SEQUENCES REGULATING TROPISM OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 FOR BRAIN CAPILLARY ENDOTHELIAL-CELLS MAP TO A UNIQUE REGION ON THE VIRAL GENOME

Two infectious molecular clones of human immunodeficiency virus type 1 , NL4-3 and JR-CSF, differ in their abilities to productively infect h uman brain capillary endothelial (HBCE) cells. The phenotypes of recom binants between these two molecular strains were examined to identify viral sequences responsible for the difference in HBCE cell tropism be tween the two parental strains. Our results indicate that HBCE cell tr opism maps to a region that encompasses the C1 region of env and inclu des overlapping reading frames for the accessory genes vpr, vpu, tat, and rev. This region was unique for HBCE cell tropism and did not cose gregate with either macrophage or T-cell line tropism. However, severa l recombinant clones displayed dual tropism for both HBCE cells and ma crophages. These endothelial cell- and macrophage-tropic strains may h ave a unique pathogenic advantage by entering the brain via HBCE cells and subsequently infecting microglial cells with high efficiency, lea ding to the induction of human immunodeficiency virus dementia.