MORPHOLOGICAL-DIFFERENTIATION OF HUMAN SH-SY5Y NEUROBLASTOMA-CELLS INHIBITS HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 INFECTION

We have studied human immunodeficiency virus type 1 (HIV-1) infection in human SH-SY5Y neuroblastoma cells at various stages of morphologica l differentiation. Two days' treatment of the cells with retinoic acid (RA) or dibutyryl cAMP (db-cAMP) resulted in the appearance of elonga ted neurites and enhanced production of 160K to 200K neurofilament pro teins as shown by indirect immunofluorescence. DNA synthesis was reduc ed only in RA-treated cells as detected by 5-bromo-2'-deoxyuridine inc orporation. The cells were infected with two T-lymphotropic virus stra ins (IIIB and NDK) and two fresh isolates (39001 and 46001) from bronc hoalveolar lavage samples of AIDS patients. The latter two isolates we re unable to form syncytia in infected CD4-positive T-lymphoblastoid C 8166 cells which was in contrast to our T-lymphotropic virus strains. Interphase in situ hybridization showed that 14 to 16 % of SH-SY5Y cel ls become positive for HIV-1 DNA. Regardless of the virus strain, morp hological differentiation of the cells with RA or db-cAMP inhibited in fection by 50 % at a single cell in situ resolution. Nested PCR confir med the presence of proviral DNA in the infected cells. These results show that human neuroblastoma cells, tumour cells of neuroectodermal o rigin, can be infected by different HIV-I isolates and that the infect ion is inhibited by neurotypic cell differentiation.