37 results on '"Dong, Yan"'
Search Results
2. Suppression of JAK-STAT Signaling by Epstein-Barr Virus Tegument Protein BGLF2 through Recruitment of SHP1 Phosphatase and Promotion of STAT2 Degradation
- Author
-
Wai-Yin Lui, Kit-San Yuen, Michael G. Botelho, Vidyanath Chaudhary, Aradhana Bharti, Sonia Jangra, and Dong-Yan Jin
- Subjects
Epstein-Barr Virus Infections ,Herpesvirus 4, Human ,MAP Kinase Signaling System ,Immunology ,Virus Replication ,medicine.disease_cause ,Recombinant virus ,Microbiology ,03 medical and health sciences ,Interferon ,Virology ,medicine ,STAT1 ,Phosphorylation ,STAT2 ,030304 developmental biology ,0303 health sciences ,biology ,Protein Tyrosine Phosphatase, Non-Receptor Type 6 ,030302 biochemistry & molecular biology ,STAT2 Transcription Factor ,Epstein–Barr virus ,Virus-Cell Interactions ,Ubiquitin ligase ,Cell biology ,STAT1 Transcription Factor ,Lytic cycle ,Insect Science ,Host-Pathogen Interactions ,biology.protein ,Interferons ,Viral Fusion Proteins ,Oncovirus ,Signal Transduction ,medicine.drug - Abstract
Some lytic proteins encoded by Epstein-Barr virus (EBV) suppress host interferon (IFN) signaling to facilitate viral replication. In this study, we sought to identify and characterize EBV proteins antagonizing IFN signaling. The induction of IFN-stimulated genes (ISGs) by IFN-β was effectively suppressed by EBV. A functional screen was therefore performed to identify IFN-antagonizing proteins encoded by EBV. EBV tegument protein BGLF2 was identified as a potent suppressor of JAK-STAT signaling. This activity was found to be independent of its stimulatory effect on p38 and JNK pathways. Association of BGLF2 with STAT2 resulted in more pronounced K48-linked polyubiquitination and proteasomal degradation of the latter. Mechanistically, BGLF2 promoted the recruitment of SHP1 phosphatase to STAT1 to inhibit its tyrosine phosphorylation. In addition, BGLF2 associated with cullin 1 E3 ubiquitin ligase to facilitate its recruitment to STAT2. Consequently, BGLF2 suppressed ISG induction by IFN-β. Furthermore, BGLF2 also suppressed type II and type III IFN signaling, although the suppressive effect on type II IFN response was milder. When pretreated with IFN-β, host cells became less susceptible to primary infection of EBV. This phenotype was reversed when expression of BGLF2 was enforced. Finally, genetic disruption of BGLF2 in EBV led to more pronounced induction of ISGs. Our study unveils the roles of BGLF2 not only in the subversion of innate IFN response but also in lytic infection and reactivation of EBV. IMPORTANCE Epstein-Barr virus (EBV) is an oncogenic virus associated with the development of lymphoid and epithelial malignancies. EBV has to subvert interferon-mediated host antiviral response to replicate and cause diseases. It is therefore of great interest to identify and characterize interferon-antagonizing proteins produced by EBV. In this study, we perform a screen to search for EBV proteins that suppress the action of interferons. We further show that BGLF2 protein of EBV is particularly strong in this suppression. This is achieved by inhibiting two key proteins STAT1 and STAT2 that mediate the antiviral activity of interferons. BGLF2 recruits a host enzyme to remove the phosphate group from STAT1 thereby inactivating its activity. BGLF2 also redirects STAT2 for degradation. A recombinant virus in which BGLF2 gene has been disrupted can activate host interferon response more robustly. Our findings reveal a novel mechanism by which EBV BGLF2 protein suppresses interferon signaling.
- Published
- 2021
3. Suppression of JAK-STAT Signaling by Epstein-Barr Virus Tegument Protein BGLF2 through Recruitment of SHP1 Phosphatase and Promotion of STAT2 Degradation
- Author
-
Jangra, Sonia, primary, Bharti, Aradhana, additional, Lui, Wai-Yin, additional, Chaudhary, Vidyanath, additional, Botelho, Michael George, additional, Yuen, Kit-San, additional, and Jin, Dong-Yan, additional
- Published
- 2021
- Full Text
- View/download PDF
4. NF-κB Signaling Regulates Expression of Epstein-Barr Virus BART MicroRNAs and Long Noncoding RNAs in Nasopharyngeal Carcinoma
- Author
-
Dong-Yan Jin, Shuang Tong, Jianji Pan, Gaohong Zhang, Mei-Ru Chen, Yixin Chen, Jingfeng Zong, Honglin Chen, and Rob J. A. Verhoeven
- Subjects
Gene Expression Regulation, Viral ,0301 basic medicine ,Epstein-Barr Virus Infections ,Herpesvirus 4, Human ,Immunology ,Nasopharyngeal neoplasm ,Biology ,medicine.disease_cause ,Microbiology ,Viral Matrix Proteins ,03 medical and health sciences ,Virology ,microRNA ,Virus latency ,Tumor Cells, Cultured ,otorhinolaryngologic diseases ,medicine ,Humans ,Spotlight ,Promoter Regions, Genetic ,Regulation of gene expression ,Nasopharyngeal Carcinoma ,Base Sequence ,Deoxyribonuclease BamHI ,Carcinoma ,NF-kappa B ,Nasopharyngeal Neoplasms ,medicine.disease ,Epstein–Barr virus ,Virus Latency ,Virus-Cell Interactions ,MicroRNAs ,stomatognathic diseases ,030104 developmental biology ,Nasopharyngeal carcinoma ,Insect Science ,Cancer research ,RNA, Viral ,RNA, Long Noncoding ,Carcinogenesis ,Chromatin immunoprecipitation ,Signal Transduction - Abstract
Epstein-Barr virus (EBV) expresses few viral proteins in nasopharyngeal carcinoma (NPC) but high levels of BamHI-A rightward transcripts (BARTs), which include long noncoding RNAs (lncRNAs) and BART microRNAs (miRNAs). It is hypothesized that the mechanism for regulation of BARTs may relate to EBV pathogenesis in NPC. We showed that nuclear factor-κB (NF-κB) activates the BART promoters and modulates the expression of BARTs in EBV-infected NPC cells but that introduction of mutations into the putative NF-κB binding sites abolished activation of BART promoters by NF-κB. Binding of p50 subunits to NF-κB sites in the BART promoters was confirmed in electrophoretic mobility shift assays (EMSA) and further demonstrated in vivo using chromatin immunoprecipitation (ChIP) analysis. Expression of BART miRNAs and lncRNAs correlated with NF-κB activity in EBV-infected epithelial cells, while treatment of EBV-harboring NPC C666-1 cells with aspirin (acetylsalicylic acid [ASA]) and the IκB kinase inhibitor PS-1145 inhibited NF-κB activity, resulting in downregulation of BART expression. Expression of EBV LMP1 activates BART promoters, whereas an LMP1 mutant which cannot induce NF-κB activation does not activate BART promoters, further supporting the idea that expression of BARTs is regulated by NF-κB signaling. Expression of LMP1 is tightly regulated in NPC cells, and this study confirmed that miR-BART5-5p downregulates LMP1 expression, suggesting a feedback loop between BART miRNA and LMP1-mediated NF-κB activation in the NPC setting. These findings provide new insights into the mechanism underlying the deregulation of BARTs in NPC and identify a regulatory loop through which BARTs support EBV latency in NPC. IMPORTANCE Nasopharyngeal carcinoma (NPC) cells are ubiquitously infected with Epstein-Barr virus (EBV). Notably, EBV expresses very few viral proteins in NPC cells, presumably to avoid triggering an immune response, but high levels of EBV BART miRNAs and lncRNAs which exhibit complex functions associated with EBV pathogenesis. The mechanism for regulation of BARTs is critical for understanding NPC oncogenesis. This study provides multiple lines of evidence to show that expression of BARTs is subject to regulation by NF-κB signaling. EBV LMP1 is a potent activator of NF-κB signaling, and we demonstrate that LMP1 can upregulate expression of BARTs through NF-κB signaling and that BART miRNAs are also able to downregulate LMP1 expression. It appears that aberrant NF-κB signaling and expression of BARTs form an autoregulatory loop for maintaining EBV latency in NPC cells. Further exploration of how targeting NF-κB signaling interrupts EBV latency in NPC cells may reveal new options for NPC treatment.
