Chemokine Receptor CCR5 and CXCR4 Expression in HIV-Associated Kidney Disease

Abstract

The chemokine receptors CCR5 and CXCR4 have been identified as essential coreceptors for entry of HIV-1 strains into susceptible cells. Direct infection of renal parenchymal cells has been implicated in the pathogenesis of HIV-associated renal disease, although data are conflicting. The localization of CCR5 and CXCR4 in kidneys with HIV-associated renal disease is unknown. Formalin-fixed, paraffin-embedded renal biopsies from patients with HIV-associated nephropathy (HIVAN) (n = 13), HIV-associated immune complex glomerulonephritis (n = 3), HIV-associated thrombotic microangiopathy (n = 1), and HIV-negative patients with collapsing glomerulopathy (n = 8) were analyzed in this study. Cellular sites of expression of CCR5 and CXCR4 were identified by immunohistochemistry and by in situ hybridization. The presence of HIV-1 was detected by immunohistochemistry and by in situ hybridization. Expression of both chemokine receptors CCR5 and CXCR4 was undetectable in intrinsic glomerular, tubular, and renovascular cells in all analyzed cases. In the presence of tubulointerstitial inflammation, CCR5 and CXCR4 expression was localized to infiltrating mononuclear leukocytes. HIV-1 protein was undetectable by immunohistochemistry in all cases of HIV-associated renal disease. HIV-1 RNA was identified in one case of HIVAN but was restricted to infiltrating leukocytes. HIV-1 RNA was not detected in intrinsic renal cells in all analyzed cases. Identifying the cellular expression of HIV-coreceptors CCR5 and CXCR4 may help to clarify which tissues are permissive for direct HIV infection. These data do not support a role of productive HIV-1 infection of renal parenchymal cells in the pathogenesis of HIV-associated renal disease.