i. Regulation of HIV transcription and mechanisims of latency. ii. viral – host interactions. iii.Use of lentiviruses for targeting specific cells for gene therpy application. • Dan Levy - Role of SETD6 in modulating HIV latency. • Alon Freidman – Targeting of lentiviruses to specific cells. Lost in transcription – mechanisms that drive HIV latency Ongoing Projects going Collaborations
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I.Regulation of HIV transcription and mechanisims of latency. ii.viral – host interactions. iii.Use of lentiviruses for targeting specific cells for gene.
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i. Regulation of HIV transcription and mechanisims of latency.
ii. viral – host interactions.iii. Use of lentiviruses for targeting specific cells for gene
therpy application.
• Dan Levy - Role of SETD6 in modulating HIV latency.
• Alon Freidman – Targeting of lentiviruses to specific cells.
Lost in transcription – mechanisms that drive HIV latency
Ongoing Projects
Ongoing Collaborations
The Problem - latency is a block for HIV eradication
Latency - a reversibly low-productive state of infection, where infected cells retain the capacity to fully re-emerge and produce de-novo viral particles
New HIV infections
AIDS- related deaths
HAART
Pe
ople
Total: 34.2 million
HIV infected
Pe
ople
Latent HIV reservoirs that
are refractory to therapy
What are the molecular mechanisms that regulate HIV latency?
Ways to reactivate latent HIV and eliminate viral reservoirs with
HAART?
Regulation of HIV transcriptional activation
Role of Positive transcription elongation b -PTEFb
HYPOTHESIS
NF-ATTAFs…
Active State
HIV Provirus
gag
poltatrev
env nefvif
vpuvpr
5’LTR
Latent StateCondensed chromatin
HDACs
YY1/LSFCBF-1AP4
NF-AT
TAFs…
CpG islands
metH3K27
me3
SWI/SNFremodeling
HIV provirusCCR5/CXCR4 CD4
met met
P-TEFbHATs
HKMT/
SUV39H1
G9a
NF-B
Ac3’LTR Ac
Ac
met
nuc1
Ac
PRC1/2Remodeling
EZH2
NF-B
A
B
H3K9me2
Latency corresponds with transcription activation and chromatin state