- Published
- 2016
5. Comparative Analysis of Gammaherpesvirus Circular RNA Repertoires: Conserved and Unique Viral Circular RNAs
- Author
-
Ungerleider, Nathan A., primary, Jain, Vaibhav, additional, Wang, Yiping, additional, Maness, Nicholas J., additional, Blair, Robert V., additional, Alvarez, Xavier, additional, Midkiff, Cecily, additional, Kolson, Dennis, additional, Bai, Shanshan, additional, Roberts, Claire, additional, Moss, Walter N., additional, Wang, Xia, additional, Serfecz, Jacqueline, additional, Seddon, Michael, additional, Lehman, Terri, additional, Ma, Tianfang, additional, Dong, Yan, additional, Renne, Rolf, additional, Tibbetts, Scott A., additional, and Flemington, Erik K., additional
- Published
- 2019
- Full Text
- View/download PDF
6. Selective Activation of Type II Interferon Signaling by Zika Virus NS5 Protein
- Author
-
Kin-Hang Kok, Vidyanath Chaudhary, Kwok-Yung Yuen, Dong-Yan Jin, Shuo Zhang, Mifang Liang, Ching-Ping Chan, Pei-Hui Wang, Chi-Ping Chan, Jian-Piao Cai, Kit-San Yuen, and Jasper Fuk-Woo Chan
- Subjects
0301 basic medicine ,viruses ,030106 microbiology ,Immunology ,Viral Nonstructural Proteins ,Microbiology ,Proinflammatory cytokine ,Cell Line ,03 medical and health sciences ,Interferon-gamma ,Interferon ,Virology ,medicine ,Gene silencing ,CXCL10 ,Humans ,Interferon gamma ,STAT1 ,STAT2 ,biology ,STAT2 Transcription Factor ,Zika Virus ,030104 developmental biology ,Viral replication ,Insect Science ,biology.protein ,Pathogenesis and Immunity ,medicine.drug ,Protein Binding ,Signal Transduction - Abstract
Severe complications of Zika virus (ZIKV) infection might be caused by inflammation, but how ZIKV induces proinflammatory cytokines is not understood. In this study, we show opposite regulatory effects of the ZIKV NS5 protein on interferon (IFN) signaling. Whereas ZIKV and its NS5 protein were potent suppressors of type I and type III IFN signaling, they were found to activate type II IFN signaling. Inversely, IFN-γ augmented ZIKV replication. NS5 interacted with STAT2 and targeted it for ubiquitination and degradation, but it had no influence on STAT1 stability or nuclear translocation. The recruitment of STAT1-STAT2-IRF9 to IFN-β-stimulated genes was compromised when NS5 was expressed. Concurrently, the formation of STAT1-STAT1 homodimers and their recruitment to IFN-γ-stimulated genes, such as the gene encoding the proinflammatory cytokine CXCL10, were augmented. Silencing the expression of an IFN-γ receptor subunit or treatment of ZIKV-infected cells with a JAK2 inhibitor suppressed viral replication and viral induction of IFN-γ-stimulated genes. Taken together, our findings provide a new mechanism by which the ZIKV NS5 protein differentially regulates IFN signaling to facilitate viral replication and cause diseases. This activity might be shared by a group of viral IFN modulators. IMPORTANCE Mammalian cells produce three types of interferons to combat viral infection and to control host immune responses. To replicate and cause diseases, pathogenic viruses have developed different strategies to defeat the action of host interferons. Many viral proteins, including the Zika virus (ZIKV) NS5 protein, are known to be able to suppress the antiviral property of type I and type III interferons. Here we further show that the ZIKV NS5 protein can also boost the activity of type II interferon to induce cellular proteins that promote inflammation. This is mediated by the differential effect of the ZIKV NS5 protein on a pair of cellular transcription factors, STAT1 and STAT2. NS5 induces the degradation of STAT2 but promotes the formation of STAT1-STAT1 protein complexes, which activate genes controlled by type II interferon. A drug that specifically inhibits the IFN-γ receptor or STAT1 shows an anti-ZIKV effect and might also have anti-inflammatory activity.
