Infection of mesangial cells with HIV and SIV: Identification of GPR1 as acoreceptor

Background. Mesangial cells are an important component of the glomerulus. D ysfunction of mesangial cells is thought to be involved in the development of human immunodeficiency virus type 1 (HIV-1)-associated nephropathy (HIVA N). HIVAN is a structural renal failure frequently observed in patients wit h acquired immune deficiency syndrome. However, the susceptibility of mesan gial cells to HIV-1 is disputable. More than ten G protein-coupled receptor s, including chemokine receptors, have been shown to act as HIV-1 corecepto rs that determine the susceptibilities of cells to HIV-1 strains with speci fic 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. Expre ssion of CD4 and HIV/SIV coreceptors was examined by Western blotting and p olymerase 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, mesang ial cells were also susceptible to HIV-2 and SIV strains that infect the br ain-derived cells. Among HIV/SIV coreceptors we tested, the expression of G PR1 mRNA was detected in mesangial cells. Expression of CD4 mRNA and protei n was also detected in them. Mesangial cells and GPR1-transduced CD4-positi ve cells showed similar susceptibilities to the HIV-1 variant and mutants a nd 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. O ur findings suggest that an orphan G protein-coupled receptor, GPR1, is a c oreceptor expressed in mesangial cells. It remains to be investigated wheth er the interaction of mesangial cells with specific HIV-1 strains through G PR1 plays a role in the development of HIVAN.