HIV Latency: Molecular Mechanisms Eric Verdin, MD Associate Director and Senior Investigator.

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Presentation transcript:

HIV Latency: Molecular Mechanisms Eric Verdin, MD Associate Director and Senior Investigator

HIV Latency: Establishment vs. Maintenance

HIV Latency at the Molecular Level

(Vorinostat, Romidepsin)

HIV Latency: Establishment vs. Maintenance shRNA Screen for Cellular Genes that Control HIV Latency

shRNA Screen Experimental Plan

Non validated shRNAs 25 shRNA/gene 18,900 human genes 1000 shRNA controls 495,000 shRNAs total Duplicate Screen shRNA Screen Vector and Library Bassik MC, Kampmann M, et al Cell Feb 14;152(4):

shRNA Screen Experimental Plan

Protein Complexes That Control HIV Latency Latency Promoting Latency Suppressing

TOR Signaling

TOR Signaling and CD4 T Cell Subsets

Treg Induction and HIV Latency

Treg Induction Is Associated with Increased HIV Latency

TOR Signaling in T cells

Inhibition of m-TOR Suppresses Reactivation From Latency

Title Box HDACi Prostratin

Title Box

V ERDIN L AB - G LADSTONE /UCSF Shweta Hakre Leonard Chavez Kotaro Shirakawa Vincenzo Calvanese Emilie Bativelli Matthew Dahabieh S ILICIANO L AB - J OHNS H OPKIN Nina Hosmane Robert Siliciano W EISSMAN L AB -UCSF Jonathan Weissman Martin Kampmann Michael Bassik K ROGAN L AB -UCSF Nevan Krogan Erik Verschueren Natalie Gulbahce G REENE L AB - G LADSTONE /UCSF Jonathan Chan Warner Greene

Title Box

Infection Trajectories Leading to Latent HIV

The p-TEFb Complex Controls HIV Latency Latency Promoting Latency Suppressing

The PRC2 Complex Controls HIV Latency Latency Promoting Latency Suppressing

The mTOR-TGFβ Pathways Control HIV Latency Latency Promoting Latency Suppressing