- Published
- 2017
7. Middle East Respiratory Syndrome Coronavirus 4a Protein Is a Double-Stranded RNA-Binding Protein That Suppresses PACT-Induced Activation of RIG-I and MDA5 in the Innate Antiviral Response
- Author
-
Kit-San Yuen, Chun Kew, Pak Yin Lui, Dong-Yan Jin, Man Lung Yeung, Patrick C. Y. Woo, Kin-Hang Kok, Chi-Ping Chan, Kwok-Yung Yuen, Kam Leung Siu, and Herman Tse
- Subjects
RIG-I ,Middle East respiratory syndrome coronavirus ,viruses ,Immunology ,virus diseases ,biochemical phenomena, metabolism, and nutrition ,Biology ,medicine.disease_cause ,Type I interferon production ,biology.organism_classification ,Microbiology ,Virology ,Virus ,Sendai virus ,Virus-Cell Interactions ,respiratory tract diseases ,Double-stranded RNA binding ,Insect Science ,medicine ,Viral structural protein ,Coronavirus - Abstract
Middle East respiratory syndrome coronavirus (MERS-CoV) is an emerging pathogen that causes severe disease in human. MERS-CoV is closely related to bat coronaviruses HKU4 and HKU5. Evasion of the innate antiviral response might contribute significantly to MERS-CoV pathogenesis, but the mechanism is poorly understood. In this study, we characterized MERS-CoV 4a protein as a novel immunosuppressive factor that antagonizes type I interferon production. MERS-CoV 4a protein contains a double-stranded RNA-binding domain capable of interacting with poly(I·C). Expression of MERS-CoV 4a protein suppressed the interferon production induced by poly(I·C) or Sendai virus. RNA binding of MERS-CoV 4a protein was required for IFN antagonism, a property shared by 4a protein of bat coronavirus HKU5 but not by the counterpart in bat coronavirus HKU4. MERS-CoV 4a protein interacted with PACT in an RNA-dependent manner but not with RIG-I or MDA5. It inhibited PACT-induced activation of RIG-I and MDA5 but did not affect the activity of downstream effectors such as RIG-I, MDA5, MAVS, TBK1, and IRF3. Taken together, our findings suggest a new mechanism through which MERS-CoV employs a viral double-stranded RNA-binding protein to circumvent the innate antiviral response by perturbing the function of cellular double-stranded RNA-binding protein PACT. PACT targeting might be a common strategy used by different viruses, including Ebola virus and herpes simplex virus 1, to counteract innate immunity. IMPORTANCE Middle East respiratory syndrome coronavirus (MERS-CoV) is an emerging and highly lethal human pathogen. Why MERS-CoV causes severe disease in human is unclear, and one possibility is that MERS-CoV is particularly efficient in counteracting host immunity, including the sensing of virus invasion. It will therefore be critical to clarify how MERS-CoV cripples the host proteins that sense viruses and to compare MERS-CoV with its ancestral viruses in bats in the counteraction of virus sensing. This work not only provides a new understanding of the abilities of MERS-CoV and closely related bat viruses to subvert virus sensing but also might prove useful in revealing new strategies for the development of vaccines and antivirals.
- Published
- 2014
8. A Screen for Epstein-Barr Virus Proteins That Inhibit the DNA Damage Response Reveals a Novel Histone Binding Protein
- Author
-
Ho, Ting-Hin, primary, Sitz, Justine, additional, Shen, Qingtang, additional, Leblanc-Lacroix, Ariane, additional, Campos, Eric I., additional, Borozan, Ivan, additional, Marcon, Edyta, additional, Greenblatt, Jack, additional, Fradet-Turcotte, Amelie, additional, Jin, Dong-Yan, additional, and Frappier, Lori, additional
- Published
- 2018
- Full Text
- View/download PDF
9. PACT- and RIG-I-Dependent Activation of Type I Interferon Production by a Defective Interfering RNA Derived from Measles Virus Vaccine
- Author
-
Dong-Yan Jin, T. H. Ho, Kin-Hang Kok, Shizuo Akira, Chun Kew, Takashi Satoh, Chi-Ping Chan, and Pak-Yin Lui
- Subjects
0301 basic medicine ,Models, Molecular ,Immunology ,Measles Vaccine ,Cellular Response to Infection ,Pact ,Microbiology ,Defective virus ,Virus ,Cell Line ,Measles virus ,DEAD-box RNA Helicases ,03 medical and health sciences ,0302 clinical medicine ,Interferon ,Virology ,medicine ,Humans ,Receptors, Immunologic ,biology ,RIG-I ,RNA ,Defective Viruses ,RNA-Binding Proteins ,Interferon-beta ,biology.organism_classification ,Type I interferon production ,030104 developmental biology ,Insect Science ,DEAD Box Protein 58 ,Nucleic Acid Conformation ,RNA, Viral ,030215 immunology ,medicine.drug - Abstract
The live attenuated measles virus vaccine is highly immunostimulatory. Identification and characterization of its components that activate the innate immune response might provide new strategies and agents for the rational design and development of chemically defined adjuvants. In this study, we report on the activation of type I interferon (IFN) production by a defective interfering (DI) RNA isolated from the Hu-191 vaccine strain of measles virus. We found that the Hu-191 virus induced IFN-β much more potently than the Edmonston strain. In the search for IFN-inducing species in Hu-191, we identified a DI RNA specifically expressed by this strain. This DI RNA, which was of the copy-back type, was predicted to fold into a hairpin structure with a long double-stranded stem region of 206 bp, and it potently induced the expression of IFN-β. Its IFN-β-inducing activity was further enhanced when both cytoplasmic RNA sensor RIG-I and its partner, PACT, were overexpressed. On the contrary, this activity was abrogated in cells deficient in PACT or RIG-I. The DI RNA was found to be associated with PACT in infected cells. In addition, both the 5′-di/triphosphate end and the double-stranded stem region on the DI RNA were essential for its activation of PACT and RIG-I. Taken together, our findings support a model in which a viral DI RNA is sensed by PACT and RIG-I to initiate an innate antiviral response. Our work might also provide a foundation for identifying physiological PACT ligands and developing novel adjuvants or antivirals. IMPORTANCE The live attenuated measles virus vaccine is one of the most successful human vaccines and has largely contained the devastating impact of a highly contagious virus. Identifying the components in this vaccine that stimulate the host immune response and understanding their mechanism of action might help to design and develop better adjuvants, vaccines, antivirals, and immunotherapeutic agents. We identified and characterized a defective interfering RNA from the Hu-191 vaccine strain of measles virus which has safely been used in millions of people for many years. We further demonstrated that this RNA potently induces an antiviral immune response through cellular sensors of viral RNA known as PACT and RIG-I. Similar types of viral RNA that bind with and activate PACT and RIG-I might retain the immunostimulatory property of measles virus vaccines but would not induce adaptive immunity. They are potentially useful as chemically defined vaccine adjuvants, antivirals, and immunostimulatory agents.
