HIV-1 induces down-regulation of bcl-2 expression and death by apoptosis of EBV-immortalized B cells: a model for a persistent "self-limiting" HIV-1 infection.
Interactions between HIV-1 and EBV were studied in HIV-1-infected EBV-positive lymphoblastoid B cells. Following in vitro exposure of B cells to HIV-1, the number of infected cells reached a plateau (25-35%) in approximately 20 days and remained fairly stable thereafter, despite the presence of infectious virus in culture supernatants. HIV-1-positive (gp120+) were separated from HIV-1-negative (gp120-) cells, and the two fractions were further characterized for EBV antigens, bcl-2 expression, and growth capacity in vitro. Compared to gp120- cells, EBNA 1, EBNA 2, and LMP 1 were down-regulated, and the episomal form of EBV-DNA was dramatically decreased in the gp120+ cells. When plated in culture gp120+, but not gp120-, cells died; BZLF1 antigen was not expressed, thus ruling out a reactivation of the EBV lytic cycle. Cytofluorometric, morphological, and molecular analyses disclosed that gp120+ cell death was due instead to apoptosis; evidence of bcl-2 down-regulation in these cells was consistent with this finding. gp120+ cell apoptosis contributed to keeping the level of HIV-1-infected cells at a steady state in the unfractionated culture, where persistent infection was maintained by HIV-1 transmission to B cells newly arising from the proliferation of HIV-1-uninfected cells.
De Rossi
A
A
Institute of Oncology, University of Padova, Padua, Italy.
Ometto
L
L
Roncella
S
S
D'Andrea
E
E
Menin
C
C
Calderazzo
F
F
Rowe
M
M
Ferrarini
M
M
Chieco-Bianchi
L
L
D000163:Acquired Immunodeficiency Syndrome / Q000382:microbiology*; D017209:Apoptosis; D001402:B-Lymphocytes / Q000382:microbiology*; D002461:Cell Line, Transformed; D015536:Down-Regulation; D015497:HIV-1 / Q000254:growth & development / Q000378:metabolism*; D004854:Herpesvirus 4, Human / Q000235:genetics; D006801:Humans; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D019253:Proto-Oncogene Proteins c-bcl-2; D014775:Virus Activation
D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2