The DOI matches its Crossref record; 10 of the 10 references it cites were found in a registry or an index.
Nuclear Retention of Multiply Spliced HIV-1 RNA in Resting CD4+ T Cells
Open accessAbstract
HIV-1 latency in resting CD4+ T cells represents a major barrier to virus eradication in patients on highly active antiretroviral therapy (HAART). We describe here a novel post-transcriptional block in HIV-1 gene expression in resting CD4+ T cells from patients on HAART. This block involves the aberrant localization of multiply spliced (MS) HIV-1 RNAs encoding the critical positive regulators Tat and Rev. Although these RNAs had no previously described export defect, we show that they exhibit strict nuclear localization in resting CD4+ T cells from patients on HAART. Overexpression of the transcriptional activator Tat from non-HIV vectors allowed virus production in these cells. Thus, the nuclear retention of MS HIV-1 RNA interrupts a positive feedback loop and contributes to the non-productive nature of infection of resting CD4+ T cells. To define the mechanism of nuclear retention, proteomic analysis was used to identify proteins that bind MS HIV-1 RNA. Polypyrimidine tract binding protein (PTB) was identified as an HIV-1 RNA-binding protein differentially expressed in resting and activated CD4+ T cells. Overexpression of PTB in resting CD4+ T cells from patients on HAART allowed cytoplasmic accumulation of HIV-1 RNAs. PTB overexpression also induced virus production by resting CD4+ T cells. Virus culture experiments showed that overexpression of PTB in resting CD4+ T cells from patients on HAART allowed release of replication-competent virus, while preserving a resting cellular phenotype. Whether through effects on RNA export or another mechanism, the ability of PTB to reverse latency without inducing cellular activation is a result with therapeutic implications.
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Cites
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“spliced viral HIV-1 RNAs to the cytoplasm [56–59].”
BackgroundRegulation of alternative splicing by PTB and associated factors
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Cited by
The Challenge of Finding a Cure for HIV Infection
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Cellular microRNAs contribute to HIV-1 latency in resting primary CD4+ T lymphocytes
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HIV rebounds from latently infected cells, rather than from continuing low-level replication
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Metadata
- Authors
- Lassen, K. G., Ramyar, K. X., Bailey, J. R., Zhou, Y., & Siliciano, R. F.
- Venue
- PLoS Pathogens
- Publisher
- Public Library of Science (PLoS)
- Published
- 2006-07-07
- Volume
- 2
- Issue
- 7
- Pages
- e68
- ISSN
- 1553-7366 (ISSN-L)
- 1553-7374
- OpenAlex
- W1996808619
- Cited by
- 216
- References
- 10
- FWCI
- 4.34
- Type
- journal article
- Language
- en
- Open access
- gold
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- Lassen, K. G., Ramyar, K. X., Bailey, J. R., Zhou, Y., & Siliciano, R. F. (2006). Nuclear Retention of Multiply Spliced HIV-1 RNA in Resting CD4+ T Cells. PLoS Pathogens. https://doi.org/10.1371/journal.ppat.0020068
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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