Sonia Gauthier and Michel J. Tremblay

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• Sonia Gauthier and Michel J. Tremblay

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Introduction GALT and HIV-1

• Transmission
• Mother-to-child
• Intestinal
• CD4 depletion during primo-infection
• Majority of CD4-T cells are CCR5 positive
• 70
• Viral reservoir
• Viral RNA detectable on successful HAART

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Cytokines in the GALT environment
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Effect of different cytokines on HIV-1
replication in HT-29 cells


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Effect of different cytokines on HIV-1
transactivation in HT-29 cells



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IL-4 modulates GalCer and CXCR4 expression on
HT-29 cells


GalCer expression
CXCR4 expression
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IL-4 differently modulates VSV-G and
NDK-Env-mediated virus entry


NDK-Env pseudotyped virus
VSV- G pseudotyped virus
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IL-4 does not affect VSV-G pseudotyped viruses
fusion

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IL-4 inhibits VSV-G pseudotyped viruses




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IL-4 inhibits retrotranscription of VSV-G
pseudotyped viruses


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Conclusions

• IL-1a, IL-ß and TNF-a stimulated viral
  transcription in HT-29 cells
• IL-4 inhibits HIV-1 replication in HT-29 cells
• Downregulation of GalCer and CXCR4
• Inhibition of retrotranscription or earlier step
  in viral cycle
• Inhibition is dose-dependent
• Maximal inhibition at 1U/ml (35pg/ml)

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Acknowledgements

• Dr Michel J. Tremblay, Principal investigator
• All Dr Tremblay team members
• Dr Corinne Barat
• Dr Michel Ouellet
• Dr Mélanie Tardif
• CIHR Doctoral Research Award