DELAYED HUMAN-IMMUNODEFICIENCY-VIRUS TYPE 1-INDUCED APOPTOSIS IN CELLS EXPRESSING TRUNCATED FORMS OF CD4

It has been reported previously that cells expressing a truncated form of CD4 which lacks the cytoplasmic tail of the molecule (truncation a t position 402) were not sensitive to human immunodeficiency virus typ e 1 (HIV-1)-induced apoptosis in an acute-phase model of infection (J. Corbeil, M. Tremblay, and D. D. Richman, J. Exp. Med, 183:39-48, 1996 ). The role played by the cytoplasmic domain of CD4 in HIV-induced apo ptosis was reexamined here with clones of A2.01 cells expressing diffe rent farms of CD4 and the DNA intercalant YOPRO-1 assay, Six days afte r virus exposure, we found evidence of apoptosis in A2.01 cells expres sing the wild-type CD4 (A2.01/CD4), whereas enhanced apoptosis remaine d absent in cultures of A2.01/CD4.401 and A2.01/CD4.403 cells (A2.01 c ells which express CD4.401 and CD4.403 molecules with truncations at p ositions 401 and 403, respectively), However, cell death by apoptosis mensured with YOPRO-1 was found in cultures of A2.01/CD4.401 and A2.01 /CD4.403 cells 15 days after virus exposure. This result was confirmed with a terminal dUTP nick end-labeling assay and propidium iodide sta ining, The long lag time postinfection required for apoptosis to be ob served in cultures of infected cells expressing truncated forms of CD I was due to the delayed viral replication in these cells, as shown by monitoring of the viral reverse transcriptase activity and HIV-1 p24( gag) antigen expression. These results emphasize the relationship betw een virus replication and cell death by apoptosis.