polymerase exclusion and may, in fact, use antisense transcription to regulate viral gene expression.…”

Section: Lytic Replication Triggers Antisense Transcription That Is Dmentioning

confidence: 98%

Small RNA profiling reveals antisense transcription throughout the KSHV genome and novel small RNAs

Lin¹,

Kincaid²,

Arasappan³

et al. 2010

RNA

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Kaposi's sarcoma-associated herpesvirus (KSHV) is a human tumor virus that encodes 12 precursor microRNAs (pre-miRNAs) that give rise to 17 different known~22-nucleotide (nt) effector miRNAs. Like all herpesviruses, KSHV has two modes of infection: (1) a latent mode whereby only a subset of viral genes are expressed and (2) a lytic mode during which the full remaining viral genes are expressed. To date, KSHV miRNAs have been mostly identified via analysis of cells that are undergoing latent infection. Here, we developed a method to profile small RNAs (~18-75 nt) from populations of cells undergoing predominantly lytic infection. Using two different next-generation sequencing platforms, we cloned and sequenced both premiRNAs and derivative miRNAs. Our analysis shows that the vast majority of viral and host 5p miRNAs are co-terminal with the 59 end of the cloned pre-miRNAs, consistent with both being defined by microprocessor cleavage. We report the complete repertoire (25 total) of 5p and 3p derivative miRNAs from all 12 previously described KSHV pre-miRNAs. Two KSHV premiRNAs, pre-miR-K12-8 and pre-miR-K12-12, encode abundant derivative miRNAs from the previously unreported strands of the pre-miRNA. We identify several novel small RNAs of low abundance, including viral miRNA-offset-RNAs (moRNAs), and antisense viral miRNAs (miRNA-AS) that are encoded antisense to previously reported KSHV pre-miRNAs. Finally, we observe widespread antisense transcription relative to known coding sequences during lytic replication. Despite the enormous potential to form double-stranded RNA in KSHV-infected cells, we observe no evidence for the existence of abundant viral-derived small interfering RNAs (siRNAs).

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Section: Lytic Replication Triggers Antisense Transcription That Is Dmentioning

confidence: 98%

Small RNA profiling reveals antisense transcription throughout the KSHV genome and novel small RNAs

Lin¹,

Kincaid²,

Arasappan³

et al. 2010

RNA

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“…All of them are linked to viral maintenance and to the perturbation of the host immune response (Dourmishev et al, 2003;zur Hausen, 2006;Areste´and Blackbourn, 2009). In particular, several of these proteins (LANA, v-cyclinD, vFLIP and kaposin) can affect the main tumorigenic pathways involved in regulating important tumor suppressors and oncogenic genes in mammals (Godden-Kent et al, 1997;Friborg et al, 1999;Radkov et al, 2000;Fujimuro et al, 2003;Guasparri et al, 2004;McCormick and Ganem, 2005;Bubman et al, 2007;Di Bartolo et al, 2008).…”

Section: Viral Epigenomes In Human Tumorigenesis Af Fernandez and M Ementioning

confidence: 99%

Viral epigenomes in human tumorigenesis

Fernández

Esteller

2010

Oncogene

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Viruses are associated with 15-20% of human cancers worldwide. In the last century, many studies were directed towards elucidating the molecular mechanisms and genetic alterations by which viruses cause cancer. The importance of epigenetics in the regulation of gene expression has prompted the investigation of virus and host interactions not only at the genetic level but also at the epigenetic level. In this study, we summarize the published epigenetic information relating to the genomes of viruses directly or indirectly associated with the establishment of tumorigenic processes. We also review aspects such as viral replication and latency associated with epigenetic changes and summarize what is known about epigenetic alterations in host genomes and the implications of these for the tumoral process. The advances made in characterizing epigenetic features in cancer-causing viruses have improved our understanding of their functional mechanisms. Knowledge of the epigenetic changes that occur in the genome of these viruses should provide us with markers for following cancer progression, as well as new tools for cancer therapy.

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“…36,37). Only a limited number of viral proteins was reported to interfere with the function of activated IRF-3 in the nucleus (38)(39)(40)(41)(42)(43)(44)(45)(46)(47)(48)(49)(50)(51).…”

mentioning

confidence: 99%

Human Bocavirus NP1 Inhibits IFN-β Production by Blocking Association of IFN Regulatory Factor 3 with IFNB Promoter

Zhang

Zheng

Luo

et al. 2012

The Journal of Immunology

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Human bocavirus (HBoV) mainly infects young children. Although many infected children suffer from respiratory or gastroenteric tract diseases, an association between HBoV and these diseases is not definite. Because modulation of type I IFN is crucial for viruses to establish efficient replication, in this study, we tested whether HBoV modulates type I IFN production. We observed that a nearly full-length HBoV clone significantly reduced both Sendai virus (SeV)- and poly(deoxyadenylic-thymidylic) acid-induced IFN-β production. Further study showed that NP1 blocked IFN-β activation in response to SeV, poly(deoxyadenylic-thymidylic) acid, and IFN-β pathway inducers, including retinoic acid-inducible protein I, mitochondrial antiviral signaling protein, inhibitor of κB kinase ε, and TANK-binding kinase 1. In addition, NP1 interfered with IRF-3–responsive PRD(III-I) promoter activated by SeV and a constitutively active mutant of IRF-3 (IRF-3/5D). Although NP1 suppressed the IRF-3 pathway, it did not affect IRF-3 activation processes, including phosphorylation, dimerization, and nuclear translocation. Coimmunoprecipitation assays confirmed the interaction between NP1 and IRF-3. Additional deletion mutagenesis and coimmunoprecipitation assays revealed that NP1 bound to the DNA-binding domain of IRF-3, resulting in the interruption of an association between IRF-3 and IFNB promoter. Altogether, our results indicate that HBoV NP1 blocks IFN production through a unique mechanism. To our knowledge, this is the first study to investigate the modulation of innate immunity by HBoV. Our findings suggest a potential immune-evasion mechanism used by HBoV and provide a basis for better understanding HBoV pathogenesis.

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Modulation of the immune system by Kaposi's sarcoma-associated herpesvirus

Cited by 71 publications

References 78 publications

Small RNA profiling reveals antisense transcription throughout the KSHV genome and novel small RNAs

Small RNA profiling reveals antisense transcription throughout the KSHV genome and novel small RNAs

Viral epigenomes in human tumorigenesis

Human Bocavirus NP1 Inhibits IFN-β Production by Blocking Association of IFN Regulatory Factor 3 with IFNB Promoter

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