Targeting the Human CD3γ Gene Promoter By HIV-1 and HTLV-1: Two Distinct Mechanisms Involving A Transcriptional Regulatory Element and Chromatin Remodeling

摘要: Our studies show that HIV-1, HIV-2, and HTLV-I infection all provoke a progressive defect in surface T cell receptor expression. A specific loss of CD3γ transcripts is responsible for the after HIV-1 or HIV-2 infection. Alternatively, while are lost first infection, their reduction followed several months later by CD3δ subsequently CD3e mRNA. Studies transcriptional control revealed parallels with elements regulating gene expression, including downstream element reminiscent HIV TAR. Mutant deletion promoter constructs delimited 53 bp region from major transcription start site as critical positive EMSA experiments demonstrate this sequence functions through an RNA rather than DNA intermediate, which can bind three nuclear protein complexes. Deletion U at +9 +37 kills activity. silencing CD3 locus via chromatin remodeling, characterized increased binding Ikaros to γ enhancer. Expression genes be reactivated infected cells synergistic action histone deactylase inhibitor trichostatin methyltransferase 5-aza-2'-deoxycytidine. The importance viral targeting will discussed. 2005 International Meeting Institute Human Virology Baltimore, USA, 29 August – 2 September