786 South Carolina Center for Biotechnology Claflin University

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786South Carolina Center for BiotechnologyClafli
n University

• Omar Bagasra, M.D., Ph.D
• Professor Director
• Email obagasra_at_claflin.edu

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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
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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

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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.

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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

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Are miRNAs shared between HIV and other
co-infecting viruses?

• Are these mutually homologous miRNAs play a
  protective role (s)?

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What may be the mechanism?

• Hypotheses
• RNAi
• Triplex forming complex

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

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Evidence of Triplex Formation
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pSuper.neo.vector
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19bp dsRNA expression system
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Experimental Design
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HIV-1 p24 ELISA
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Syncytia Formation
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Mode of Transfer of miRNAs
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Conclusion

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

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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