Submitted December 22, 2008
Accepted March 18, 2009
HIV-1 infected dendritic cells show two phases of gene expression changes with lysosomal enzyme activity decreased during the second phase
Andrew N Harman, Marianne Kraus, Chris R Bye, Karen Byth, Stuart G Turville, Owen Tang, Sarah K Mercier, Najla Nasr, Josh L Stern, Barry Slobedman, Christoph Driessen, and Anthony L Cunningham*
Centre for Virus Research, Westmead Millennium Institute, Westmead NSW, Sydney, Australia
Experimental Oncology, Departement of Oncology/Hematology, Cantonal Hospital, St. Gallen, Switzerland
* Corresponding author; email: tony_cunningham{at}wmi.usyd.edu.au.
Dendritic cells (DC) play a key role in the pathogenesis of HIV infection. HIV interacts with these cells through two pathways in two temporal phases, initially via endocytosis and then via de novo replication. Here the transcriptional response of human DCs to HIV-1 was studied in these phases and at different stages of the virus replication cycle using purified HIV-1 envelope proteins, inactivated and viable HIV-1. No differential gene expression was detected in response to envelope. However >100 genes were differentially expressed in response to entry of viable and inactivated HIV in the first phase. A completely different set of genes were differentially expressed in the second phase, predominantly in response to viable HIV-1, including up regulation of immune regulation genes while genes encoding lysosomal enzymes were downregulated. Cathepsins B, C, S and Z RNA and protein decreased while cathepsin L was increased probably reflecting a concomitant decrease in cystatin C. The net effect was markedly diminished cathepsin activity likely to result in enhanced HIV-1 survival and transfer to contacting T lymphocytes but decreased HIV-1 antigen processing and presentation to these T cells.
