Microglia in the giant cell encephalitis of acquired immune deficiency syndrome: proliferation, infection and fusion

Abstract

The autopsied brains of three homosexual men with acquired immune deficiency syndrome (AIDS), progressive encephalopathy and widespread multinucleated giant cell encephalitis were investigated by lectin and immunohistochemical methods to ascertain the cellular distribution of a human immunodeficiency virus (HIV) core protein, p25. Abundant viral antigen was present in all brains, limited to perivascular macrophages, microglial and multinucleated cells, some bearing elongated cytoplasmic processes. The multinucleated cells were consistently labelled by the lectin Ricinus communis agglutinin-1, a marker for microglia, which demonstrated process-bearing variants of these cells. The prominent staining of microglia for viral antigen and the morphological suggestion that they fuse with other microglia and/or macrophages to form the multinucleated cells characteristic of HIV encephalitis indicate that microglia are probably direct targets of HIV infection and serve to propagate and amplify this retroviral encephalitis.

SIV infection of macaques - modeling the progression to AIDS dementia

“…Productive replication of HIV in the brain occurs mainly in cells of macrophage lineage. Viral antigen and RNA are regularly identi®ed in perivascular and meningeal macrophages and in microglial cells within the brain parenchyma, suggesting that the ability of HIV to replicate in monocytes/macrophages is a prerequisite for infection in the brain and viral neurovirulence (Koenig et al, 1986;Michaels et al, 1988;Price et al, 1988). Studies of the molecular determinants for neurovirulence of HIV strains are, however, limited by the fact that few primary HIV isolates from the brain have been studied, and brain isolates are frequently cultured extensively in vitro, often in cell lines.…”

The invasive and destructive behavior of HIV-induced T cell syncytia on collagen and endothelium

“…It seems reasonable to suggest that the incapacity of syncytia to translocate on hydrated collagen is due to pseudopodial invasion of the gel. Long cytoplasmic processes have also been found emanating from multinucleated giant cells in autopsies of three AIDS patients who had suffered from encephalitis [30], demonstrating that syncytia can form these processes in vivo.…”

“…T cells infected with HIV can form large, multinucleated syncytia in vitro [2][3][4][5] and recent studies in vivo have demonstrated that in addition to the central nervous system [e.g., see refs. [28][29][30], such syncytia can be found in adenoid and tonsillar tissue [6,7] If syncytia can form in vivo, and if they can be motile, how would they behave in tissue stroma and at the walls of blood vessels? To begin to answer this question, we have compared the morphology and behavior of individual SUP-T1 cells and HIV-induced T cell syncytia incubated on dehydrated and hydrated collagen gels, and on a vessel wall model of BAE grown to confluency on hydrated collagen.…”

Microglial Cells in the Central Nervous System of the Rabbit and Rat: Cytochemical Identification Using Two Different Lectins

“…Heretofore, lectin histochemistry has been scarcely used to investigate the origin of the microglial cells [ 14,15] or the reactions of this cell type to different insults, both in experimental [16] and human pathology [17][18][19]. In our opinion, lectin histochemistry provides sound advantages for the study of the microglia.…”