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Article ; Online: A Pocket Guide to CCR5-Neurotropic Flavivirus Edition.

Garg, Amit / Lim, Jean K

2023 Volume 16, Issue 1

Abstract: CCR5 is among the most studied chemokine receptors due to its profound significance in human health and disease. The notion that CCR5 is a functionally redundant receptor was challenged through the demonstration of its unique protective role in the ... ...

Abstract	CCR5 is among the most studied chemokine receptors due to its profound significance in human health and disease. The notion that CCR5 is a functionally redundant receptor was challenged through the demonstration of its unique protective role in the context of West Nile virus in both mice and humans. In the nearly two decades since this initial discovery, numerous studies have investigated the role of CCR5 in the context of other medically important neurotropic flaviviruses, most of which appear to support a broad neuroprotective role for this receptor, although how CCR5 exerts its protective effect has been remarkably varied. In this review, we summarize the mechanisms by which CCR5 controls neurotropic flaviviruses, as well as results from human studies evaluating a genetic link to CCR5, and propose unexplored areas of research that are needed to unveil even more exciting roles for this important receptor.
MeSH term(s)	Humans ; Animals ; Mice ; Flavivirus ; West Nile virus/genetics ; Receptors, Chemokine ; Receptors, CCR5/genetics
Chemical Substances	Receptors, Chemokine ; CCR5 protein, human ; Receptors, CCR5
Language	English
Publishing date	2023-12-23
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2516098-9
ISSN	1999-4915 ; 1999-4915
ISSN (online)	1999-4915
ISSN	1999-4915
DOI	10.3390/v16010028
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Dengue and Zika: The Complexities of Being Related.

Krammer, Florian / Lim, Jean K

Trends in immunology

2019 Volume 40, Issue 6, Page(s) 467–469

Abstract: Following the recent Zika virus (ZIKV) outbreak in the Americas, a major question that has arisen is how dengue virus (DENV) immunity impacts Zika virus infection and disease. A recent study (Rodriguez-Barraquer, I. et al. Science 2019;363:607-610) shows ...

Abstract	Following the recent Zika virus (ZIKV) outbreak in the Americas, a major question that has arisen is how dengue virus (DENV) immunity impacts Zika virus infection and disease. A recent study (Rodriguez-Barraquer, I. et al. Science 2019;363:607-610) shows that DENV immunity is, for the most part, protective against ZIKV, but exceptions may exist.
MeSH term(s)	Dengue ; Dengue Virus ; Humans ; Zika Virus ; Zika Virus Infection
Language	English
Publishing date	2019-05-06
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Comment
ZDB-ID	2036831-8
ISSN	1471-4981 ; 1471-4906
ISSN (online)	1471-4981
ISSN	1471-4906
DOI	10.1016/j.it.2019.04.008
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Zs.A 1601: 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)
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Article ; Online: GPER1 is required to protect fetal health from maternal inflammation.

Harding, Alfred T / Goff, Marisa A / Froggatt, Heather M / Lim, Jean K / Heaton, Nicholas S

Science (New York, N.Y.)

2021 Volume 371, Issue 6526, Page(s) 271–276

Abstract: Type I interferon (IFN) signaling in fetal tissues causes developmental abnormalities and fetal demise. Although pathogens that infect fetal tissues can induce birth defects through the local production of type I IFN, it remains unknown why systemic IFN ... ...

