HIV-1 latently infected cells are recognized as the last barrier towards viral eradication and cure. To purge these latently infected cells, we developed an “activation-killing” approach by combining provirus stimulants (SAHA, prostratin or both) with a blocker of human CD59, a key member of regulators of complement activation (RCA), to facilitate anti-HIV-1 antibodies to trigger antibody-dependent complement-mediated lysis (ADCML) of latently-infected cells. We found that both SAHA and prostratin activated proviruses in ACH-2 cells, a well-characterized cellular model of HIV-1 latency, resulting in expression of HIV-1 gp120 on the cell surface. To prevent new rounds of infections by virus released from the stimulated cells, we treated ACH-2 cells with provirus stimulants plus antiretroviral drugs. We found that reverse transcription inhibitors had no effect on virion production, whereas protease inhibitors (PIs) significantly reduced the production of mature virions, but not gp120 expression on the cell surface. ACH-2 cells post-activation of provirus became sensitive to ADCML in the presence of a human CD59 blocker plus anti-HIV-1 gp120 antibodies or sera from HIV-1-infected patients. The lysis resulted from specific cell killing by anti-HIV-1 antibodies because the lysis did not occur using irrelevant antibodies or inactivated complement. Thus, a combination of provirus stimulants with RCA blockers represents a novel approach for purging HIV-1 latently infected cells.
- Copyright © 2013 by The American Association of Immunologists, Inc.