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Article ; Online: DDX3X structural analysis: Implications in the pharmacology and innate immunity.

De Colibus, Luigi / Stunnenberg, Melissa / Geijtenbeek, Teunis B H

Current research in immunology

2022 Volume 3, Page(s) 100–109

Abstract: The human DEAD-Box Helicase 3 X-Linked (DDX3X) is an ATP-dependent RNA helicase involved in virtually every step of RNA metabolism, ranging from transcription regulation in the nucleus to translation initiation and stress granule (SG) formation, and ... ...

Abstract	The human DEAD-Box Helicase 3 X-Linked (DDX3X) is an ATP-dependent RNA helicase involved in virtually every step of RNA metabolism, ranging from transcription regulation in the nucleus to translation initiation and stress granule (SG) formation, and plays crucial roles in innate immunity, as well as tumorigenesis and viral infections. This review discusses latest advances in DDX3X biology and structure-function relationship, including the implications of the recent DDX3X crystal structure in complex with double stranded RNA for RNA metabolism, DDX3X involvement in the cross-talk between innate immune responses and cell stress adaptation, and the roles of DDX3X in controlling cell fate.
Language	English
Publishing date	2022-05-24
Publishing country	Netherlands
Document type	Journal Article ; Review
ISSN	2590-2555
ISSN (online)	2590-2555
DOI	10.1016/j.crimmu.2022.05.002
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Article ; Online: Dengue Virus Infects Human Skin Langerhans Cells through Langerin for Dissemination to Dendritic Cells.

Helgers, Leanne C / Keijzer, Nadia C H / van Hamme, John L / Sprokholt, Joris K / Geijtenbeek, Teunis B H

The Journal of investigative dermatology

2023 Volume 144, Issue 5, Page(s) 1099–1111.e3

Abstract: Dengue virus (DENV) is the most disease-causative flavivirus worldwide. DENV as a mosquito-borne virus infects human hosts through the skin; however, the initial target cells in the skin remain unclear. In this study, we have investigated whether ... ...

Abstract	Dengue virus (DENV) is the most disease-causative flavivirus worldwide. DENV as a mosquito-borne virus infects human hosts through the skin; however, the initial target cells in the skin remain unclear. In this study, we have investigated whether epidermal Langerhans cells (LCs) play a role in DENV acquisition and dissemination. We have used a human epidermal ex vivo infection model as well as isolated LCs to investigate infection by DENV. Notably, both immature and mature LCs were permissive to DENV infection in vitro and ex vivo, and infection was dependent on C-type lectin receptor langerin because blocking antibodies against langerin significantly reduced DENV infection in vitro and ex vivo. DENV-infected LCs efficiently transmitted DENV to target cells such as dendritic cells. Moreover, DENV exposure increased the migration of LCs from epidermal explants. These results strongly suggest that DENV targets epidermal LCs for infection and dissemination in the human host. These findings could provide potential drug targets to combat the early stage of DENV infection.
MeSH term(s)	Humans ; Langerhans Cells/virology ; Langerhans Cells/immunology ; Lectins, C-Type/metabolism ; Dengue Virus/physiology ; Mannose-Binding Lectins/metabolism ; Dendritic Cells/virology ; Dendritic Cells/immunology ; Antigens, CD/metabolism ; Dengue/virology ; Dengue/immunology ; Cell Movement ; Cells, Cultured ; Skin/virology ; Skin/pathology ; Epidermis/virology ; Epidermis/pathology ; Epidermis/metabolism
Chemical Substances	Lectins, C-Type ; Mannose-Binding Lectins ; CD207 protein, human ; Antigens, CD
Language	English
Publishing date	2023-11-17
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	80136-7
ISSN	1523-1747 ; 0022-202X
ISSN (online)	1523-1747
ISSN	0022-202X
DOI	10.1016/j.jid.2023.09.287
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Article ; Online: Negative and Positive Selection Pressure During Sexual Transmission of Transmitted Founder HIV-1.