- Published
- 2015
10. Natural Occurrence and Characterization of Two Internal Ribosome Entry Site Elements in a Novel Virus, Canine Picodicistrovirus, in the Picornavirus-Like Superfamily
- Author
-
Yi Huang, Susanna K. P. Lau, Kwok-Hung Chan, Kwok-Yung Yuen, Jade L. L. Teng, Man Lung Yeung, Garnet K. Y. Choi, Patrick C. Y. Woo, Dong-Yan Jin, Hoi-Wah Tsoi, and Herman Tse
- Subjects
Picornavirus ,viruses ,Molecular Sequence Data ,Immunology ,Genome, Viral ,Picornaviridae ,Microbiology ,Virus ,Open Reading Frames ,Dogs ,Virology ,Picornaviridae - chemistry - classification - genetics - isolation and purification ,Animals ,Gene ,Disease Reservoirs - virology ,Ribosomes - genetics - metabolism ,Phylogeny ,Disease Reservoirs ,Genetics ,Dicistroviridae ,Base Sequence ,biology ,Helicase ,RNA ,biology.organism_classification ,Internal ribosome entry site ,Genetic Diversity and Evolution ,Protein Biosynthesis ,Insect Science ,Novel virus ,biology.protein ,Nucleic Acid Conformation ,RNA, Viral ,5' Untranslated Regions ,Ribosomes ,Dogs - virology - Abstract
Dicistroviridae and Picornaviridae are two phylogenetically related families of positive-sense single-stranded RNA viruses in the picornavirus-like superfamily with similar gene contents but different genome organizations and hosts. In a surveillance study involving 1,472 samples from 368 dogs over a 22-month period, we identified a novel picornavirus-like virus from 47 fecal and urine samples by the use of reverse transcription-PCR (RT-PCR). Sequencing and phylogenetic analysis of three complete genomes revealed that, although it seemed that the virus was most closely related to other picornaviruses, P1, P2, and P3 of the virus possessed very low amino acid identities of, link_to_OA_fulltext
- Published
- 2011
- Full Text
- View/download PDF
11. Selective Activation of Type II Interferon Signaling by Zika Virus NS5 Protein
- Author
-
Chaudhary, Vidyanath, primary, Yuen, Kit-San, additional, Chan, Jasper Fuk-Woo, additional, Chan, Ching-Ping, additional, Wang, Pei-Hui, additional, Cai, Jian-Piao, additional, Zhang, Shuo, additional, Liang, Mifang, additional, Kok, Kin-Hang, additional, Chan, Chi-Ping, additional, Yuen, Kwok-Yung, additional, and Jin, Dong-Yan, additional
- Published
- 2017
- Full Text
- View/download PDF
12. Modulation of the Unfolded Protein Response by the Severe Acute Respiratory Syndrome Coronavirus Spike Protein
- Author
-
Kam-Leung Siu, Kwok-Yung Yuen, Dong-Yan Jin, Ching-Ping Chan, Bo-Jian Zheng, and King-Tung Chin
- Subjects
Protein Denaturation ,viruses ,Immunology ,Activating transcription factor ,Biology ,medicine.disease_cause ,Endoplasmic Reticulum ,Microbiology ,Cell Line ,Viral Envelope Proteins ,Virology ,Heat shock protein ,Chlorocebus aethiops ,medicine ,Animals ,Humans ,HSP70 Heat-Shock Proteins ,Endoplasmic Reticulum Chaperone BiP ,Vero Cells ,Heat-Shock Proteins ,Coronavirus ,Membrane Glycoproteins ,Ccaat-enhancer-binding proteins ,Endoplasmic reticulum ,fungi ,Membrane Proteins ,Molecular biology ,Virus-Cell Interactions ,Membrane protein ,Severe acute respiratory syndrome-related coronavirus ,Insect Science ,Spike Glycoprotein, Coronavirus ,Unfolded protein response ,CCAAT-Enhancer-Binding Proteins ,Signal transduction ,Molecular Chaperones ,Plasmids - Abstract
Perturbation of the function of endoplasmic reticulum (ER) causes stress leading to the activation of cell signaling pathways known as the unfolded protein response (UPR). Severe acute respiratory syndrome (SARS) coronavirus (SARS-CoV) uses ER as a site for synthesis and processing of viral proteins. In this report, we demonstrate that infection with SARS-CoV induces the UPR in cultured cells. A comparison with M, E, and NSP6 proteins indicates that SARS-CoV spike (S) protein sufficiently induces transcriptional activation of several UPR effectors, including glucose-regulated protein 78 (GRP78), GRP94, and C/EBP homologous protein. A substantial amount of S protein accumulates in the ER. The expression of S protein exerts different effects on the three major signaling pathways of the UPR. Particularly, it induces GRP78/94 through PKR-like ER kinase but has no influence on activating transcription factor 6 or X box-binding protein 1. Taken together, our findings suggest that SARS-CoV S protein specifically modulates the UPR to facilitate viral replication.
- Published
- 2006
- Full Text
- View/download PDF
13. TORC1 and TORC2 Coactivators Are Required for Tax Activation of the Human T-Cell Leukemia Virus Type 1 Long Terminal Repeats
- Author
-
Dong-Yan Jin, Kam-Leung Siu, King-Tung Chin, Elizabeth Yee Wai Choy, YT Siu, and Kuan-Teh Jeang
- Subjects
Gene Expression Regulation, Viral ,Transcription, Genetic ,Torc ,viruses ,Immunology ,P300-CBP Transcription Factors ,Activating Transcription Factor 4 ,CREB ,Microbiology ,Transcription (biology) ,Virology ,Humans ,p300-CBP Transcription Factors ,Cyclic AMP Response Element-Binding Protein ,Transcription factor ,health care economics and organizations ,Genetics ,Human T-lymphotropic virus 1 ,biology ,Terminal Repeat Sequences ,Gene Products, tax ,Phosphoproteins ,Coactivation ,Long terminal repeat ,Genome Replication and Regulation of Viral Gene Expression ,Insect Science ,Trans-Activators ,biology.protein ,Virus Activation ,HeLa Cells ,Protein Binding ,Transcription Factors - Abstract
Human T-cell leukemia virus type 1 (HTLV-1) Tax protein activates viral transcription from the long terminal repeats (LTR). Mechanisms through which Tax activates LTR have been established, but coactivators of this process remain to be identified and characterized. Here we show that all three members of the TORC family of transcriptional regulators are coactivators of Tax for LTR-driven expression. TORC coactivation requires CREB, but not ATF4 or other bZIP factors. Tax physically interacts with TORC1, TORC2, and TORC3 (TORC1/2/3), and the depletion of TORC1/2/3 inhibited Tax activity. TORC coactivation can be further enhanced by transcriptional coactivator p300. In addition, coactivators in the p300 family are required for full activity of Tax independently of TORC1/2/3. Thus, both TORC and p300 families of coactivators are essential for optimal activation of HTLV-1 transcription by Tax.
