Skills (2)
Publications (18) View all
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Article: A PY-nuclear localization signal is required for nuclear accumulation of HCMV UL79 protein.
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ABSTRACT: Human cytomegalovirus UL79 protein is recently reported to be required for transcription or efficient accumulation of late viral mRNAs during viral infection. An absolute nuclear distribution of UL79 proteins has been observed with immunofluorescence assay, both during the infection of Flag-tagged UL79 recombinant virus and in the HFFs expressing HA-tagged UL79, with or without virus infection. However, little is known about the nuclear import mechanism of UL79 protein. Here, by utilizing living cells fluorescent microscopy, a predominant nuclear localization of UL79 protein in living cells was detected. Furthermore, the nuclear import of UL79 protein was demonstrated to be dependent on the transportin-1-mediated pathway. Finally, a hydrophobic PY-nuclear localization signal (PY-NLS) was delineated between the amino acids 66-92 of UL79 protein. Collectively, we provide evidence that a PY-NLS, firstly described in viral proteins, is responsible for the nuclear accumulation of UL79 protein.Medical Microbiology and Immunology 05/2012; 201(3):381-7. · 3.83 Impact Factor -
Article: Identification of a novel NLS of herpes simplex virus type 1 (HSV-1) VP19C and its nuclear localization is required for efficient production of HSV-1.
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ABSTRACT: Herpes simplex virus type 1 (HSV-1) triplex is a complex of three protein subunits, consisting of two copies of VP23 and one copy of VP19C. Here, we identified a non-classical NLS of VP19C between aa 50 and 61, and the nuclear import of VP19C was mediated by RanGTP and importin β1-, but not importin α5-, dependent pathway. Additionally, recombinant virus harbouring this NLS mutation (NLSm) replicates less efficiently as wild-type. These data strongly suggested that the nuclear import of VP19C is required for efficient HSV-1 production.Journal of General Virology 05/2012; 93(Pt 9):1869-75. · 3.36 Impact Factor -
Article: Live cell imaging fails to support viral-protein-mediated intercellular trafficking.
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ABSTRACT: The herpes simplex virus type I protein VP22 has been reported to have the property of intercellular trafficking. However, there is little direct evidence to demonstrate that VP22 can shuttle freely between living cells. Here, we employ a novel and simple assay using live cell fluorescence microscopy to investigate the intercellular transport property. Our results demonstrated that VP22, bovine herpesvirus-1 VP22, HSV-1 US11 and HIV Tat could not shuttle into neighboring cells via direct contact.Archives of Virology 04/2012; 157(7):1383-6. · 2.11 Impact Factor -
Article: Characterization of nuclear import and export signals determining the subcellular localization of WD repeat-containing protein 42A (WDR42A).
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ABSTRACT: WD repeat-containing protein 42A (WDR42A) is a member of the WD40-repeat proteins. Here, we investigated the localization pattern of WDR42A in living cells. By mutational analysis, a nuclear localization signal, 114PRRRVQRKR122, was for the first time determined. The dominant negative, co-immunoprecipitation and GST pull-down results further demonstrated that the nuclear import of WDR42A was mediated by karyopherin-α1/β1 in conjunction with the GTPase Ran. Additionally, a nuclear export signal, 39IEVEASDLSLSL50, was verified to be a functional NES, which mediated the nuclear export through Chromosome Region Maintenance 1 dependent pathway. All these data suggest WDR42A is a nucleocytoplasmic shuttling protein.FEBS letters 03/2012; 586(8):1079-85. · 3.54 Impact Factor -
Article: Herpes simplex virus 1 tegument protein US11 downmodulates the RLR signaling pathway via direct interaction with RIG-I and MDA-5.
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ABSTRACT: The interferon (IFN)-mediated antiviral response is a major defense of the host immune system. In order to complete their life cycle, viruses must modulate host IFN-mediated immune responses. Herpes simplex virus 1 (HSV-1) is a large DNA virus containing more than 80 genes, many of which encode proteins that are involved in virus-host interactions and show immune modulatory capabilities. In this study, we demonstrate that the US11 protein, an RNA binding tegument protein of HSV-1, is a novel antagonist of the beta IFN (IFN-β) pathway. US11 significantly inhibited Sendai virus (SeV)-induced IFN-β production, and its double-stranded RNA (dsRNA) binding domain was indispensable for this inhibition activity. Additionally, wild-type HSV-1 coinfection showed stronger inhibition than US11 mutant HSV-1 in SeV-induced IFN-β production. Coimmunoprecipitation analysis demonstrated that the US11 protein in HSV-1-infected cells interacts with endogenous RIG-I and MDA-5 through its C-terminal RNA-binding domain, which was RNA independent. Expression of US11 in both transfected and HSV-1-infected cells interferes with the interaction between MAVS and RIG-I or MDA-5. Finally, US11 dampens SeV-mediated IRF3 activation. Taken together, the combined data indicate that HSV-1 US11 binds to RIG-I and MDA-5 and inhibits their downstream signaling pathway, preventing the production of IFN-β, which may contribute to the pathogenesis of HSV-1 infection.Journal of Virology 02/2012; 86(7):3528-40. · 5.40 Impact Factor
