Mutual interactions between HIV-1 and the host cell cycle: Implications for the neuropathogenesis of ADC
Progression of host cells through the mitotic division cycle provides a changing environment that can influence replication of the human immunodeficiency virus type-1 (HIV-1). There is increasing evidence that the position of the cell in the cell cycle regulates several steps in the viral life cycle, including reverse transcription of HIV-1 RNA and nuclear translocation of the viral pre-integration complex. In the following manuscripts, we provide evidence that HIV-1 transcription is also linked to the host cell cycle. E2F-1 is a transcriptional activator that is involved in promoting entry of cells into the S-phase. Our studies demonstrate that this protein represses HIV-1 transcription by binding to a site within the NF-kB enhancer region of the HIV-1 LTR and interacting with the 50kDa DNA-binding subunit of NF-kB. The retinoblastoma protein is involved in inhibiting cell cycle progression, at least in part through its ability to interact with E2F-1. Rb, in its underphosphorylated form, enhances NF-kB mediated transcription. Since this form of Rb also interacts with E2F-1, it is likely that Rb may function by inhibiting the negative effects of E2F-1 on the HIV-1 promoter. Our data suggests that cells early in the G1 phase contain an array of factors which promote high levels of HIV-1 transcription. ^ In addition to examining the effects of host cell cycle progression of the HIV-1 transcription, we investigated the effect of the HIV-1 Tat protein on cell proliferation. Our studies demonstrate that Tat arrests astrocytic cells in the G1 phase. This arrest is associated with the dysregulated G1 kinase activity and inhibition of Rb phosphorylation. We propose that the mutual interactions between virus and host, with respect to cell proliferation and viral replication, may establish a positive feed-back loop that may contribute to the pathogenesis of AIDS. ^
Biology, Molecular|Biology, Cell|Biology, Microbiology
"Mutual interactions between HIV-1 and the host cell cycle: Implications for the neuropathogenesis of ADC"
(January 1, 1999).
ETD Collection for Thomas Jefferson University.