- Published
- 2006
14. NF-κB Signaling Regulates Expression of Epstein-Barr Virus BART MicroRNAs and Long Noncoding RNAs in Nasopharyngeal Carcinoma
- Author
-
Verhoeven, Rob J. A., primary, Tong, Shuang, additional, Zhang, Gaohong, additional, Zong, Jingfeng, additional, Chen, Yixin, additional, Jin, Dong-Yan, additional, Chen, Mei-Ru, additional, Pan, Jianji, additional, and Chen, Honglin, additional
- Published
- 2016
- Full Text
- View/download PDF
15. Suppression of Type I Interferon Production by Human T-Cell Leukemia Virus Type 1 Oncoprotein Tax through Inhibition of IRF3 Phosphorylation
- Author
-
Yuen, Chun-Kit, primary, Chan, Ching-Ping, additional, Fung, Sin-Yee, additional, Wang, Pei-Hui, additional, Wong, Wan-Man, additional, Tang, Hei-Man Vincent, additional, Yuen, Kit-San, additional, Chan, Chi-Ping, additional, Jin, Dong-Yan, additional, and Kok, Kin-Hang, additional
- Published
- 2016
- Full Text
- View/download PDF
16. PACT- and RIG-I-Dependent Activation of Type I Interferon Production by a Defective Interfering RNA Derived from Measles Virus Vaccine
- Author
-
Ho, Ting-Hin, primary, Kew, Chun, additional, Lui, Pak-Yin, additional, Chan, Chi-Ping, additional, Satoh, Takashi, additional, Akira, Shizuo, additional, Jin, Dong-Yan, additional, and Kok, Kin-Hang, additional
- Published
- 2016
- Full Text
- View/download PDF
17. SIRT1 Suppresses Human T-Cell Leukemia Virus Type 1 Transcription
- Author
-
Tang, Hei-Man Vincent, primary, Gao, Wei-Wei, additional, Chan, Chi-Ping, additional, Cheng, Yun, additional, Deng, Jian-Jun, additional, Yuen, Kit-San, additional, Iha, Hidekatsu, additional, and Jin, Dong-Yan, additional
- Published
- 2015
- Full Text
- View/download PDF
18. New Noncoding Lytic Transcripts Derived from the Epstein-Barr Virus Latency Origin of Replication, oriP , Are Hyperedited, Bind the Paraspeckle Protein, NONO/p54nrb, and Support Viral Lytic Transcription
- Author
-
Cao, Subing, primary, Moss, Walter, additional, O'Grady, Tina, additional, Concha, Monica, additional, Strong, Michael J., additional, Wang, Xia, additional, Yu, Yi, additional, Baddoo, Melody, additional, Zhang, Kun, additional, Fewell, Claire, additional, Lin, Zhen, additional, Dong, Yan, additional, and Flemington, Erik K., additional
- Published
- 2015
- Full Text
- View/download PDF
19. Occurrence and Reassortment of Avian Influenza A (H7N9) Viruses Derived from Coinfected Birds in China
- Author
-
Liu, Wei, primary, Fan, Hang, additional, Raghwani, Jayna, additional, Lam, Tommy Tsan-Yuk, additional, Li, Jing, additional, Pybus, Oliver G., additional, Yao, Hong-Wu, additional, Wo, Ying, additional, Liu, Kun, additional, An, Xiao-Ping, additional, Pei, Guang-Qian, additional, Li, Hao, additional, Wang, Hong-Yu, additional, Zhao, Jian-Jun, additional, Jiang, Tao, additional, Ma, Mai-Juan, additional, Xia, Xian, additional, Dong, Yan-De, additional, Zhao, Tong-Yan, additional, Jiang, Jia-Fu, additional, Yang, Yin-Hui, additional, Guan, Yi, additional, Tong, Yigang, additional, and Cao, Wu-Chun, additional
- Published
- 2014
- Full Text
- View/download PDF
20. Middle East Respiratory Syndrome Coronavirus 4a Protein Is a Double-Stranded RNA-Binding Protein That Suppresses PACT-Induced Activation of RIG-I and MDA5 in the Innate Antiviral Response
- Author
-
Siu, Kam-Leung, primary, Yeung, Man Lung, additional, Kok, Kin-Hang, additional, Yuen, Kit-San, additional, Kew, Chun, additional, Lui, Pak-Yin, additional, Chan, Chi-Ping, additional, Tse, Herman, additional, Woo, Patrick C. Y., additional, Yuen, Kwok-Yung, additional, and Jin, Dong-Yan, additional
- Published
- 2014
- Full Text
- View/download PDF
21. Suppression of PACT-Induced Type I Interferon Production by Herpes Simplex Virus 1 Us11 Protein
- Author
-
Kew, Chun, primary, Lui, Pak-Yin, additional, Chan, Chi-Ping, additional, Liu, Xiang, additional, Au, Shannon Wing Ngor, additional, Mohr, Ian, additional, Jin, Dong-Yan, additional, and Kok, Kin-Hang, additional
- Published
- 2013
- Full Text
- View/download PDF
22. Genetic evidence of a role for ATM in functional interaction between human T-cell leukemia virus type 1 Tax and p53
- Author
-
Kyong-Wook Yim, Phillip L. Van, Dong-Yan Jin, Kuan-Teh Jeang, George Dapolito, and Akihiro Kurimasa
- Subjects
Immunology ,Cell Cycle Proteins ,Ataxia Telangiectasia Mutated Proteins ,DNA-Activated Protein Kinase ,Protein Serine-Threonine Kinases ,Gene Products, tax - physiology ,CREB ,medicine.disease_cause ,Microbiology ,Jurkat cells ,Transformation and Oncogenesis ,Protein-Serine-Threonine Kinases - physiology ,Virology ,medicine ,Humans ,Nuclear protein ,Phosphorylation ,Cyclic AMP Response Element-Binding Protein ,Tumor Suppressor Protein p53 - physiology ,Mutation ,Human T-lymphotropic virus 1 ,biology ,Tumor Suppressor Proteins ,Human T-lymphotropic virus 2 ,Human T-lymphotropic virus 1 - physiology ,NF-kappa B ,Nuclear Proteins ,Gene Products, tax ,biology.organism_classification ,NFKB1 ,Molecular biology ,Cell biology ,DNA-Binding Proteins ,Repressor Proteins ,Cell culture ,Insect Science ,biology.protein ,Tumor Suppressor Protein p53 ,HeLa Cells - Abstract
Recent evidence from several investigators suggest that the human T-cell leukemia virus type 1 Tax oncoprotein represses the transcriptional activity of the tumor suppressor protein, p53. An examination of published findings reveals serious controversy as to the mechanism(s) utilized by Tax to inhibit p53 activity and whether the same mechanism is used by Tax in adherent and suspension cells. Here, we have investigated Tax-p53 interaction simultaneously in adherent epithelial (HeLa and Saos) and suspension T-lymphocyte (Jurkat) cells. Our results indicate that Tax activity through the CREB/CREB-binding protein (CBP), but not NF-κB, pathway is needed to repress the transcriptional activity of p53 in all tested cell lines. However, we did find that while CBP binding by Tax is necessary, it is not sufficient for inhibiting p53 function. Based on knockout cell studies, we correlated a strong genetic requirement for the ATM, but not protein kinase-dependent DNA, protein in conferring a Tax-p53-repressive phenotype., published_or_final_version
- Published
- 2000
23. Natural Occurrence and Characterization of Two Internal Ribosome Entry Site Elements in a Novel Virus, Canine Picodicistrovirus, in the Picornavirus-Like Superfamily
- Author
-
Woo, Patrick C. Y., primary, Lau, Susanna K. P., additional, Choi, Garnet K. Y., additional, Huang, Yi, additional, Teng, Jade L. L., additional, Tsoi, Hoi-Wah, additional, Tse, Herman, additional, Yeung, Man Lung, additional, Chan, Kwok-Hung, additional, Jin, Dong-Yan, additional, and Yuen, Kwok-Yung, additional
- Published
- 2012
- Full Text
- View/download PDF
24. Modulation of the Unfolded Protein Response by the Severe Acute Respiratory Syndrome Coronavirus Spike Protein
- Author
-
Chan, Ching-Ping, primary, Siu, Kam-Leung, additional, Chin, King-Tung, additional, Yuen, Kwok-Yung, additional, Zheng, Bojian, additional, and Jin, Dong-Yan, additional
- Published
- 2006
- Full Text
- View/download PDF
25. TORC1 and TORC2 Coactivators Are Required for Tax Activation of the Human T-Cell Leukemia Virus Type 1 Long Terminal Repeats
- Author
-
Siu, Yeung-Tung, primary, Chin, King-Tung, additional, Siu, Kam-Leung, additional, Yee Wai Choy, Elizabeth, additional, Jeang, Kuan-Teh, additional, and Jin, Dong-Yan, additional
- Published
- 2006
- Full Text
- View/download PDF
26. Genetic Evidence of a Role for ATM in Functional Interaction between Human T-Cell Leukemia Virus Type 1 Tax and p53
- Author
-
Van, Phillip L., primary, Yim, Kyong-Wook, additional, Jin, Dong-Yan, additional, Dapolito, George, additional, Kurimasa, Akihiro, additional, and Jeang, Kuan-Teh, additional
- Published
- 2001
- Full Text
- View/download PDF
27. Evolutionary Rate and Genetic Drift of Hepatitis C Virus Are Not Correlated with the Host Immune Response: Studies of Infected Donor-Recipient Clusters
- Author
-
Allain, Jean-Pierre, primary, Dong, Yan, additional, Vandamme, Anne-Mieke, additional, Moulton, Vincent, additional, and Salemi, Marco, additional
- Published
- 2000
- Full Text
- View/download PDF
28. A Screen for Epstein-Barr Virus Proteins That Inhibit the DNA Damage Response Reveals a Novel Histone Binding Protein.
