Studies on susceptibility of promonocytic cell line U937-derived subclones to HIV-1 infection and apoptosis induction

The promonocytic cell line U937, when infected with lymphotropic human immunodeficiency virus type 1 (HIV-1), becomes a continuous virus producer. A total of 46 subclones was isolated by limiting dilution of U937. These subclones were classified into three (2 high, 42 middle, and 2 low) types based on their susceptibility to HIV-1 infection, i.e., the appearance of viral antigens and following virus production. Analyses of cell surface antigens on representative 2 subclones in each type revealed that CD4 expression is similar level in all subclones, while LFA-1 expression is significantly lower than middle- and low-type subclones. After infection of HIV-1, different characteristics were observed among three types of subclones. First, superoxide was generated in the high-type subclones during all infection stages, even before HIV-1 replication, while in middle- and low-type subclones only transiently at acute phase of HIV-1 replication. Second, the cell differentiation was induced by HIV-1 infection only in high-type subclones, but not in low-type subclones. Thus, these results suggest that these subclones are different in the differentiation stage of the cell type. Analysis of the HIV-1 life cycles such as adsorption, reverse transcription, integration, transcription, and translation in the subclones, revealed that the different susceptibility is associated with the accumulation of unintegrated extra-chromosomal forms of HIV-1 DNA. In addition, the low-, but not high-type, subclones were sensitive for the apoptosis by treatment with TNF-alpha, anti-Fas antibody, or defective non-infectious HIV-1 particles. Thus, U937 could be devided into at least two populations, i.e., one for HIV-1 productive infection and the other for apoptosis without new HIV-1 replication, similarly as in the situation in infected HIV-1 carriers.