Nijmeijer, Bernadien M / Geijtenbeek, Teunis B H

Frontiers in immunology

2019 Volume 10, Page(s) 1599

Abstract: Sexual transmission of HIV-1 consists of processes that exert either positive or negative selection pressure on the virus. The sum of these selection pressures lead to the transmission of only one specific HIV-1 strain, termed the transmitted founder ... ...

Abstract	Sexual transmission of HIV-1 consists of processes that exert either positive or negative selection pressure on the virus. The sum of these selection pressures lead to the transmission of only one specific HIV-1 strain, termed the transmitted founder virus. Different dendritic cell subsets are abundantly present at mucosal sites and, interestingly, these DC subsets exert opposite pressure on viral selection during sexual transmission. In this review we describe receptors and cellular compartments in DCs that are involved in HIV-1 communication leading to either viral restriction by the host or further dissemination to establish a long-lived reservoir. We discuss the current understanding of host antiretroviral restriction factors against HIV-1 and specifically against the HIV-1 transmitted founder virus. We will also discuss potential clinical implications for exploiting these intrinsic restriction factors in developing novel therapeutic targets. A better understanding of these processes might help in developing strategies against HIV-1 infections by targeting dendritic cells.
MeSH term(s)	Dendritic Cells/immunology ; Disease Transmission, Infectious ; HIV Infections/virology ; HIV-1/physiology ; Host-Pathogen Interactions ; Humans ; Sex
Language	English
Publishing date	2019-07-10
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2019.01599
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Article ; Online: Retinoic acid-loaded liposomes induce human mucosal CD103

Nagy, Noémi Anna / Hafkamp, Florianne M J / Sparrius, Rinske / Bas, Rico / Lozano Vigario, Fernando / van Capel, Toni M M / van Ree, Ronald / Geijtenbeek, Teunis B H / Slütter, Bram / Tas, Sander W / de Jong, Esther C

European journal of immunology

2024 , Page(s) e2350839

Abstract: The active vitamin A metabolite, all-trans-retinoic acid (RA), primes precursor dendritic cells (DCs) into a mucosal phenotype with tolerogenic properties characterized by the expression of integrin CD103. ... ...

Abstract	The active vitamin A metabolite, all-trans-retinoic acid (RA), primes precursor dendritic cells (DCs) into a mucosal phenotype with tolerogenic properties characterized by the expression of integrin CD103. CD103
Language	English
Publishing date	2024-03-02
Publishing country	Germany
Document type	Journal Article
ZDB-ID	120108-6
ISSN	1521-4141 ; 0014-2980
ISSN (online)	1521-4141
ISSN	0014-2980
DOI	10.1002/eji.202350839
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Article ; Online: Mucosal Dendritic Cell Subsets Control HIV-1's Viral Fitness.

Nijmeijer, Bernadien M / Langedijk, Catharina J M / Geijtenbeek, Teunis B H

Annual review of virology

2020 Volume 7, Issue 1, Page(s) 385–402

Abstract: Dendritic cell (DC) subsets are abundantly present in genital and intestinal mucosal tissue and are among the first innate immune cells that encounter human immunodeficiency virus type 1 (HIV-1) after sexual contact. Although DCs have specific ... ...

Abstract	Dendritic cell (DC) subsets are abundantly present in genital and intestinal mucosal tissue and are among the first innate immune cells that encounter human immunodeficiency virus type 1 (HIV-1) after sexual contact. Although DCs have specific characteristics that greatly enhance HIV-1 transmission, it is becoming evident that most DC subsets also have virus restriction mechanisms that exert selective pressure on the viruses during sexual transmission. In this review we discuss the current concepts of the immediate events following viral exposure at genital mucosal sites that lead to selection of specific HIV-1 variants called transmitted founder (TF) viruses. We highlight the importance of the TF HIV-1 phenotype and the role of different DC subsets in establishing infection. Understanding the biology of HIV-1 transmission will contribute to the design of novel treatment strategies preventing HIV-1 dissemination.
MeSH term(s)	Dendritic Cells/classification ; Dendritic Cells/immunology ; Dendritic Cells/virology ; HIV Infections/immunology ; HIV Infections/prevention & control ; HIV Infections/virology ; HIV-1/immunology ; Humans ; Mucous Membrane/cytology ; Mucous Membrane/immunology ; Reproductive Tract Infections/immunology ; Reproductive Tract Infections/virology ; Skin/cytology ; Skin/immunology ; Skin/virology
Language	English
Publishing date	2020-09-29
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2764224-0
ISSN	2327-0578 ; 2327-056X
ISSN (online)	2327-0578
ISSN	2327-056X
DOI	10.1146/annurev-virology-020520-025625
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Article: Variations in the Abortive HIV-1 RNA Hairpin Do Not Impede Viral Sensing and Innate Immune Responses.