- Author
-
Ting-Hin Ho, Sitz, Justine, Qingtang Shen, Leblanc-Lacroix, Ariane, Campos, Eric I., Borozan, Ivan, Marcon, Edyta, Greenblatt, Jack, Fradet-Turcotte, Amelie, Dong-Yan Jin, and Frappier, Lori
- Subjects
- *
EPSTEIN-Barr virus genetics , *DNA damage , *HISTONES , *CARRIER proteins , *COPYING , *VIRAL genomes - Abstract
To replicate and persist in human cells, linear double-stranded DNA (dsDNA) viruses, such as Epstein-Barr virus (EBV), must overcome the host DNA damage response (DDR) that is triggered by the viral genomes. Since this response is necessary to maintain cellular genome integrity, its inhibition by EBV is likely an important factor in the development of cancers associated with EBV infection, including gastric carcinoma. Here we present the first extensive screen of EBV proteins that inhibit dsDNA break signaling. We identify the BKRF4 tegument protein as a DDR inhibitor that interferes with histone ubiquitylation at ds-DNA breaks and recruitment of the RNF168 histone ubiquitin ligase. We further show that BKRF4 binds directly to histones through an acidic domain that targets BKRF4 to cellular chromatin and is sufficient to inhibit dsDNA break signaling. BKRF4 transcripts were detected in EBV-positive gastric carcinoma cells (AGS-EBV), and these increased in lytic infection. Silencing of BKRF4 in both latent and lytic AGS-EBV cells (but not in EBV-negative AGS cells) resulted in increased dsDNA break signaling, confirming a role for BKRF4 in DDR inhibition in the context of EBV infection and suggesting that BKRF4 is expressed in latent cells. BKRF4 was also found to be consistently expressed in EBV-positive gastric tumors in the absence of a full lytic infection. The results suggest that BKRF4 plays a role in inhibiting the cellular DDR in latent and lytic EBV infection and that the resulting accumulation of DNA damage might contribute to development of gastric carcinoma. [ABSTRACT FROM AUTHOR]
- Published
- 2018
- Full Text
- View/download PDF
29. Retraction for Siu et al., "Middle East Respiratory Syndrome Coronavirus 4a Protein Is a Double-Stranded RNA-Binding Protein That Suppresses PACT-Induced Activation of RIG-I and MDA5 in the Innate Antiviral Response".
- Author
-
Kam-Leung Siu, Man Lung Yeung, Kin-Hang Kok, Kit-San Yuen, Chun Kew, Pak-Yin Lui, Chi-Ping Chan, Herman Tse, Woo, Patrick C. Y., Kwok-Yung Yuen, and Dong-Yan Jin
- Subjects
- *
MERS coronavirus , *RNA-binding proteins - Published
- 2022
- Full Text
- View/download PDF
30. Suppression of Type I Interferon Production by Human T-Cell Leukemia Virus Type 1 Oncoprotein Tax through Inhibition of IRF3 Phosphorylation.
- Author
-
Chun-Kit Yuen, Ching-Ping Chan, Sin-Yee Fung Fung, Pei-Hui Wang, Wan-Man Wong, Hei-Man Vincent Tang, Kit-San Yuen, Chi-Ping Chan, Dong-Yan Jin, and Kin-Hang Kok
- Subjects
- *
TYPE I interferons , *HTLV-I , *INTERFERON regulatory factors , *REVERSE transcriptase inhibitors , *PHOSPHORYLATION , *ADULT T-cell leukemia , *AZIDOTHYMIDINE , *PARAPARESIS - Abstract
Infection with human T-cell leukemia virus type 1 (HTLV-1) is associated with adult T-cell leukemia (ATL) and tropical spastic paraparesis. Type I interferons (IFNs) are key effectors of the innate antiviral response, and IFN-β combined with the nucleoside reverse transcriptase inhibitor zidovudine is considered the standard first-line therapy for ATL. HTLV-1 oncoprotein Tax is known to suppress innate IFN production and response but the underlying mechanisms remain to be fully established. In this study, we report on the suppression of type I IFN production by HTLV-1 Tax through interaction with and inhibition of TBK1 kinase that phosphorylates IRF3. Induced transcription of IFN-β was severely impaired in HTLV-1-transformed ATL cells and freshly infected T lymphocytes. The ability to suppress IRF3 activation was ascribed to Tax. The expression of Tax alone sufficiently repressed the induction of IFN production by RIG-I plus PACT, cGAMP synthase plus STING, TBK1, IKKβ, IRF3, and IRF7, but not by IRF3-5D, a dominant-active phosphomimetic mutant. This suggests that Tax perturbs IFN production at the step of IRF3 phosphorylation. Tax mutants deficient for CREB or NF-βB activation were fully competent in the suppression of IFN production. Coimmunoprecipitation experiments confirmed the association of Tax with TBK1, IKKβ, STING, and IRF3. In vitro kinase assay indicated an inhibitory effect of Tax on TBK1-mediated phosphorylation of IRF3. Taken together, our findings suggested a new mechanism by which HTLV-1 oncoprotein Tax circumvents the production of type I IFNs in infected cells. Our findings have implications in therapeutic intervention of ATL. [ABSTRACT FROM AUTHOR]
- Published
- 2016
- Full Text
- View/download PDF
31. PACT- and RIG-I-Dependent Activation of Type I Interferon Production by a Defective Interfering RNA Derived from Measles Virus Vaccine.
