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HTLV-1-encoded p30II is a post-transcriptional negative regulator of viral replication

Nature Medicine volume 10, pages 197–201 (2004)Cite this article

Abstract

Human T-cell leukemia/lymphoma virus type 1 (HTLV-1) persists despite a vigorous virus-specific host immune response, and causes adult T-cell leukemia and lymphoma in approximately 2% of infected individuals. Here we report that HTLV-1 has evolved a genetic function to restrict its own replication by a novel post-transcriptional mechanism. The HTLV-1-encoded p30II is a nuclear-resident protein that binds to, and retains in the nucleus, the doubly spliced mRNA encoding the Tax and Rex proteins. Because Tex and Rex are positive regulators of viral gene expression1,2, their inhibition by p30II reduces virion production. p30II inhibits virus expression by reducing Tax and Rex protein expression.

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Figure 1: Inhibition of HTLV-1 viral production by p30II.
Figure 2: p30II does not affect Tax protein expression, transcription or cellular localization.
Figure 3: p30II affects the nuclear-to-cytoplasmic export of Tax/Rex mRNA.
Figure 4: p30II binds to the Tax/Rex splice junction and inhibits virus expression in HTLV-1-infected cell lines.

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Acknowledgements

We thank S.J. Snodgrass for editorial assistance, B.K. Felber and G.N. Pavlakis for helpful discussion, and J. McNally and T. Karpova for advice on imaging.

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  1. Christophe Nicot

    Present address: Department of Microbiology, University of Kansas Medical Center, 3025 Wahl Hall West, Kansas City, Kansas, 66160, USA

Authors and Affiliations

  1. Animal Models and Retroviral Vaccines Section, National Cancer Institute, 41/D804, Bethesda, 20892, Maryland, USA

    Christophe Nicot, Julie M Johnson, Jake R Fullen, Norma Alonzo, Risaku Fukumoto & Genoveffa Franchini

  2. Laboratory of Receptor Biology and Gene Expression, National Cancer Institute, 41/D804, Bethesda, 20892, Maryland, USA

    Miroslav Dundr & Tom Misteli

  3. Basic Research Laboratory, Center for Cancer Research, National Cancer Institute at Frederick, Frederick, 21702-1201, Maryland, USA

    Gerald L Princler & David Derse

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Correspondence to Genoveffa Franchini.

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Nicot, C., Dundr, M., Johnson, J. et al. HTLV-1-encoded p30II is a post-transcriptional negative regulator of viral replication. Nat Med 10, 197–201 (2004). https://doi.org/10.1038/nm984

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