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786 South Carolina Center for Biotechnology Claflin University

786 South Carolina Center for Biotechnology Claflin University. Omar Bagasra, M.D., Ph.D Professor & Director Email: obagasra@claflin.edu.

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786 South Carolina Center for Biotechnology Claflin University

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  1. 786South Carolina Center for BiotechnologyClaflin University Omar Bagasra, M.D., Ph.D Professor & Director Email: obagasra@claflin.edu Omar Bagasra

  2. “An insight into the Inhibition of HIV-1 replication by co-infecting HHV-6, HHV-7 or GVB-C viruses: Role of Mutually Homologous miRNAs in Downregulation of Viral Replication

  3. HIV and Co-infection • HIV infection is often accompanied by co-infection with other pathogens that generally result in accelerating the progression of the disease and in early development of AIDS, i.e. HSV, HHV8, CMV, HPV etc Omar Bagasra

  4. Beneficial Co-infections • However, sometimes certain co-infections can have beneficial effects. Several reports have documented the beneficial effects of two genetically related human herpes viruses-HHV-6, HHV-7- and GBV-C co-infections in HIV-1-infected individuals in terms of significantly longer survival (three times longer) and better prognosis. • Lisco et alet al. Viral interactions in human lymphoid tissue: Human herpesvirus 7 suppresses the replication of CCR5-tropic human immunodeficiency virus type 1 via CD4 modulation. J Virol. 81, 708-17 (2007). • Lusso, P. et al. CD4 is a critical component of the receptor for human herpesvirus 7: Interference with human immunodeficiency virus. Proc. Natl. Acad. Sci. USA 91, 3872-3876 (1994). • Grivel, J. C. et. al. (2001) Suppression of CCR5- but not CXCR4-tropic HIV-1 in lymphoid tissue by human herpesvirus 6. Nat Med7, 1232-5. • Xiang, J. et. al. (2001) Effect of coinfection with GB virus C on survival among patients with HIV infection. N Engl J Med345, 707-14. Omar Bagasra

  5. WHY? • Do miRNAs play any role in this beneficial effect? • If so, How? • Is there a mutual homologies between these four viruses? • One miRNA can target >200 motifs Omar Bagasra

  6. Are miRNAs shared between HIV and other co-infecting viruses? Are these mutually homologous miRNAs play a protective role (s)? Omar Bagasra

  7. What may be the mechanism? Hypotheses RNAi Triplex forming complex Omar Bagasra

  8. Omar Bagasra

  9. Triplex are favored byC+.CG and T.ATMotifs Omar Bagasra

  10. Design of four miRNA with TF capacity utilizing C+.CG and T.AT algorithm

  11. A New Form of Anti-HIV vaccine 1) Use miRNAs that bind firmly with HIV 2) Introduce them via a vector 3) Produce miRNA that can bind HIV-1 3) Use the cells’ internal amplification system to protect the whole human body, including the brain Omar Bagasra

  12. Evidence of Triplex Formation

  13. pSuper.neo.vector

  14. 19bp dsRNA expression system

  15. Experimental Design

  16. HIV-1 p24 ELISA

  17. Omar Bagasra

  18. Syncytia Formation

  19. Omar Bagasra

  20. Mode of Transfer of miRNAs

  21. Conclusion • miRNAs play a central role in retroviral latency and their silencing. • HIV-1 specific designer miRNA can block its replication in vitro. Omar Bagasra

  22. Acknowledgements Mayank Aggarwal Krishna Addanki Muhammad Alsayari, (Currently at Cleveland Clinic) Azima Kalsum Dr. Samina Hassanali Dr. Kuha Mahalingam Dr. Nick Panasik All at South Carolina Center for Biotechnology at Claflin University, SC USA Omar Bagasra

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