PMID- 19436054 OWN - NLM STAT- MEDLINE DCOM- 20090724 LR - 20211020 IS - 1528-0020 (Electronic) IS - 0006-4971 (Print) IS - 0006-4971 (Linking) VI - 114 IP - 1 DP - 2009 Jul 2 TI - HIV-1-infected dendritic cells show 2 phases of gene expression changes, with lysosomal enzyme activity decreased during the second phase. PG - 85-94 LID - 10.1182/blood-2008-12-194845 [doi] AB - Dendritic cells (DCs) play a key role in the pathogenesis of HIV infection. HIV interacts with these cells through 2 pathways in 2 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, and inactivated and viable HIV-1. No differential gene expression was detected in response to envelope. However, more than 100 genes were differentially expressed in response to entry of viable and inactivated HIV-1 in the first phase. A completely different set of genes was differentially expressed in the second phase, predominantly in response to viable HIV-1, including up-regulation of immune regulation genes, whereas genes encoding lysosomal enzymes were down-regulated. Cathepsins B, C, S, and Z RNA and protein decreased, whereas 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. FAU - Harman, Andrew N AU - Harman AN AD - Centre for Virus Research, Westmead Millennium Institute, Sydney, Australia. FAU - Kraus, Marianne AU - Kraus M FAU - Bye, Chris R AU - Bye CR FAU - Byth, Karen AU - Byth K FAU - Turville, Stuart G AU - Turville SG FAU - Tang, Owen AU - Tang O FAU - Mercier, Sarah K AU - Mercier SK FAU - Nasr, Najla AU - Nasr N FAU - Stern, Josh L AU - Stern JL FAU - Slobedman, Barry AU - Slobedman B FAU - Driessen, Christoph AU - Driessen C FAU - Cunningham, Anthony L AU - Cunningham AL LA - eng GR - R01 DE015512/DE/NIDCR NIH HHS/United States GR - R01 GM099705/GM/NIGMS NIH HHS/United States GR - R01 DE015512-01/DE/NIDCR NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20090512 PL - United States TA - Blood JT - Blood JID - 7603509 RN - 0 (Cystatins) RN - 0 (DNA Primers) RN - 0 (HIV Envelope Protein gp120) RN - 0 (gp120 protein, Human immunodeficiency virus 1) RN - EC 3.4.- (Cathepsins) SB - IM MH - Antigen Presentation MH - Base Sequence MH - Cathepsins/genetics/metabolism MH - Cystatins/genetics/metabolism MH - DNA Primers/genetics MH - Dendritic Cells/immunology/metabolism/*virology MH - Gene Expression MH - Genes, Viral MH - HIV Envelope Protein gp120/physiology MH - HIV-1/*genetics/*pathogenicity/physiology MH - Humans MH - In Vitro Techniques MH - Kinetics MH - Lysosomes/enzymology/genetics MH - Models, Biological MH - Oligonucleotide Array Sequence Analysis MH - T-Lymphocytes/virology MH - Virus Internalization MH - Virus Replication PMC - PMC2710958 EDAT- 2009/05/14 09:00 MHDA- 2009/07/25 09:00 PMCR- 2010/07/02 CRDT- 2009/05/14 09:00 PHST- 2009/05/14 09:00 [entrez] PHST- 2009/05/14 09:00 [pubmed] PHST- 2009/07/25 09:00 [medline] PHST- 2010/07/02 00:00 [pmc-release] AID - S0006-4971(20)37140-8 [pii] AID - 2008/194845 [pii] AID - 10.1182/blood-2008-12-194845 [doi] PST - ppublish SO - Blood. 2009 Jul 2;114(1):85-94. doi: 10.1182/blood-2008-12-194845. Epub 2009 May 12.