Presentation on host virus interaction(2008432018)
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The presentation discusses the role of microRNAs (miRNAs) in host-virus interactions and their implications. Human miRNAs can target conserved regions in viral genes, while some viruses encode miRNAs that may influence cellular processes and lead to oncogenesis. Analysis of miRNA levels in humans may serve as molecular markers for disease susceptibility and prognosis. The development of artificial miRNAs could provide a therapeutic approach for modulating viral infections.
![References
1.Lecellier CH, et al. A cellular microRNA mediates antiviral defense in
human cells. Science 2005;308:557–560. [PubMed: 15845854]
2.Pedersen IM, et al. Interferon modulation of cellular microRNAs as an
antiviral mechanism. Nature 2007;449:919–922. [PubMed:17943132]
3.Bartel DP: MicroRNAs: genomics, biogenesis, mechanism,
and function. Cell 2004, 116:281-297.
4.Esquela-Kerscher A, Slack FJ: Oncomirs [mdash] microRNAs with a role in
cancer. Nat Rev Cancer 2006, 6:259-269.
5.John B, Enright AJ, Aravin A, Tuschl T, Sander C, Marks DS: Human
MicroRNA targets. PLoS Biol 2004, 2:e363.
6.Browne, E.P., Li, J., Chong, M., and Littman, D.R. (2005) Virus–host
interactions: new insights from the small RNA world. Genome Biol 6: 238.
7.Nair,V. and Zavolan,M. (2006) Virus-encoded microRNAs: novel
regulators of gene expression. Trends Microbiol., 14, 169–175.
8. Cullen,B.R. (2006) Viruses and microRNAs. Nature Genet., 38, S25–S30.](https://image.slidesharecdn.com/presentationonhost-virusinteraction2008432018-120831004911-phpapp01/85/Presentation-on-host-virus-interaction-2008432018-17-320.jpg)
Presentation on host virus interaction(2008432018)
- 1. WELCOME TO MY PRESENTATION Molecular Players in Host-Virus Interaction: Novel roles for microRNAs Presented by: Jahed Ahmed Reg. No. 2008432018
- 2. Virus - Host Interaction Immune Persistance response Cell Virus signalling infection Clearance Apoptosis Fig.:Viruses interact with three basic host responses
- 3. Host-Virus interaction 1. Essential for virus function -Replication -Movement 2. Host Resistance Interactions 3. Inconsequential to virus function Virus Host Disturbance in the host physiology Proteome Transcriptome Disease/Resistance Metabolic Pathways etc.
- 4. MicroRNAs • microRNAs (miRNAs) are small noncoding RNAs of ∼ 22-nt length that serve as posttranscriptional regulators of gene expression in higher eukaryotes • First identified in 1993 in C. elegans by Ambross • But in 2001 it got the attention of researchers when it is found to be related in cancer • These small non-coding RNAs can contribute to the repertoire of host pathogen interactions during viral infection • Host-cellular miRNAs modulating the expression of various viral genes, thereby playing a pivotal role in the host–pathogen interaction network
- 5. MicroRNAs • Viruses have evolved highly sophisticated gene- silencing mechanisms to evade host-immune response • Recent reports indicate that virus too encode miRNAs that protect them against cellular antiviral response • The host–virus interaction at the molecular level lead us toward possible explanations to viral tropism, latency and oncogenesis along with the development of an effective, durable and nontoxic antiviral therapy • It is reported that least 30% human genes are regulated by miRNAs
- 6. Biogenesis of MicroRNAs MicroRNAs are transcribed by the RNA polymerase II enzyme to produce a primary-microRNA pri-microRNAs form specific hairpin secondary structures and enter a microprocessor complex The pre-miRNAs are then transported to the cytoplasm In the cytoplasm, pre-miRNAs are further processed to a short double strand miRNA duplex by Dicer Then association with RISC (RNA induced silencing complex) 2 mechanisms of action: inhibition of translation OR mRNA cleavage
- 7. microRNA Biogenesis and action Dicer miRNA-miRNA* pre-miRNA miRNA with RISC Messenger RNA AAAAA Exportin 5 Drosha/Pasha Transcript Degradation pri-miRNA Transcript P Bodies RNAPol II Polypeptide Scaria et al. Retrovirology 2006
- 8. Model of microRNA mediated host-virus crosstalk MODEL-II MODEL-III DICER RISC MODEL-IV MODEL-I EXPORTIN DROSHA/P ASHA Host Transcript Host Transcript Polypeptide Viral Transcript Viral Transcript RNAPol II Scaria et al. Retrovirology 2006
