Infection of mesangial cells with HIV and SIV: identification of GPR1 as a coreceptor.
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.
Tokizawa
S
S
Department of Virology and Preventive Medicine, Gunma University School of Medicine, Japan.
Shimizu
N
N
Hui-Yu
L
L
Deyu
F
F
Haraguchi
Y
Y
Oite
T
T
Hoshino
H
H
D016263:AIDS-Associated Nephropathy / Q000503:physiopathology / Q000821:virology*; D017209:Apoptosis; D015704:CD4 Antigens / Q000032:analysis / Q000235:genetics; D002478:Cells, Cultured; D004198:Disease Susceptibility; D005347:Fibroblasts / Q000737:chemistry / Q000166:cytology / Q000502:physiology; D015967:Gene Expression Regulation, Viral; D005920:Glomerular Mesangium / Q000166:cytology / Q000821:virology*; D015699:HIV Envelope Protein gp120 / Q000235:genetics; D015497:HIV-1 / Q000235:genetics / Q000472:pathogenicity*; D015498:HIV-2 / Q000472:pathogenicity*; D006801:Humans; D009154:Mutation; D010446:Peptide Fragments / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D011956:Receptors, Cell Surface / Q000032:analysis / Q000235:genetics*; D043562:Receptors, G-Protein-Coupled; D029701:Saccharomyces cerevisiae Proteins; D015302:Simian Immunodeficiency Virus / Q000472:pathogenicity*; D012867:Skin / Q000166:cytology; D014774:Virulence
D015704:CD4 Antigens; C109334:GPR1 protein, S cerevisiae; D015699:HIV Envelope Protein gp120; C059762:HIV envelope protein gp120 (305-321); D010446:Peptide Fragments; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D029701:Saccharomyces cerevisiae Proteins