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786 South Carolina Center for Biotechnology Claflin University

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Title: 786 South Carolina Center for Biotechnology Claflin University


1
786South Carolina Center for BiotechnologyClafli
n University
  • Omar Bagasra, M.D., Ph.D
  • Professor Director
  • Email obagasra_at_claflin.edu

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

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 al et 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 Med 7, 1232-5.
  • Xiang, J. et. al. (2001) Effect of coinfection
    with GB virus C on survival among patients with
    HIV infection. N Engl J Med 345, 707-14.

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 gt200 motifs

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

7
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8
What may be the mechanism?
  • Hypotheses
  • RNAi
  • Triplex forming complex

9
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10
Triplex are favored byC.CG and T.ATMotifs
11
Design of four miRNA with TF capacity utilizing
C.CG and T.AT algorithm
12
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

13
Evidence of Triplex Formation
14
pSuper.neo.vector
15
19bp dsRNA expression system
16
Experimental Design
17
HIV-1 p24 ELISA
18
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19
Syncytia Formation
20
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22
Mode of Transfer of miRNAs
23
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24
Conclusion
  • miRNAs play a central role in retroviral latency
    and their silencing.
  • HIV-1 specific designer miRNA can block its
    replication in vitro.

25
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
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