1. A functional screen identifies transcriptional networks that regulate HIV-1 and HIV-2.
- Author
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Pedro KD, Agosto LM, Sewell JA, Eberenz KA, He X, Fuxman Bass JI, and Henderson AJ
- Subjects
- CD4-Positive T-Lymphocytes metabolism, Gene Expression Regulation, Viral, Gene Regulatory Networks, HIV Infections genetics, HIV Infections virology, HIV-1 genetics, HIV-2 genetics, Host-Pathogen Interactions, Humans, Protein Binding, Transcription Factors genetics, Transcription, Genetic, Viral Proteins genetics, HIV Infections metabolism, HIV-1 metabolism, HIV-2 metabolism, Transcription Factors metabolism, Viral Proteins metabolism
- Abstract
The molecular networks involved in the regulation of HIV replication, transcription, and latency remain incompletely defined. To expand our understanding of these networks, we performed an unbiased high-throughput yeast one-hybrid screen, which identified 42 human transcription factors and 85 total protein-DNA interactions with HIV-1 and HIV-2 long terminal repeats. We investigated a subset of these transcription factors for transcriptional activity in cell-based models of infection. KLF2 and KLF3 repressed HIV-1 and HIV-2 transcription in CD4+ T cells, whereas PLAGL1 activated transcription of HIV-2 through direct protein-DNA interactions. Using computational modeling with interacting proteins, we leveraged the results from our screen to identify putative pathways that define intrinsic transcriptional networks. Overall, we used a high-throughput functional screen, computational modeling, and biochemical assays to identify and confirm several candidate transcription factors and biochemical processes that influence HIV-1 and HIV-2 transcription and latency., Competing Interests: The authors declare no competing interest.
- Published
- 2021
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