Thrombotic microangiopathy in the HIV-2-infected macaque

Thrombotic microangiopathy (TMA) has been increasingly reported in human im munodeficiency virus (HIV)-infected humans over the past decade, The pathog enesis is unknown, We prospectively analyzed the rectal pathology and funct ion of 27 pigtailed macaques (Macaca nemestrina), infected intravenously wi th a virulent HIV-2 strain, HIV-2(287), in addition to that of four uninfec ted control macaques, Necropsies were performed between 12 hours and 28 day s after infection. HIV-2 antigen was detectable in peripheral blood mononuc lear cell (PBMC) cocultures in all animals after 10 days of HIV-2 infection ; a rapid decline in CD4(+) PBMC (<350/mu l) was seen in five of six animal s 21 days and 28 days after infection, No macaque developed features of cli nical AIDS, Typical lesions of human HIV-associated nephropathy were undete ctable. Six of the 27 HIV-2-infected macaques demonstrated both histologica l TMA lesions (thrombi in glomerular capillary loops and small arteries, me sangiolysis) and ultrastructural lesions (mesangiolysis, subendothelial luc ency, platelet thrombi in glomerular capillary lumina). Extrarenal thrombi were detected in the gastrointestinal and adrenal microvasculature of macaq ues that had developed renal TMA, None of the control animals demonstrated features of renal TMA at necropsy, In a retrospective analysis of kidneys o btained from 39 additional macaques infected with HIV-2(287), seven cases d emonstrated TMA. In situ hybridization showed no detectable HIV-2 RNA in ki dney sections of 65/66 HIV-2-infected macaques, including all 13 TMA cases. Expression of the chemokine receptor CXCR4, the putative coreceptor for HI V-2-2(287), was absent in intrinsic renal cells in all HIV-2-infected macaq ues, The HIV-2-infected macaque may be a useful. model of human HIV-associa ted TMA. Our data do not support a role of direct HIV-2 infection of intrin sic renal cells as an underlying mechanism.