15 results on '"Yoh, Sunnie"'
Search Results
2. Sec61 Inhibitor Apratoxin S4 Potently Inhibits SARS-CoV‑2 and Exhibits Broad-Spectrum Antiviral Activity.
- Author
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Pohl, Marie O., Martin-Sancho, Laura, Ratnayake, Ranjala, White, Kris M., Riva, Laura, Chen, Qi-Yin, Lieber, Gauthier, Busnadiego, Idoia, Yin, Xin, Lin, Samuel, Pu, Yuan, Pache, Lars, Rosales, Romel, Déjosez, Marion, Qin, Yiren, De Jesus, Paul D., Beall, Anne, Yoh, Sunnie, Hale, Benjamin G., and Zwaka, Thomas P.
- Published
- 2022
- Full Text
- View/download PDF
3. Sensor Sensibility—HIV-1 and the Innate Immune Response.
- Author
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Xin Yin, Langer, Simon, Zeli Zhang, Herbert, Kristina M., Yoh, Sunnie, König, Renate, and Chanda, Sumit K.
- Subjects
IMMUNE response ,PATTERN perception receptors ,MOLECULAR recognition ,NATURAL immunity ,HIV ,VACCINE effectiveness - Abstract
Innate immunity represents the human immune system’s first line of defense against a pathogenic intruder and is initiated by the recognition of conserved molecular structures known as pathogen-associated molecular patterns (PAMPs) by specialized cellular sensors, called pattern recognition receptors (PRRs). Human immunodeficiency virus type 1 (HIV-1) is a unique human RNA virus that causes acquired immunodeficiency syndrome (AIDS) in infected individuals. During the replication cycle, HIV-1 undergoes reverse transcription of its RNA genome and integrates the resulting DNA into the human genome. Subsequently, transcription of the integrated provirus results in production of new virions and spreading infection of the virus. Throughout the viral replication cycle, numerous nucleic acid derived PAMPs can be recognized by a diverse set of innate immune sensors in infected cells. However, HIV-1 has evolved effcient strategies to evade or counteract this immune surveillance and the downstream responses. Understanding the molecular underpinnings of the concerted actions of the innate immune system, as well as the corresponding viral evasion mechanisms during infection, is critical to understanding HIV-1 transmission and pathogenesis, and may provide important guidance for the design of appropriate adjuvant and vaccine strategies. Here, we summarize current knowledge of the molecular basis for sensing HIV-1 in human cells, including CD4
+ T cells, dendritic cells, and macrophages. Furthermore, we discuss the underlying mechanisms by which innate sensing is regulated, and describe the strategies developed by HIV-1 to evade sensing and immune responses. [ABSTRACT FROM AUTHOR]- Published
- 2020
- Full Text
- View/download PDF
4. The Iws1:Spt6:CTD complex controls cotranscriptional mRNA biosynthesis and HYPB/Setd2-mediated histone H3K36 methylation
- Author
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Yoh, Sunnie M., Lucas, Joseph S., and Jones, Katherine A.
- Subjects
Gene expression -- Analysis ,RNA polymerases -- Research ,Histones -- Chemical properties ,Biological sciences - Published
- 2008
5. NLRX1 Sequesters STING to Negatively Regulate the Interferon Response, Thereby Facilitating the Replication of HIV-1 and DNA Viruses.
- Author
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Guo, Haitao, König, Renate, Deng, Meng, Riess, Maximilian, Mo, Jinyao, Zhang, Lu, Petrucelli, Alex, Yoh, Sunnie M., Barefoot, Brice, Samo, Melissa, Sempowski, Gregory D., Zhang, Aiping, Colberg-Poley, Anamaris M., Feng, Hui, Lemon, Stanley M., Liu, Yong, Zhang, Yanping, Wen, Haitao, Zhang, Zhigang, and Damania, Blossom
- Abstract
Summary Understanding the negative regulators of antiviral immune responses will be critical for advancing immune-modulated antiviral strategies. NLRX1, an NLR protein that negatively regulates innate immunity, was previously identified in an unbiased siRNA screen as required for HIV infection. We find that NLRX1 depletion results in impaired nuclear import of HIV-1 DNA in human monocytic cells. Additionally, NLRX1 was observed to reduce type-I interferon (IFN-I) and cytokines in response to HIV-1 reverse-transcribed DNA. NLRX1 sequesters the DNA-sensing adaptor STING from interaction with TANK-binding kinase 1 (TBK1), which is a requisite for IFN-1 induction in response to DNA. NLRX1-deficient cells generate an amplified STING-dependent host response to cytosolic DNA, c-di-GMP, cGAMP, HIV-1, and DNA viruses. Accordingly, Nlrx1 −/− mice infected with DNA viruses exhibit enhanced innate immunity and reduced viral load. Thus, NLRX1 is a negative regulator of the host innate immune response to HIV-1 and DNA viruses. [ABSTRACT FROM AUTHOR]
