Abstract
Qualitative differences among strains of Human Immunodeficiency Virus type 1 (HIV-1) may influence viral infectivity for cells of the central nervous system (CNS) and determine or at least significantly influence the neuropathogenesis of brain infection. In this study, we compared infectivity for these cells in vitro among several different laboratory-adapted HIV-1 strains differing in cellular tropism. These strains included three lymphotropic strains (SF2, NL4-3, and SG3.1), two macrophage-tropic strains (SF128A, SF162), and one brain-derived strain (YU2). In microglia, macrophage-tropic strain SF128A established productive infection while the lymphotropic strain SF2 did not. In infected astrocytes, all HIV-1 strains transiently produced variable and much lower levels of p24 antigen. Viral DNA env or tat gene sequences were amplified from infected astrocytes; the amplified signals varied among HIV-1 strains, but the strongest viral DNA signals were obtained from cells infected by the lymphotropic strains SF2 and SG3.1. Transfection of astrocytes with infectious HIV-1 proviral DNA clones confirmed the observation that HIV-1 strains differ in their ability to replicate in astrocytes. Transfection revealed post-entry blocks to replication by macrophage-tropic proviruses pSFl28A and pSF162. However, cytomegalovirus (CMV) superinfection of transfected astrocytes enhanced p24 production by lymphotropic HIV-1 proviruses twofold and stimulated p24 production by the otherwise inactive macrophage-tropic proviruses. This study demonstrates the spectrum of HIV-1 strain-associated variation in infectivity for neuroglia, and suggests, in addition, that herpesviral factors or viral-induced cellular factors may stimulate HIV-1 infection in astrocytes and expand the neural cell tropism of certain HIV-1 strains.
