Infection of mesangial cells with HIV and SIV: identification of GPR1 as a coreceptor

Kidney Int. 2000 Aug;58(2):607-17. doi: 10.1046/j.1523-1755.2000.00207.x.


Background: Mesangial cells are an important component of the glomerulus. Dysfunction of mesangial cells is thought to be involved in the development of human immunodeficiency virus type 1 (HIV-1)-associated nephropathy (HIVAN). HIVAN is a structural renal failure frequently observed in patients with acquired immune deficiency syndrome. However, the susceptibility of mesangial cells to HIV-1 is disputable. More than ten G protein-coupled receptors, including chemokine receptors, have been shown to act as HIV-1 coreceptors that determine the susceptibilities of cells to HIV-1 strains with specific cell tropisms.

Methods: We examined the susceptibility of mesangial cells to various HIV-1, HIV type 2 (HIV-2) and simian immunodeficiency virus (SIV) strains. Expression of CD4 and HIV/SIV coreceptors was examined by Western blotting and polymerase chain reaction.

Results: Mesangial cells were found to be susceptible to HIV-1 variant and mutants that infect brain-derived cells, but highly resistant to T-tropic (X4), M-tropic (R5) or dual-tropic (X4R5) HIV-1 strains. In addition, mesangial cells were also susceptible to HIV-2 and SIV strains that infect the brain-derived cells. Among HIV/SIV coreceptors we tested, the expression of GPR1 mRNA was detected in mesangial cells. Expression of CD4 mRNA and protein was also detected in them. Mesangial cells and GPR1-transduced CD4-positive cells showed similar susceptibilities to the HIV-1 variant and mutants and HIV-2 and SIV strains.

Conclusions: CD4 and GPR1 mRNAs were detected in mesangial cells. Mesangial cells were susceptible to HIV/SIV strains that use GPR1 as a coreceptor. Our findings suggest that an orphan G protein-coupled receptor, GPR1, is a coreceptor expressed in mesangial cells. It remains to be investigated whether the interaction of mesangial cells with specific HIV-1 strains through GPR1 plays a role in the development of HIVAN.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • AIDS-Associated Nephropathy / physiopathology
  • AIDS-Associated Nephropathy / virology*
  • Apoptosis
  • CD4 Antigens / analysis
  • CD4 Antigens / genetics
  • Cells, Cultured
  • Disease Susceptibility
  • Fibroblasts / chemistry
  • Fibroblasts / cytology
  • Fibroblasts / physiology
  • Gene Expression Regulation, Viral
  • Glomerular Mesangium / cytology
  • Glomerular Mesangium / virology*
  • HIV Envelope Protein gp120 / genetics
  • HIV-1 / genetics
  • HIV-1 / pathogenicity*
  • HIV-2 / pathogenicity*
  • Humans
  • Mutation
  • Peptide Fragments / genetics
  • RNA, Messenger / analysis
  • Receptors, Cell Surface / analysis
  • Receptors, Cell Surface / genetics*
  • Receptors, G-Protein-Coupled*
  • Saccharomyces cerevisiae Proteins*
  • Simian Immunodeficiency Virus / pathogenicity*
  • Skin / cytology
  • Virulence


  • CD4 Antigens
  • GPR1 protein, S cerevisiae
  • HIV Envelope Protein gp120
  • HIV envelope protein gp120 (305-321)
  • Peptide Fragments
  • RNA, Messenger
  • Receptors, Cell Surface
  • Receptors, G-Protein-Coupled
  • Saccharomyces cerevisiae Proteins