- Published
- 2016
- Full Text
- View/download PDF
6. Recognition of HIV-1 capsid by PQBP1 licenses an innate immune sensing of nascent HIV-1 DNA.
- Author
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Yoh, Sunnie M., Mamede, João I., Lau, Derrick, Ahn, Narae, Sánchez-Aparicio, Maria T., Temple, Joshua, Tuckwell, Andrew, Fuchs, Nina V., Cianci, Gianguido C., Riva, Laura, Curry, Heather, Yin, Xin, Gambut, Stéphanie, Simons, Lacy M., Hultquist, Judd F., König, Renate, Xiong, Yong, García-Sastre, Adolfo, Böcking, Till, and Hope, Thomas J.
- Subjects
- *
HIV , *DNA synthesis , *RETROVIRUS diseases , *DNA , *MULTI-factor authentication , *GLUTAMINE synthetase - Abstract
We have previously described polyglutamine-binding protein 1 (PQBP1) as an adapter required for the cyclic GMP-AMP synthase (cGAS)-mediated innate response to the human immunodeficiency virus 1 (HIV-1) and other lentiviruses. Cytoplasmic HIV-1 DNA is a transient and low-abundance pathogen-associated molecular pattern (PAMP), and the mechanism for its detection and verification is not fully understood. Here, we show a two-factor authentication strategy by the innate surveillance machinery to selectively respond to the low concentration of HIV-1 DNA, while distinguishing these species from extranuclear DNA molecules. We find that, upon HIV-1 infection, PQBP1 decorates the intact viral capsid, and this serves as a primary verification step for the viral nucleic acid cargo. As reverse transcription and capsid disassembly initiate, cGAS is recruited to the capsid in a PQBP1-dependent manner. This positions cGAS at the site of PAMP generation and sanctions its response to a low-abundance DNA PAMP. [Display omitted] • PQBP1 binding to incoming HIV-1 capsids initiates the innate sensing • PQBP1 recruits cGAS once capsid disassembly and DNA synthesis are initiated • PQBP1-cGAS assembly on the capsid sanctions innate sensing of HIV DNA Yoh and Mamede et al. demonstrate a two-step authentication system in response to retroviral infection. The work reveals a strategy by host immune surveillance to broaden its pathogen repertoire while limiting deleterious responses to host DNAs. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
7. PQBP1 Is a Proximal Sensor of the cGAS-Dependent Innate Response to HIV-1.
- Author
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Yoh, Sunnie M., Schneider, Monika, Seifried, Janna, Soonthornvacharin, Stephen, Akleh, Rana E., Olivieri, Kevin C., De Jesus, Paul D., Ruan, Chunhai, de Castro, Elisa, Ruiz, Pedro A., Germanaud, David, des Portes, Vincent, García-Sastre, Adolfo, König, Renate, and Chanda, Sumit K.
- Subjects
- *
POLYGLUTAMINE , *CARRIER proteins , *DENDRITIC cells , *BIOSENSORS , *HIV infections -- Immunological aspects , *ANTIVIRAL agents , *PHYSIOLOGY - Abstract
Summary Dendritic cells (DCs) play a critical role in the immune response to viral infection through the facilitation of cell-intrinsic antiviral activity and the activation of adaptive immunity. HIV-1 infection of DCs triggers an IRF3-dependent innate immune response, which requires the activity of cyclic GAMP synthase (cGAS). We report the results of a targeted RNAi screen utilizing primary human monocyte-derived DCs (MDDCs) to identify immune regulators that directly interface with HIV-1-encoded features to initiate this innate response. Polyglutamine binding protein 1 (PQBP1) emerged as a strong candidate through this analysis. We found that PQBP1 directly binds to reverse-transcribed HIV-1 DNA and interacts with cGAS to initiate an IRF3-dependent innate response. MDDCs derived from Renpenning syndrome patients, who harbor mutations in the PQBP1 locus, possess a severely attenuated innate immune response to HIV-1 challenge, underscoring the role of PQBP1 as a proximal innate sensor of a HIV-1 infection. [ABSTRACT FROM AUTHOR]
- Published
- 2015
- Full Text
- View/download PDF
8. Molecular Analysis of Human Resistance to Thyroid Hormone Syndrome.
- Author
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Walker, John M., Baniahmad, Aria, Yoh, Sunnie M., and Privalsky, Martin L.