- Author
-
Ting-Hin Ho, Chun Kew, Pak-Yin Lui, Chi-Ping Chan, Takashi Satoh, Shizuo Akira, Dong-Yan Jin, and Kin-Hang Kok
- Subjects
- *
VIRAL vaccines , *INTERFERONS , *MEASLES virus , *DEFECTIVE interfering RNA , *GENETIC overexpression - Abstract
The live attenuated measles virus vaccine is highly immunostimulatory. Identification and characterization of its components that activate the innate immune response might provide new strategies and agents for the rational design and development of chemically defined adjuvants. In this study, we report on the activation of type I interferon (IFN) production by a defective interfering (DI) RNA isolated from the Hu-191 vaccine strain of measles virus. We found that the Hu-191 virus induced IFN-β much more potently than the Edmonston strain. In the search for IFN-inducing species in Hu-191, we identified a DI RNA specifically expressed by this strain. This DI RNA, which was of the copy-back type, was predicted to fold into a hairpin structure with a long double-stranded stem region of 206 bp, and it potently induced the expression of IFN-β. Its IFN-β-inducing activity was further enhanced when both cytoplasmic RNA sensor RIG-I and its partner, PACT, were overexpressed. On the contrary, this activity was abrogated in cells deficient in PACT or RIG-I. The DI RNA was found to be associated with PACT in infected cells. In addition, both the 5=-di/triphosphate end and the double-stranded stem region on the DI RNA were essential for its activation of PACT and RIG-I. Taken together, our findings support a model in which a viral DI RNA is sensed by PACT and RIG-I to initiate an innate antiviral response. Our work might also provide a foundation for identifying physiological PACT ligands and developing novel adjuvants or antivirals. [ABSTRACT FROM AUTHOR]
- Published
- 2016
- Full Text
- View/download PDF
32. SIRT1 Suppresses Human T-Cell Leukemia Virus Type 1 Transcription.
- Author
-
Vincent Tang, Hei-Man, Wei-Wei Gao, Chi-Ping Chan, Yun Cheng, Jian-Jun Deng, Kit-San Yuen, Hidekatsu Iha, and Dong-Yan Jin
- Subjects
- *
LEUKEMIA , *T cells , *LYMPHOCYTES , *HEMATOLOGIC malignancies , *ANEMIA - Abstract
Human T-cell leukemia virus type 1 (HTLV-1)-associated diseases are poorly treatable, and HTLV-1 vaccines are not available. High proviral load is one major risk factor for disease development. HTLV-1 encodes Tax oncoprotein, which activates transcription from viral long terminal repeats (LTR) and various types of cellular promoters. Counteracting Tax function might have prophylactic and therapeutic benefits. In this work, we report on the suppression of Tax activation of HTLV-1 LTR by SIRT1 deacetylase. The transcriptional activity of Tax on the LTR was largely ablated when SIRT1 was overexpressed, but Tax activation of NF-κB was unaffected. On the contrary, the activation of the LTR by Tax was boosted when SIRT1 was depleted. Treatment of cells with resveratrol shunted Tax activity in a SIRT1-dependent manner. The activation of SIRT1 in HTLV-1-transformed T cells by resveratrol potently inhibited HTLV-1 proviral transcription and Tax expression, whereas compromising SIRT1 by specific inhibitors augmented HTLV-1 mRNA expression. The administration of resveratrol also decreased the production of cell-free HTLV-1 virions from MT2 cells and the transmission of HTLV-1 from MT2 cells to uninfected Jurkat cells in coculture. SIRT1 associated with Tax in HTLV-1-transformed T cells. Treatment with resveratrol prevented the interaction of Tax with CREB and the recruitment of CREB, CRTC1, and p300 to Tax-responsive elements in the LTR. Our work demonstrates the negative regulatory function of SIRT1 in Tax activation of HTLV-1 transcription. Small-molecule activators of SIRT1 such as resveratrol might be considered new prophylactic and therapeutic agents in HTLV-1-associated diseases. [ABSTRACT FROM AUTHOR]
- Published
- 2015
- Full Text
- View/download PDF
33. Middle East Respiratory Syndrome Coronavirus 4a Protein Is a Double-Stranded RNA-Binding Protein That Suppresses PACT-Induced Activation of RIG-I and MDA5 in the Innate Antiviral Response.
- Author
-
Kam-Leung Siu, Man Lung Yeung, Kin-Hang Kok, Kit-San Yuen, Chun Kew, Pak-Yin Lui, Chi-Ping Chan, Herman Tse, Woo, Patrick C. Y., Kwok-Yung Yuen, and Dong-Yan Jin
- Subjects
- *
MERS coronavirus , *CORONAVIRUSES , *DOUBLE-stranded RNA , *VIRUSES , *HERPESVIRUS diseases - Abstract
Middle East respiratory syndrome coronavirus (MERS-CoV) is an emerging pathogen that causes severe disease in human. MERS-CoV is closely related to bat coronaviruses HKU4 and HKU5. Evasion of the innate antiviral response might contribute significantly to MERS-CoV pathogenesis, but the mechanism is poorly understood. In this study, we characterized MERS-CoV 4a protein as a novel immunosuppressive factor that antagonizes type I interferon production. MERS-CoV 4a protein contains a double-stranded RNA-binding domain capable of interacting with poly(I·C). Expression of MERS-CoV 4a protein suppressed the interferon production induced by poly(I·C) or Sendai virus. RNA binding of MERS-CoV 4a protein was required for IFN antagonism, a property shared by 4a protein of bat coronavirus HKU5 but not by the counterpart in bat coronavirus HKU4. MERS-CoV 4a protein interacted with PACT in an RNA-dependent manner but not with RIG-I or MDA5. It inhibited PACT-induced activation of RIG-I and MDA5 but did not affect the activity of downstream effectors such as RIG-I, MDA5, MAVS, TBK1, and IRF3. Taken together, our findings suggest a new mechanism through which MERS-CoV employs a viral double-stranded RNA-binding protein to circumvent the innate antiviral response by perturbing the function of cellular double-stranded RNA-binding protein PACT. PACT targeting might be a common strategy used by different viruses, including Ebola virus and herpes simplex virus 1, to counteract innate immunity. [ABSTRACT FROM AUTHOR]
