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Kuo Chen-Yen Ku Cheng-Lung Lim Hye-Kyung Hsia Shao-Hsuan Lin Jainn-Jim Lo Chia-Chi Ding Jing-Ya Kuo Rei-Lin Casanova Jean-Laurent Zhang Shen-Ying Chang Luan-Yin Lin Tzou-Yien 《Journal of clinical immunology》2022,42(3):606-617
Journal of Clinical Immunology - Enterovirus A71 (EV71) causes a broad spectrum of childhood diseases, ranging from asymptomatic infection or self-limited hand-foot-and-mouth disease (HFMD) to... 相似文献
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Das K Ma LC Xiao R Radvansky B Aramini J Zhao L Marklund J Kuo RL Twu KY Arnold E Krug RM Montelione GT 《Proceedings of the National Academy of Sciences of the United States of America》2008,105(35):13093-13098
Influenza A viruses are responsible for seasonal epidemics and high mortality pandemics. A major function of the viral NS1A protein, a virulence factor, is the inhibition of the production of IFN-β mRNA and other antiviral mRNAs. The NS1A protein of the human influenza A/Udorn/72 (Ud) virus inhibits the production of these antiviral mRNAs by binding the cellular 30-kDa subunit of the cleavage and polyadenylation specificity factor (CPSF30), which is required for the 3′ end processing of all cellular pre-mRNAs. Here we report the 1.95-Å resolution X-ray crystal structure of the complex formed between the second and third zinc finger domain (F2F3) of CPSF30 and the C-terminal domain of the Ud NS1A protein. The complex is a tetramer, in which each of two F2F3 molecules wraps around two NS1A effector domains that interact with each other head-to-head. This structure identifies a CPSF30 binding pocket on NS1A comprised of amino acid residues that are highly conserved among human influenza A viruses. Single amino acid changes within this binding pocket eliminate CPSF30 binding, and a recombinant Ud virus expressing an NS1A protein with such a substitution is attenuated and does not inhibit IFN-β pre-mRNA processing. This binding pocket is a potential target for antiviral drug development. The crystal structure also reveals that two amino acids outside of this pocket, F103 and M106, which are highly conserved (>99%) among influenza A viruses isolated from humans, participate in key hydrophobic interactions with F2F3 that stabilize the complex. 相似文献
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Chen Zhao Tien-Ying Hsiang Rei-Lin Kuo Robert M. Krug 《Proceedings of the National Academy of Sciences of the United States of America》2010,107(5):2253-2258
ISG15 is an IFN-α/β–induced, ubiquitin-like protein that is conjugated to a wide array of cellular proteins through the sequential action of three conjugation enzymes that are also induced by IFN-α/β. Recent studies showed that ISG15 and/or its conjugates play an important role in protecting cells from infection by several viruses, including influenza A virus. However, the mechanism by which ISG15 modification exerts antiviral activity has not been established. Here we extend the repertoire of ISG15 targets to a viral protein by demonstrating that the NS1 protein of influenza A virus (NS1A protein), an essential, multifunctional protein, is ISG15 modified in virus-infected cells. We demonstrate that the major ISG15 acceptor site in the NS1A protein in infected cells is a critical lysine residue (K41) in the N-terminal RNA-binding domain (RBD). ISG15 modification of K41 disrupts the association of the NS1A RBD domain with importin-α, the protein that mediates nuclear import of the NS1A protein, whereas the RBD retains its double-stranded RNA-binding activity. Most significantly, we show that ISG15 modification of K41 inhibits influenza A virus replication and thus contributes to the antiviral action of IFN-β. We also show that the NS1A protein directly and specifically binds to Herc5, the major E3 ligase for ISG15 conjugation in human cells. These results establish a “loss of function” mechanism for the antiviral activity of the IFN-induced ISG15 conjugation system, namely, that it inhibits viral replication by conjugating ISG15 to a specific viral protein, thereby inhibiting its function. 相似文献
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Serotype-specific detection of enterovirus 71 in clinical specimens by DNA microchip array 总被引:6,自引:0,他引:6
Shih SR Wang YW Chen GW Chang LY Lin TY Tseng MC Chiang C Tsao KC Huang CG Shio MR Tai JH Wang SH Kuo RL Liu WT 《Journal of virological methods》2003,111(1):55-60
Enterovirus 71 is an important pathogen that causes high morbidity and mortality in children in Taiwan. Virus isolation in cell cultures has been the standard method for enterovirus 71 identification in Clinical Virology Laboratories. However, virus isolation takes 5-10 days when using cell culture. A microchip for enterovirus 71 detection was developed as an alternative diagnostic method. The novel approach is based on hybridization of amplified DNA specimens with oligonucleotide DNA probes immobilized on a microchip. Two oligonucleotides were used as detection probes, the pan-enterovirus sequence located in the 5'-noncoding region (5'-NCR) and the enterovirus 71-specific sequence located in the VP2 region. The diagnostic procedure takes 6 h. One hundred specimens identified as enteroviruses by viral cultures were tested using this microchip, including 67 enterovirus 71 specimens. The sensitivity of the novel method is 89.6% and its specificity is 90.9%. The enterovirus 71-microchip can detect the amplicon derived from viral RNA corresponding to 1-10 virions in a clinical specimen. Microchip array is a potential diagnostic method for identification of enterovirus in the future. 相似文献
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