| Autor: |
Yang-Hui Jimmy Yeh, Kerui Yang, Anya Razmi, Ya-Chi Ho |
| Jazyk: |
angličtina |
| Rok vydání: |
2021 |
| Předmět: |
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| Zdroj: |
Viruses, Vol 13, Iss 9, p 1858 (2021) |
| Druh dokumentu: |
article |
| ISSN: |
1999-4915 |
| DOI: |
10.3390/v13091858 |
| Popis: |
More than 50% of the HIV-1 latent reservoir is maintained by clonal expansion. The clonally expanded HIV-1-infected cells can contribute to persistent nonsuppressible low-level viremia and viral rebound. HIV-1 integration site and proviral genome landscape profiling reveals the clonal expansion dynamics of HIV-1-infected cells. In individuals under long-term suppressive antiretroviral therapy (ART), HIV-1 integration sites are enriched in specific locations in certain cancer-related genes in the same orientation as the host transcription unit. Single-cell transcriptome analysis revealed that HIV-1 drives aberrant cancer-related gene expression through HIV-1-to-host RNA splicing. Furthermore, the HIV-1 promoter dominates over the host gene promoter and drives high levels of cancer-related gene expression. When HIV-1 integrates into cancer-related genes and causes gain of function of oncogenes or loss of function of tumor suppressor genes, HIV-1 insertional mutagenesis drives the proliferation of HIV-1-infected cells and may cause cancer in rare cases. HIV-1-driven aberrant cancer-related gene expression at the integration site can be suppressed by CRISPR-mediated inhibition of the HIV-1 promoter or by HIV-1 suppressing agents. Given that ART does not suppress HIV-1 promoter activity, therapeutic agents that suppress HIV-1 transcription and halt the clonal expansion of HIV-1-infected cells should be explored to block the clonal expansion of the HIV-1 latent reservoir. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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