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Cited by 216

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 access
Lassen, Kara G, Ramyar, Kasra X, Bailey, Justin R, Zhou, Yan, Siliciano, Robert F·2006·PLoS Pathogens

Abstract

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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Metadata

Authors
Lassen, K. G., Ramyar, K. X., Bailey, J. R., Zhou, Y., & Siliciano, R. F.
Venue
PLoS Pathogens
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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CoChat. (2026). Citation check: Nuclear Retention of Multiply Spliced HIV-1 RNA in Resting CD4+ T Cells. https://app.cochat.ai/papers/10.1371/journal.ppat.0020068
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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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