Cultured Kaposi's sarcoma tumor cells exhibit a chemokine receptor repertoire that does not allow infection by HIV-1

BMC Dermatol. 2001:1:2. doi: 10.1186/1471-5945-1-2. Epub 2001 Jul 24.

Abstract

Background: HIV-1 is known to play a critical role in the pathogenesis of AIDS-associated Kaposi's sarcoma (KS). However, it remains controversial whether KS cells are target cells for HIV infection. The aim of this study was to investigate the expression of chemokine receptors in KS cell cultures and to determine whether these cells can be infected by HIV-1.

Material and methods: KS-derived cells and KS-Y1 cells were investigated using RT-PCR for the expression of CD4, CCR3, CCR5, CCR8 and CXCR4 mRNA. HIV infectivity of these cells was determined by p24 antigen and HIV-1 RNA production, as well as by HIV-1 DNA integration.

Results and discussion: With the exception of CCR8 which is expressed by KS-derived spindle cell cultures but not by KS-Y1 cells, unstimulated KS cells express no significant levels of CD4, CCR3, CCR5 or CXCR4 mRNA. HIV infectivity assays showed that KS cells were unpermissive to HTLVIIIB and JRFL strains. Although the expression of CXCR4 mRNA could be upregulated by interleukin-1beta, stimulation of KS cells by this cytokine did not allow infection by HIV-1.

Conclusions: This shows that KS cells exhibit a chemokine receptor repertoire that does not allow infection by HIV-1. Other cell types making up KS lesions, such as inflammatory cells, are likely to represent the source of HIV-1 products cooperating to promote KS development and progression.

MeSH terms

  • Actins / metabolism
  • CD4 Antigens / metabolism
  • DNA, Viral / isolation & purification
  • Disease Progression
  • HIV-1 / genetics
  • HIV-1 / isolation & purification*
  • HIV-1 / pathogenicity*
  • Humans
  • RNA, Messenger / analysis
  • RNA, Viral / isolation & purification
  • Receptors, CCR3
  • Receptors, CCR5 / metabolism
  • Receptors, CCR8
  • Receptors, CXCR4 / genetics
  • Receptors, CXCR4 / metabolism
  • Receptors, Chemokine / metabolism*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sarcoma, Kaposi / metabolism*
  • Sarcoma, Kaposi / virology*
  • Tumor Cells, Cultured / metabolism
  • Tumor Cells, Cultured / virology

Substances

  • Actins
  • CCR3 protein, human
  • CCR8 protein, human
  • CD4 Antigens
  • DNA, Viral
  • RNA, Messenger
  • RNA, Viral
  • Receptors, CCR3
  • Receptors, CCR5
  • Receptors, CCR8
  • Receptors, CXCR4
  • Receptors, Chemokine