Stunnenberg, Melissa / van Hamme, John L / Das, Atze T / Berkhout, Ben / Geijtenbeek, Teunis B H

Pathogens (Basel, Switzerland)

2021 Volume 10, Issue 7

Abstract: The highly conserved trans-acting response element (TAR) present in the RNA genome of human immunodeficiency virus 1 (HIV-1) is a stably folded hairpin structure involved in viral replication. However, TAR is also sensed by viral sensors, leading to ... ...

Abstract	The highly conserved trans-acting response element (TAR) present in the RNA genome of human immunodeficiency virus 1 (HIV-1) is a stably folded hairpin structure involved in viral replication. However, TAR is also sensed by viral sensors, leading to antiviral immunity. While high variation in the TAR RNA structure renders the virus replication-incompetent, effects on viral sensing remain unclear. Here, we investigated the role of TAR RNA structure and stability on viral sensing. TAR mutants with deletions in the TAR hairpin that enhanced thermodynamic stability increased antiviral responses. Strikingly, TAR mutants with lower stability due to destabilization of the TAR hairpin also increased antiviral responses without affecting pro-inflammatory responses. Moreover, mutations that affected the TAR RNA sequence also enhanced specific antiviral responses. Our data suggest that mutations in TAR of replication-incompetent viruses can still induce immune responses via viral sensors, hereby underscoring the robustness of HIV-1 RNA sensing mechanisms.
Language	English
Publishing date	2021-07-15
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2695572-6
ISSN	2076-0817
ISSN	2076-0817
DOI	10.3390/pathogens10070897
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Article ; Online: Abortive HIV-1 RNA induces pro-IL-1β maturation via protein kinase PKR and inflammasome activation in humans.

Stunnenberg, Melissa / van Hamme, John L / Trimp, Marjolein / Gringhuis, Sonja I / Geijtenbeek, Teunis B H

European journal of immunology

2021 Volume 51, Issue 10, Page(s) 2464–2477

Abstract: The proinflammatory cytokine IL-1β mediates high levels of immune activation observed during acute and chronic human immunodeficiency virus 1 (HIV-1) infection. Little is known about the mechanisms that drive IL-1β activation during HIV-1 infection. Here, ...

Abstract	The proinflammatory cytokine IL-1β mediates high levels of immune activation observed during acute and chronic human immunodeficiency virus 1 (HIV-1) infection. Little is known about the mechanisms that drive IL-1β activation during HIV-1 infection. Here, we have identified a crucial role for abortive HIV-1 RNAs in inducing IL-1β in humans. Abortive HIV-1 RNAs were sensed by protein kinase RNA-activated (PKR), which triggered activation of the canonical NLRP3 inflammasome and caspase-1, leading to pro-IL-1β processing and secretion. PKR activated the inflammasome via ROS generation and MAP kinases ERK1/2, JNK, and p38. Inhibition of PKR during HIV-1 infection blocked IL-1β production. As abortive HIV-1 RNAs are produced during productive infection and latency, our data strongly suggest that targeting PKR signaling might attenuate immune activation during acute and chronic HIV-1 infection.
MeSH term(s)	HIV Infections/metabolism ; HIV Infections/virology ; HIV-1/physiology ; Host-Pathogen Interactions ; Humans ; Inflammasomes/metabolism ; Interleukin-1beta/metabolism ; MAP Kinase Signaling System ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism ; RNA, Viral/genetics ; RNA, Viral/metabolism ; Reactive Oxygen Species/metabolism ; Receptors, Pattern Recognition/metabolism ; Signal Transduction ; eIF-2 Kinase/metabolism
Chemical Substances	IL1B protein, human ; Inflammasomes ; Interleukin-1beta ; NLR Family, Pyrin Domain-Containing 3 Protein ; RNA, Viral ; Reactive Oxygen Species ; Receptors, Pattern Recognition ; EIF2AK2 protein, human (EC 2.7.11.1) ; eIF-2 Kinase (EC 2.7.11.1)
Language	English
Publishing date	2021-07-23
Publishing country	Germany
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	120108-6
ISSN	1521-4141 ; 0014-2980
ISSN (online)	1521-4141
ISSN	0014-2980
DOI	10.1002/eji.202149275
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Zs.A 489: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MG 85: Show issues