- Published
- 2014
- Full Text
- View/download PDF
34. Suppression of PACT-Induced Type I Interferon Production by Herpes Simplex Virus 1 Us11 Protein.
- Author
-
Chun Kew, Pak-Yin Lui, Chi-Ping Chan, Xiang Liu, Shannon Wing Ngor Au, Mohr, Ian, Dong-Yan Jin, and Kin-Hang Kok
- Subjects
- *
IMMUNOSUPPRESSION , *HERPES simplex virus , *INTERFERONS , *CYTOPLASM , *NATURAL immunity , *FIBROBLASTS - Abstract
Herpes simplex virus 1 (HSV-1) Us11 protein is a double-stranded RNA-binding protein that suppresses type I interferon production through the inhibition of the cytoplasmic RNA sensor RIG-I. Whether additional cellular mediators are involved in this suppression remains to be determined. In this study, we report on the requirement of cellular double-stranded RNA-binding protein PACT for Us11-mediated perturbation of type I interferon production. Us11 associates with PACT tightly to prevent it from binding with and activating RIG-I. The Us11-deficient HSV-1 was indistinguishable from the Us11-proficient virus in the suppression of interferon production when PACT was compromised. More importantly, HSV-1-induced activation of interferon production was abrogated in PACT knockout murine embryonic fibroblasts. Our findings suggest a new mechanism for viral evasion of innate immunity through which a viral double-stranded RNA-binding protein interacts with PACT to circumvent type I interferon production. This mechanism might also be used by other PACT-binding viral interferon-antagonizing proteins such as Ebola virus VP35 and influenza A virus NS1. [ABSTRACT FROM AUTHOR]
- Published
- 2013
- Full Text
- View/download PDF
35. Modulation of the Unfolded Protein Response by the Severe Acute Respiratory Syndrome Coronavirus Spike Protein.
- Author
-
Ching-Ping Chan, Kam-Leung Siu, King-Tung Chin, Kwok-Yung Yuen, Bojian Zheng, and Dong-Yan Jin
- Subjects
- *
ENDOPLASMIC reticulum , *ORGANELLES , *MICROBIAL proteins , *SARS disease , *CORONAVIRUS diseases , *VIRAL proteins - Abstract
Perturbation of the function of endoplasmic reticulum (ER) causes stress leading to the activation of cell signaling pathways known as the unfolded protein response (UPR). Severe acute respiratory syndrome (SARS) coronavirus (SARS-CoV) uses ER as a site for synthesis and processing of viral proteins. In this report, we demonstrate that infection with SARS-CoV induces the UPR in cultured cells. A comparison with M, E, and NSP6 proteins indicates that SARS-CoV spike (S) protein sufficiently induces transcriptional activation of several UPR effectors, including glucose-regulated protein 78 (GRP78), GRP94, and C/EBP homologous protein. A substantial amount of S protein accumulates in the ER. The expression of S protein exerts different effects on the three major signaling pathways of the UPR. Particularly, it induces GRP78/94 through PKR-like ER kinase but has no influence on activating transcription factor 6 or X box-binding protein 1. Taken together, our findings suggest that SARS-CoV S protein specifically modulates the UPR to facilitate viral replication. [ABSTRACT FROM AUTHOR]
- Published
- 2006
- Full Text
- View/download PDF
36. TORC1 and TORC2 Coactivators Are Required for Tax Activation of the Human T-Cell Leukemia Virus Type 1 Long Terminal Repeats.
- Author
-
Yeung-Tung Siu, King-Tung Chin, Kam-Leung Siu, Yee Wai Choy, Elizabeth, Kuan-Teh Jeang, and Dong-Yan Jin
- Subjects
- *
T cells , *LEUKEMIA , *PROTEINS , *ANEMIA , *VIRUSES - Abstract
Human T-cell leukemia virus type 1 (HTLV-1) Tax protein activates viral transcription from the long terminal repeats (LTR). Mechanisms through which Tax activates LTR have been established, but coactivators of this process remain to be identified and characterized. Here we show that all three members of the TORC family of transcriptional regulators are coactivators of Tax for LTR-driven expression. TORC coactivation requires CREB, but not ATF4 or other bZIP factors. Tax physically interacts with TORC1, TORC2, and TORC3 (TORC1/2/3), and the depletion of TORC1/2/3 inhibited Tax activity. TORC coactivation can be further enhanced by transcriptional coactivator p300. In addition, coactivators in the p300 family are required for full activity of Tax independently of TORC1/2/3. Thus, both TORC and p300 families of coactivators are essential for optimal activation of HTLV-1 transcription by Tax. [ABSTRACT FROM AUTHOR]
- Published
- 2006
- Full Text
- View/download PDF
37. PACT- and RIG-I-Dependent Activation of Type I Interferon Production by a Defective Interfering RNA Derived from Measles Virus Vaccine.
- Author
-
Ho TH, Kew C, Lui PY, Chan CP, Satoh T, Akira S, Jin DY, and Kok KH
- Subjects
- Cell Line, DEAD Box Protein 58, Defective Viruses genetics, Humans, Measles Vaccine genetics, Measles virus genetics, Models, Molecular, Nucleic Acid Conformation, RNA, Viral chemistry, Receptors, Immunologic, DEAD-box RNA Helicases metabolism, Defective Viruses immunology, Interferon-beta biosynthesis, Measles Vaccine immunology, Measles virus immunology, RNA, Viral genetics, RNA-Binding Proteins metabolism
- Abstract
Unlabelled: The live attenuated measles virus vaccine is highly immunostimulatory. Identification and characterization of its components that activate the innate immune response might provide new strategies and agents for the rational design and development of chemically defined adjuvants. In this study, we report on the activation of type I interferon (IFN) production by a defective interfering (DI) RNA isolated from the Hu-191 vaccine strain of measles virus. We found that the Hu-191 virus induced IFN-β much more potently than the Edmonston strain. In the search for IFN-inducing species in Hu-191, we identified a DI RNA specifically expressed by this strain. This DI RNA, which was of the copy-back type, was predicted to fold into a hairpin structure with a long double-stranded stem region of 206 bp, and it potently induced the expression of IFN-β. Its IFN-β-inducing activity was further enhanced when both cytoplasmic RNA sensor RIG-I and its partner, PACT, were overexpressed. On the contrary, this activity was abrogated in cells deficient in PACT or RIG-I. The DI RNA was found to be associated with PACT in infected cells. In addition, both the 5'-di/triphosphate end and the double-stranded stem region on the DI RNA were essential for its activation of PACT and RIG-I. Taken together, our findings support a model in which a viral DI RNA is sensed by PACT and RIG-I to initiate an innate antiviral response. Our work might also provide a foundation for identifying physiological PACT ligands and developing novel adjuvants or antivirals., Importance: The live attenuated measles virus vaccine is one of the most successful human vaccines and has largely contained the devastating impact of a highly contagious virus. Identifying the components in this vaccine that stimulate the host immune response and understanding their mechanism of action might help to design and develop better adjuvants, vaccines, antivirals, and immunotherapeutic agents. We identified and characterized a defective interfering RNA from the Hu-191 vaccine strain of measles virus which has safely been used in millions of people for many years. We further demonstrated that this RNA potently induces an antiviral immune response through cellular sensors of viral RNA known as PACT and RIG-I. Similar types of viral RNA that bind with and activate PACT and RIG-I might retain the immunostimulatory property of measles virus vaccines but would not induce adaptive immunity. They are potentially useful as chemically defined vaccine adjuvants, antivirals, and immunostimulatory agents., (Copyright © 2016, American Society for Microbiology. All Rights Reserved.)
- Published
- 2015
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.