6 fold, 2 to 3 fold, and 2. 4 to 2. 6 fold respectively. TAK 779 prevented HIV induced phosphorylation of these cytoskeleton associated proteins during monocyte endothelial interactions. Ingenuity pathway analysis of differentially expressed and phosphorylated proteins showed that the major bio logical functions associated with these Epigenetic Reader Do cytoskeleton associated proteins and phosphorylation network included cellular assembly and organization, cellular movement, cell morphology, post translational modification, cell cycle and cell to cell signaling. Canonical pathways activated in HIV infected monocytes co cultured with HBMEC included chemokine and integ rin Inhibitors,Modulators,Libraries signaling, and cell junction signaling.

Confirmation of non productive HIV 1 infection of monocytes It is known that HIV 1 does not productively infect hu man monocytes, and even for monocytes derived macro phages, productive infection is often seen from day 3 post infection. To determine whether non productive Inhibitors,Modulators,Libraries infection of monocytes occur, we analyzed gag and tat mRNA, Inhibitors,Modulators,Libraries and gp120 expression in freshly elutriated and HIV exposed monocytes cultured 2 to 48 hours in media with and with out human recombinant macrophage colony stimulating factor. Quantitative real time PCR for HIV 1 gag mRNA showed that HIV 1 gag mRNA was present in monocytes from 2 hours post elutri ationinfection, with more gag copies numbers in mono cytes cultured in media without MCSF, compared to monocytes cultured in media con taining MCSF. Gag mRNA copy numbers decreased over time but was still detectable in infected cells.

Reverse transcription PCR targeting tat mRNA also showed de tectable tat mRNA in both monocytes cultured in media with and without MCSF from 2 hours post elutriationin fection. Immunofluorescence analysis using gp120 monoclo nal antibodies Inhibitors,Modulators,Libraries also showed positive staining for HIV 1 gp120 in monocytes from 2 hours post elutriationinfection. Increased transcription of cortactin and Rac1, and Rac1 activation in brain tissues of HIV infected patients To determine whether our in vitro findings correlated with changes in HIV infected humans, we analyzed brain tissues of 12 HIV 1,2 seronegative control subjects, 9 HIV 1 seropositive patients without evidence of HIVE, and 10 HIV 1 seropositive patients with HIVE and HAND. All brain tissues were from the cortex region, with 28 of the 31 samples from the frontal cortex, 2 samples from the parietal cortex, and 1 sample from the temporal cortex.

Table Inhibitors,Modulators,Libraries 3 shows the age, gender, clinical history, post mortem interval between the time of death and aut opsy, and a summary of post mortem findings for all 31 human subjects. For seronegative controls, HIV infected, and HIVE patients, the age ranges in years were respect ively 32 to 72, 27 to 54, ref 1 and 30 to 52. For seronegative controls, HIV infected, and HIVE patients, the PMI ranges in hours were respectively 3 to 8. 5, 2. 75 to 15, and 4 to 21.