- Abstract
Resistance to thyroid hormone (RTH) syndrome is an inherited human endocrine disease, which is manifested as a failure to respond properly to elevated circulating thyroid hormone (1-4). RTH syndrome behaves as an autosomal dominant trait, and has been mapped at the molecular level to a diverse array of mutations within the thyroid hormone receptor (TR)-β locus (1-4). As detailed elsewhere in this review series, TRs bind to specific DNA sequences, denoted thyroid hormone response elements (TREs) and regulate transcription of adjacent target genes in response to thyroid hormone (5-7). TRs typically repress transcription in the absence of hormone and activate transcription in the presence of hormone (8-10). These bipolar transcriptional properties of the receptor are mediated by the receptor's ability to recruit ancillary polypeptides, denoted corepressors and coactivators, to the target promoter (11-16). Corepressors and coactivators modulate transcription both by covalent modification of the chromatin template and by direct interactions with components of the general transcriptional machinery. Corepressors are typically recruited by TRs in the absence of hormone, whereas binding of hormone to the TRs results in a release of the corepressors and a recruitment of the coactivator polypeptides (11-16). [ABSTRACT FROM AUTHOR]
- Published
- 2002
- Full Text
- View/download PDF
9. The multi-tasking P-TEFb complex
- Author
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Brès, Vanessa, Yoh, Sunnie M, and Jones, Katherine A
- Subjects
- *
RNA polymerases , *TRANSFERASES , *MESSENGER RNA , *HISTONES , *CYTOPLASM - Abstract
P-TEFb (CycT1:Cdk9), the metazoan RNA polymerase II Ser2 C-terminal domain (CTD) kinase, regulates transcription elongation at many genes and integrates mRNA synthesis with histone modification, pre-mRNA processing, and mRNA export. Recruitment of P-TEFb to target genes requires deubiquitination of H2Bub, phosphorylation of H3S10, and the bromodomain protein, Brd4. Brd4 activates growth-related genes in the G1 phase of the cell cycle and can also tether P-TEFb to mitotic chromosomes, possibly to mark sites of active transcription throughout cell division. P-TEFb co-operates with c-Myc during transactivation and cell transformation, and also requires SKIP (c-Ski-interacting protein), an mRNA elongation and splicing factor. Some functions of the P-TEFb/Ser2P CTD are executed by the Spt6 transcription elongation factor, which binds directly to the phosphorylated CTD and recruits the Iws1 (‘interacts with Spt6’) protein. Iws1, in turn, interacts with the REF1/Aly nuclear export adaptor and stimulates the kinetics of mRNA export. Given the prominent role of Spt6 in regulating chromatin structure, the CTD-bound Spt6:Iws1 complex may also control histone modifications during elongation. Following transcription, P-TEFb accompanies the mature mRNA to the cytoplasm to promote translation elongation. [Copyright &y& Elsevier]
- Published
- 2008
- Full Text
- View/download PDF
10. MDA5 Governs the Innate Immune Response to SARS-CoV-2 in Lung Epithelial Cells.
- Author
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Yin, Xin, Riva, Laura, Pu, Yuan, Martin-Sancho, Laura, Kanamune, Jun, Yamamoto, Yuki, Sakai, Kouji, Gotoh, Shimpei, Miorin, Lisa, De Jesus, Paul D., Yang, Chih-Cheng, Herbert, Kristina M., Yoh, Sunnie, Hultquist, Judd F., García-Sastre, Adolfo, and Chanda, Sumit K.
