HIV-1-infected dendritic cells show 2 phases of gene expression changes, with lysosomal enzyme activity decreased during the second phase.
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.
Centre for Virus Research, Westmead Millennium Institute, Sydney, Australia.
Andrew N
AN
Harman
Marianne
M
Kraus
Chris R
CR
Bye
Karen
K
Byth
Stuart G
SG
Turville
Owen
O
Tang
Sarah K
SK
Mercier
Najla
N
Nasr
Josh L
JL
Stern
Barry
B
Slobedman
Christoph
C
Driessen
Anthony L
AL
Cunningham
D017951:Antigen Presentation; D001483:Base Sequence; D002403:Cathepsins / Q000235:genetics / Q000378:metabolism; D015891:Cystatins / Q000235:genetics / Q000378:metabolism; D017931:DNA Primers / Q000235:genetics; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism / Q000821:virology*; D015870:Gene Expression; D005814:Genes, Viral; D015699:HIV Envelope Protein gp120 / Q000502:physiology; D015497:HIV-1 / Q000235:genetics* / Q000472:pathogenicity* / Q000502:physiology; D006801:Humans; D066298:In Vitro Techniques; D007700:Kinetics; D008247:Lysosomes / Q000201:enzymology / Q000235:genetics; D008954:Models, Biological; D020411:Oligonucleotide Array Sequence Analysis; D013601:T-Lymphocytes / Q000821:virology; D053586:Virus Internalization; D014779:Virus Replication
D015891:Cystatins; D017931:DNA Primers; D015699:HIV Envelope Protein gp120; C514793:gp120 protein, Human immunodeficiency virus 1; D002403:Cathepsins