Molecular mechanisms of poly [ADP-ribose] polymerase-1 in HIV-1 infection
Poly (ADP-ribose) polymerase-1 (PARP-1) is a cellular enzyme involved in genome stability and transcriptional regulation. The role of this protein in HIV-1 infection is largely controversial. Some reports indicated a fundamental role of PARP-1 in HIV-1 DNA integration and results from other laboratories do not support these conclusions. An important characteristic in all these experiments is that the HIV-1 target cells that were used express, in addition to PARP-1, the functional homologue PARP-2. We evaluated the role of PARP-1 in the chicken B lymphoblastoid cell line DT40. These cells naturally lack PARP-2 and support the early steps of HIV infection. We have observed that DT40 PARP-1 -/- cells was significantly more susceptible to infection with HIV- and murine leukemia virus (MLV)-derived viral vectors than their wild type counterpart. Expression of human PARP-1 in DT40 PARP-1 -/- cells decreased retroviral susceptibility to wild type levels, while expression of human PARP-2 has only a partial effect. Analysis of the retroviral life cycle by real time PCR indicated that levels of retroviral provirus were similar in DT40 wild type, PARP-1 -/-, and PARP-1 -/- cells expressing human PARP-1. These results, suggested that retroviral latency was established in cells expressing PARP-1. Treatment of HIV- or MLV-infected cells with the histone deacetylase inhibitor sodium butyrate or the DNA methyl transferase 1 inhibitor 5-azacytidine suppressed the differences in retroviral transgene expression observed in cells expressing or not PARP-1.
Reyes, Daniel, "Molecular mechanisms of poly [ADP-ribose] polymerase-1 in HIV-1 infection" (2011). ETD Collection for University of Texas, El Paso. AAI1503983.