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Article ; Online: DDX3 in HIV-1 infection and sensing: A paradox.

Stunnenberg, Melissa / Geijtenbeek, Teunis B H / Gringhuis, Sonja I

Cytokine & growth factor reviews

2018 Volume 40, Page(s) 32–39

Abstract: HIV-1 sensors and their signaling features have been an ongoing topic of intense research over the last decade, as these mechanisms fail to establish protective immunity against HIV-1. Here, we discuss how HIV-1 infects dendritic cells (DCs) and which ... ...

Abstract	HIV-1 sensors and their signaling features have been an ongoing topic of intense research over the last decade, as these mechanisms fail to establish protective immunity against HIV-1. Here, we discuss how HIV-1 infects dendritic cells (DCs) and which sensors play a role in recognizing viral DNA and RNA in these specialized immune cells. We will elaborate on the RNA helicase DDX3, which is crucial in translation initiation of HIV-1 mRNA, but also fulfills an important role as RNA sensor and inducer of antiviral immunity in DCs. As DDX3 is indispensable for HIV-1 replication, the virus cannot escape sensing by DDX3, which is an important aspect of its function. Last but not least, we will discuss how HIV-1 suppresses DDX3 sensing and how this impacts the viral load in HIV-1-infected individuals.
MeSH term(s)	Adaptor Proteins, Signal Transducing/metabolism ; Cell Adhesion Molecules/metabolism ; Cell Cycle Proteins/metabolism ; DEAD-box RNA Helicases/immunology ; DEAD-box RNA Helicases/metabolism ; DNA, Viral/immunology ; Dendritic Cells/immunology ; Dendritic Cells/virology ; HIV Infections/immunology ; HIV-1/immunology ; Host-Pathogen Interactions/immunology ; Humans ; Lectins, C-Type/metabolism ; Peptide Chain Initiation, Translational/physiology ; Protein Serine-Threonine Kinases/metabolism ; Proto-Oncogene Proteins/metabolism ; RNA, Viral/immunology ; Receptors, Cell Surface/metabolism ; Viral Load ; Virus Replication/physiology ; Polo-Like Kinase 1
Chemical Substances	Adaptor Proteins, Signal Transducing ; Cell Adhesion Molecules ; Cell Cycle Proteins ; DC-specific ICAM-3 grabbing nonintegrin ; DNA, Viral ; Lectins, C-Type ; MAVS protein, human ; Proto-Oncogene Proteins ; RNA, Viral ; Receptors, Cell Surface ; Protein Serine-Threonine Kinases (EC 2.7.11.1) ; DDX3X protein, human (EC 3.6.1.-) ; DEAD-box RNA Helicases (EC 3.6.4.13)
Language	English
Publishing date	2018-03-08
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	1330534-7
ISSN	1879-0305 ; 1359-6101
ISSN (online)	1879-0305
ISSN	1359-6101
DOI	10.1016/j.cytogfr.2018.03.001
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Zs.A 2653: Show issues

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ab Jg. 2022: Lesesaal (EG)

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Article ; Online: Crosstalk between R848 and abortive HIV-1 RNA-induced signaling enhances antiviral immunity.