- Abstract
Recent studies have profiled the innate immune signatures in patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and suggest that cellular responses to viral challenge may affect disease severity. Yet the molecular events that underlie cellular recognition and response to SARS-CoV-2 infection remain to be elucidated. Here, we find that SARS-CoV-2 replication induces a delayed interferon (IFN) response in lung epithelial cells. By screening 16 putative sensors involved in sensing of RNA virus infection, we found that MDA5 and LGP2 primarily regulate IFN induction in response to SARS-CoV-2 infection. Further analyses revealed that viral intermediates specifically activate the IFN response through MDA5-mediated sensing. Additionally, we find that IRF3, IRF5, and NF-κB/p65 are the key transcription factors regulating the IFN response during SARS-CoV-2 infection. In summary, these findings provide critical insights into the molecular basis of the innate immune recognition and signaling response to SARS-CoV-2. • SARS-CoV-2 replication induces a delayed IFN response in lung epithelial cells • MDA5 and LGP2 are the major sensors recognizing SARS-CoV-2 infection • Viral intermediates activate the IFN response through MDA5-mediated sensing • IRF3, IRF5, and NF-κB/p65 are required for the IFN response induced by SARS-CoV-2 The molecular events that underlie innate immune recognition and response to SARS-CoV-2 infection remain unclear. Yin et al. report that SARS-CoV-2 replication induces a delayed interferon (IFN) response that is triggered by sensing of viral RNA through the MDA5 pattern recognition receptor. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
11. The Spt6 SH2 domain binds Ser2-P RNAPII to direct Iws1-dependent mRNA splicing and export.
- Author
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Yoh, Sunnie M., Cho, Helen, Pickle, Loni, Evans, Ronald M., and Jones, Katherine A.
- Subjects
- *
GENES , *HISTONES , *RNA polymerases , *PROTEIN-tyrosine phosphatase , *PROTEINS - Abstract
Spt6 promotes transcription elongation at many genes and functions as a histone H3 chaperone to alter chromatin structure during transcription. We show here that mammalian Spt6 binds Ser2-phosphorylated (Ser2P) RNA polymerase II (RNAPII) through a primitive SH2 domain, which recognizes phosphoserine rather than phosphotyrosine residues. Surprisingly, a point mutation in the Spt6 SH2 domain (R1358K) blocked binding to RNAPIIo without affecting transcription elongation rates in vitro. However, HIV-1 and c-myc RNAs formed in cells expressing the mutant Spt6 protein were longer than normal and contained splicing defects. Ectopic expression of the wild-type, but not mutant, Spt6 SH2 domain, caused bulk poly(A)+ RNAs to be retained in the nucleus, further suggesting a widespread role for Spt6 in mRNA processing or assembly of export-competent mRNP particles. We cloned the human Spt6-interacting protein, hIws1 (interacts with Spt6), and found that it associates with the nuclear RNA export factor, REF1/Aly. Depletion of endogenous hIws1 resulted in mRNA processing defects, lower levels of REF1/Aly at the c-myc gene, and nuclear retention of bulk HeLa poly(A)+ RNAs in vivo. Thus binding of Spt6 to Ser2-P RNAPII provides a cotranscriptional mechanism to recruit Iws1, REF1/Aly, and associated mRNA processing, surveillance, and export factors to responsive genes. [ABSTRACT FROM AUTHOR]
- Published
- 2007
- Full Text
- View/download PDF
12. Sensor Sensibility-HIV-1 and the Innate Immune Response.
- Author
-
Yin X, Langer S, Zhang Z, Herbert KM, Yoh S, König R, and Chanda SK
- Subjects
- HIV Infections immunology, Humans, Interferons metabolism, Signal Transduction, HIV-1 immunology, Immunity, Innate, Pathogen-Associated Molecular Pattern Molecules metabolism
- Abstract
Innate immunity represents the human immune system's first line of defense against a pathogenic intruder and is initiated by the recognition of conserved molecular structures known as pathogen-associated molecular patterns (PAMPs) by specialized cellular sensors, called pattern recognition receptors (PRRs). Human immunodeficiency virus type 1 (HIV-1) is a unique human RNA virus that causes acquired immunodeficiency syndrome (AIDS) in infected individuals. During the replication cycle, HIV-1 undergoes reverse transcription of its RNA genome and integrates the resulting DNA into the human genome. Subsequently, transcription of the integrated provirus results in production of new virions and spreading infection of the virus. Throughout the viral replication cycle, numerous nucleic acid derived PAMPs can be recognized by a diverse set of innate immune sensors in infected cells. However, HIV-1 has evolved efficient strategies to evade or counteract this immune surveillance and the downstream responses. Understanding the molecular underpinnings of the concerted actions of the innate immune system, as well as the corresponding viral evasion mechanisms during infection, is critical to understanding HIV-1 transmission and pathogenesis, and may provide important guidance for the design of appropriate adjuvant and vaccine strategies. Here, we summarize current knowledge of the molecular basis for sensing HIV-1 in human cells, including CD4
+ T cells, dendritic cells, and macrophages. Furthermore, we discuss the underlying mechanisms by which innate sensing is regulated, and describe the strategies developed by HIV-1 to evade sensing and immune responses.- Published
