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

A. De Rossi, L. Ometto, S. Roncella, E. D'Andrea, C. Menin, F. Calderazzo, M. Rowe, M. Ferrarini, L. Chieco-Bianchi

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Abstract

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.

Original languageEnglish
Pages (from-to)234-244
Number of pages11
JournalVirology
Volume198
Issue number2
Publication statusPublished - 1994

ASJC Scopus subject areas

  • Virology
  • Infectious Diseases

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    De Rossi, A., Ometto, L., Roncella, S., D'Andrea, E., Menin, C., Calderazzo, F., Rowe, M., Ferrarini, M., & Chieco-Bianchi, L. (1994). 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. Virology, 198(2), 234-244.