Stunnenberg, Melissa / van Hamme, John L / Zijlstra-Willems, Esther M / Gringhuis, Sonja I / Geijtenbeek, Teunis B H

Journal of leukocyte biology

2022 Volume 112, Issue 2, Page(s) 289–298

Abstract: Pathogens trigger multiple pattern recognition receptors (PRRs) that together dictate innate and adaptive immune responses. Understanding the crosstalk between PRRs is important to enhance vaccine efficacy. Abortive HIV-1 RNA transcripts are produced ... ...

Abstract	Pathogens trigger multiple pattern recognition receptors (PRRs) that together dictate innate and adaptive immune responses. Understanding the crosstalk between PRRs is important to enhance vaccine efficacy. Abortive HIV-1 RNA transcripts are produced during acute and chronic HIV-1 infection and are known ligands for different PRRs, leading to antiviral and proinflammatory responses. Here, we have investigated the crosstalk between responses induced by these 58 nucleotide-long HIV-1 RNA transcripts and different TLR ligands. Costimulation of dendritic cells (DCs) with abortive HIV-1 RNA and TLR7/8 agonist R848, but not other TLR agonists, resulted in enhanced antiviral type I IFN responses as well as adaptive immune responses via the induction of DC-mediated T helper 1 (T
MeSH term(s)	Adjuvants, Immunologic ; Antiviral Agents ; CD8-Positive T-Lymphocytes ; Dendritic Cells ; HIV-1/physiology ; Immunity, Innate ; RNA ; Receptors, Pattern Recognition
Chemical Substances	Adjuvants, Immunologic ; Antiviral Agents ; Receptors, Pattern Recognition ; RNA (63231-63-0)
Language	English
Publishing date	2022-01-04
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	605722-6
ISSN	1938-3673 ; 0741-5400
ISSN (online)	1938-3673
ISSN	0741-5400
DOI	10.1002/JLB.4A0721-365R
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Zs.A 603: Show issues

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Je nach Verfügbarkeit (siehe Angabe bei Bestand)
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Article ; Online: Human Dendritic Cells Transmit Enterovirus A71 via Heparan Sulfates to Target Cells Independent of Viral Replication.

Helgers, Leanne C / Bhoekhan, Michel S / Pajkrt, Dasja / Wolthers, Katja C / Geijtenbeek, Teunis B H / Sridhar, Adithya

Microbiology spectrum

2022 , Page(s) e0282222

Abstract: Enterovirus A71 (EV-A71) is a causative agent of life-threatening neurological diseases in young children. EV-A71 is highly infectious but it remains unclear how the virus disseminates from primary entry sites-the mucosa of the respiratory tract or the ... ...

Abstract	Enterovirus A71 (EV-A71) is a causative agent of life-threatening neurological diseases in young children. EV-A71 is highly infectious but it remains unclear how the virus disseminates from primary entry sites-the mucosa of the respiratory tract or the intestine-to secondary replication sites-skin or brain. Here, we investigated the role of dendritic cells (DCs) in EV-A71 dissemination. DCs reside in the mucosa of the airway and gut, and migrate to lymphoid tissues upon activation and, therefore, could facilitate EV-A71 dissemination to secondary replication sites. Monocyte-derived DCs were not permissive to different genotypes of EV-A71 but, notably, coculture with EV-A71-susceptiblle RD99 cells led to very efficient infection of RD99 cells. Notably, EV-A71 transmission of DCs to RD99 was independent of viral replication as a replication inhibitor did not affect transmission. Soluble heparin blocked EV-A71 transmission by DCs to RD99 cells, in contrast to antibodies against known attachment receptor DC-SIGN. These results strongly suggest that DCs might be a first target for EV-A71 and involved in viral dissemination via heparan sulfates and heparin derivatives might be an effective treatment to attenuate dissemination.
Language	English
Publishing date	2022-10-12
Publishing country	United States
Document type	Journal Article
ZDB-ID	2807133-5
ISSN	2165-0497 ; 2165-0497
ISSN (online)	2165-0497
ISSN	2165-0497
DOI	10.1128/spectrum.02822-22
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