HIV-1-infected dendritic cells show 2 phases of gene expression changes, with lysosomal enzyme activity decreased during the second phase

Blood. 2009 Jul 2;114(1):85-94. doi: 10.1182/blood-2008-12-194845. Epub 2009 May 12.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigen Presentation
  • Base Sequence
  • Cathepsins / genetics
  • Cathepsins / metabolism
  • Cystatins / genetics
  • Cystatins / metabolism
  • DNA Primers / genetics
  • Dendritic Cells / immunology
  • Dendritic Cells / metabolism
  • Dendritic Cells / virology*
  • Gene Expression
  • Genes, Viral
  • HIV Envelope Protein gp120 / physiology
  • HIV-1 / genetics*
  • HIV-1 / pathogenicity*
  • HIV-1 / physiology
  • Humans
  • In Vitro Techniques
  • Kinetics
  • Lysosomes / enzymology
  • Lysosomes / genetics
  • Models, Biological
  • Oligonucleotide Array Sequence Analysis
  • T-Lymphocytes / virology
  • Virus Internalization
  • Virus Replication

Substances

  • Cystatins
  • DNA Primers
  • HIV Envelope Protein gp120
  • gp120 protein, Human immunodeficiency virus 1
  • Cathepsins