- 2020
- Full Text
- View/download PDF
13. Large-Scale Arrayed Analysis of Protein Degradation Reveals Cellular Targets for HIV-1 Vpu.
- Author
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Jain P, Boso G, Langer S, Soonthornvacharin S, De Jesus PD, Nguyen Q, Olivieri KC, Portillo AJ, Yoh SM, Pache L, and Chanda SK
- Subjects
- Antiviral Agents metabolism, Down-Regulation, HEK293 Cells, HeLa Cells, Humans, Interferons metabolism, Proteasome Endopeptidase Complex metabolism, Protein Stability, Reproducibility of Results, Virion metabolism, HIV-1 metabolism, Human Immunodeficiency Virus Proteins metabolism, Proteolysis, Viral Regulatory and Accessory Proteins metabolism
- Abstract
Accessory proteins of lentiviruses, such as HIV-1, target cellular restriction factors to enhance viral replication. Systematic analyses of proteins that are targeted for degradation by HIV-1 accessory proteins may provide a better understanding of viral immune evasion strategies. Here, we describe a high-throughput platform developed to study cellular protein stability in a highly parallelized matrix format. We used this approach to identify cellular targets of the HIV-1 accessory protein Vpu through arrayed coexpression with 433 interferon-stimulated genes, followed by differential fluorescent labeling and automated image analysis. Among the previously unreported Vpu targets identified by this approach, we find that the E2 ligase mediating ISG15 conjugation, UBE2L6, and the transmembrane protein PLP2 are targeted by Vpu during HIV-1 infection to facilitate late-stage replication. This study provides a framework for the systematic and high-throughput evaluation of protein stability and establishes a more comprehensive portrait of cellular Vpu targets., (Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.)
- Published
- 2018
- Full Text
- View/download PDF
14. Systems-based analysis of RIG-I-dependent signalling identifies KHSRP as an inhibitor of RIG-I receptor activation.
- Author
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Soonthornvacharin S, Rodriguez-Frandsen A, Zhou Y, Galvez F, Huffmaster NJ, Tripathi S, Balasubramaniam VR, Inoue A, de Castro E, Moulton H, Stein DA, Sánchez-Aparicio MT, De Jesus PD, Nguyen Q, König R, Krogan NJ, García-Sastre A, Yoh SM, and Chanda SK
- Subjects
- HEK293 Cells, Humans, Immunity, Innate, Influenza A Virus, H1N1 Subtype immunology, Protein Binding, Protein Interaction Mapping, Protein Interaction Maps, Receptors, Immunologic, DEAD Box Protein 58 antagonists & inhibitors, RNA, Viral immunology, RNA-Binding Proteins metabolism, Signal Transduction, Trans-Activators metabolism
- Abstract
Retinoic acid-inducible gene I (RIG-I) receptor recognizes 5'-triphosphorylated RNA and triggers a signalling cascade that results in the induction of type-I interferon (IFN)-dependent responses. Its precise regulation represents a pivotal balance between antiviral defences and autoimmunity. To elucidate the cellular cofactors that regulate RIG-I signalling, we performed two global RNA interference analyses to identify both positive and negative regulatory nodes operating on the signalling pathway during virus infection. These factors were integrated with experimentally and computationally derived interactome data to build a RIG-I protein interaction network. Our analysis revealed diverse cellular processes, including the unfolded protein response, Wnt signalling and RNA metabolism, as critical cellular components governing innate responses to non-self RNA species. Importantly, we identified K-Homology Splicing Regulatory Protein (KHSRP) as a negative regulator of this pathway. We find that KHSRP associates with the regulatory domain of RIG-I to maintain the receptor in an inactive state and attenuate its sensing of viral RNA (vRNA). Consistent with increased RIG-I antiviral signalling in the absence of KHSRP, viral replication is reduced when KHSRP expression is knocked down both in vitro and in vivo. Taken together, these data indicate that KHSRP functions as a checkpoint regulator of the innate immune response to pathogen challenge.
- Published
- 2017
- Full Text
- View/download PDF
15. Molecular analysis of human resistance to thyroid hormone syndrome.
- Author
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Yoh SM and Privalsky ML
- Subjects
- Humans, Receptors, Thyroid Hormone physiology, Thyroid Hormone Receptors beta, Receptors, Thyroid Hormone genetics, Thyroid Hormone Resistance Syndrome genetics
- Published
- 2002
- Full Text
- View/download PDF
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