- 9. Five Human microRNAs can possibly target HIV genes
- 10. Human microRNAs target HA and PB2 genes in Influenza A/H5N1 genome Polymerase PB2 SEGMENT1 hsa-mir-507 responsible for RNA replication and transcription Hemagglutinin (HA) SEGMENT4 hsa-mir-136 facilitates entry of the virus into the cell
- 11. Mechanisms of microRNAs in viral oncogenesis Altered host gene expression Viral encoded Viral genome microRNAs integration and mutations Regulatory dysfunction Oncogenesis Virus induced epigenetic changes Viral suppression of RNAi Altered host microRNA expression Scaria and Jadhav, Retrovirology, 2007
- 12. Scaria and Jadhav, Retrovirology. 2007 Nov 24;4(1):82 Host-Pathogen Interaction: An integrative Model for microRNAs in viral oncogenesis Virus encoded proteins and cell signaling mediated by viral PROTEIN INTERACTION AND SIGNALLING infections microRNA mediated regulation Virus encoded POST-TRANSCRIPTIONAL REGULATION microRNAs Virus encoded suppressors of RNAi SPLICING AND RNA EDITING Viral encoded transcriptional regulators TRANSCRIPTIONAL REGULATION Viral Genome integration GENOME STRUCTURE AND CHROMATIN ORGANISATION Chromosomal GENOME SEQUENCE Instabilities Epigenetic Changes
- 13. Viral miRNAs-Regulating Gene Expression: Fig.: Effects of virus-encoded microRNAs on viral and cellular transcripts.
- 14. Future Prospects •MicroRNA as a novel arm of gene expressional regulation tool has great potential to be employed in drug development •miRNA research may provide us more insights and improved understanding towards miRNA biogenesis, function and particularly their association with molecular pathogenesis of a variety of complex diseases including cancer, heart diseases, chronic viral infections, immune disorders, neurodegenerative disease and metabolic diseases. •Identify oncogenic miRNAs, and viral encoded miRNAs, which may key factors for viral replication and latency and the ideal targets for developing therapeutics •Design of artificial antiviral microRNAs (amiRNAs) which may be used as therapeutics
- 15. Conclusions •The integral role of miRNAs in controlling various complex regulatory networks within a cell is gradually coming into limelight. It is seen that host-encoded miRNAs have both positive and negative modulatory effect on viral replication. •Virus uses their own miRNA induced gene-silencing machinery to protect them against the cellular antiviral RNAi response and may even affect cellular gene expression. •miRNA-induced gene-silencing approach holds great promise for selectively inhibiting virus-specific genes or host genes for the treatment of viral infections. •The miRNA-mediated host–virus interaction at the molecular level, which will lead toward the development of effective non- toxic antiviral therapy.
- 16. Summary Human microRNAs have conserved targets in viral genes Viral microRNAs may miRNA-miRNA* influence cellular biological processes Dicer resulting in oncogenesis pre-miRNA Exportin 5 miRNA with RISC Drosha miRNA levels in Human Transcript can be used as a Transcript molecular marker for pri-miRNA disease susceptibility and prognosis. RNAPol II P Bodies Degradation NUCLEUS Polypeptide Synthetic/Artifical CYTOPLASM miRNAs or miRNA analogs may be used as therapeutics
- 17. References 1.Lecellier CH, et al. A cellular microRNA mediates antiviral defense in human cells. Science 2005;308:557–560. [PubMed: 15845854] 2.Pedersen IM, et al. Interferon modulation of cellular microRNAs as an antiviral mechanism. Nature 2007;449:919–922. [PubMed:17943132] 3.Bartel DP: MicroRNAs: genomics, biogenesis, mechanism, and function. Cell 2004, 116:281-297. 4.Esquela-Kerscher A, Slack FJ: Oncomirs [mdash] microRNAs with a role in cancer. Nat Rev Cancer 2006, 6:259-269. 5.John B, Enright AJ, Aravin A, Tuschl T, Sander C, Marks DS: Human MicroRNA targets. PLoS Biol 2004, 2:e363. 6.Browne, E.P., Li, J., Chong, M., and Littman, D.R. (2005) Virus–host interactions: new insights from the small RNA world. Genome Biol 6: 238. 7.Nair,V. and Zavolan,M. (2006) Virus-encoded microRNAs: novel regulators of gene expression. Trends Microbiol., 14, 169–175. 8. Cullen,B.R. (2006) Viruses and microRNAs. Nature Genet., 38, S25–S30.