Abstract	Type I interferon (IFN) signaling in fetal tissues causes developmental abnormalities and fetal demise. Although pathogens that infect fetal tissues can induce birth defects through the local production of type I IFN, it remains unknown why systemic IFN generated during maternal infections only rarely causes fetal developmental defects. Here, we report that activation of the guanine nucleotide-binding protein-coupled estrogen receptor 1 (GPER1) during pregnancy is both necessary and sufficient to suppress IFN signaling and does so disproportionately in reproductive and fetal tissues. Inactivation of GPER1 in mice halted fetal development and promoted fetal demise, but only in the context of maternal inflammation. Thus, GPER1 is a central regulator of IFN signaling during pregnancy that allows dynamic antiviral responses in maternal tissues while also preserving fetal health.
MeSH term(s)	Animals ; Benzodioxoles/pharmacology ; CRISPR-Cas Systems ; Female ; Fetal Diseases/immunology ; Fetal Diseases/virology ; Fetus/immunology ; Fetus/virology ; Humans ; Inflammation/immunology ; Influenza A virus/immunology ; Influenza, Human/immunology ; Interferon Type I/immunology ; Maternal-Fetal Exchange/immunology ; Mice ; Mice, Inbred C57BL ; Placenta/immunology ; Placenta/virology ; Pregnancy ; Pregnancy Complications, Infectious/immunology ; Quinolines/pharmacology ; Receptors, Estrogen/antagonists & inhibitors ; Receptors, Estrogen/metabolism ; Receptors, G-Protein-Coupled/antagonists & inhibitors ; Receptors, G-Protein-Coupled/metabolism
Chemical Substances	4-(6-bromo-1,3-benzodioxol-5-yl)-3a,4,5,9b-3H-cyclopenta(c)quinoline ; Benzodioxoles ; GPER1 protein, human ; GPER1 protein, mouse ; Interferon Type I ; Quinolines ; Receptors, Estrogen ; Receptors, G-Protein-Coupled
Language	English
Publishing date	2021-01-15
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	128410-1
ISSN	1095-9203 ; 0036-8075
ISSN (online)	1095-9203
ISSN	0036-8075
DOI	10.1126/science.aba9001
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Zs.A 27: 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 77: Show issues

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Article: Chemokine receptors as important regulators of pathogenesis during arboviral encephalitis.

Michlmayr, Daniela / Lim, Jean K

Frontiers in cellular neuroscience

2014 Volume 8, Page(s) 264

Abstract: The central nervous system (CNS) is a highly complex network comprising long-lived neurons and glial cells. Accordingly, numerous mechanisms have evolved to tightly regulate the initiation of inflammatory responses within the brain. Under ... ...

Abstract	The central nervous system (CNS) is a highly complex network comprising long-lived neurons and glial cells. Accordingly, numerous mechanisms have evolved to tightly regulate the initiation of inflammatory responses within the brain. Under neuroinflammatory conditions, as in the case of viral encephalitides, the infiltration of leukocytes is often required for efficient viral clearance and recovery. The orchestration of leukocyte migration into the inflamed CNS is largely coordinated by a large family of chemotactic cytokines and their receptors. In this review, we will summarize our current understanding of how chemokines promote protection or pathogenesis during arbovirus induced encephalitis, focusing on neurotropic flaviviruses and alphaviruses. Furthermore, we will highlight the latest developments in chemokine and chemokine receptor based drugs that could have potential as therapeutics and have been shown to play a pivotal role in shaping the outcome of disease.
Language	English
Publishing date	2014-09-30
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2452963-1
ISSN	1662-5102
ISSN	1662-5102
DOI	10.3389/fncel.2014.00264
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Article ; Online: Evaluating the Safety of West Nile Virus Immunity During Congenital Zika Virus Infection in Mice.

Acklin, Joshua A / Cattle, Javier D / Moss, Arianna S / Brown, Julia A / Foster, Gregory A / Krysztof, David / Stramer, Susan L / Lim, Jean K

Frontiers in immunology

2021 Volume 12, Page(s) 686411

Abstract: Antibody-dependent enhancement (ADE) is a phenomenon that occurs when cross-reactive antibodies generated from a previous flaviviral infection increase the pathogenesis of a related virus. Zika virus (ZIKV) is the most recent flavivirus introduced to the ...

Abstract	Antibody-dependent enhancement (ADE) is a phenomenon that occurs when cross-reactive antibodies generated from a previous flaviviral infection increase the pathogenesis of a related virus. Zika virus (ZIKV) is the most recent flavivirus introduced to the Western Hemisphere and has become a significant public health threat due to the unanticipated impact on the developing fetus. West Nile virus (WNV) is the primary flavivirus that circulates in North America, and we and others have shown that antibodies against WNV are cross-reactive to ZIKV. Thus, there is concern that WNV immunity could increase the risk of severe ZIKV infection, particularly during pregnancy. In this study, we examined the extent to which WNV antibodies could impact ZIKV pathogenesis in a murine pregnancy model. To test this, we passively transferred WNV antibodies into pregnant
MeSH term(s)	Animals ; Antibodies, Neutralizing/immunology ; Antibodies, Viral/immunology ; Antibody-Dependent Enhancement/immunology ; Cross Reactions/immunology ; Female ; Male ; Mice ; Mice, Knockout ; Neutralization Tests ; Pregnancy ; STAT2 Transcription Factor/genetics ; Viral Load ; West Nile Fever/immunology ; West Nile virus/immunology ; Zika Virus/immunology ; Zika Virus Infection/immunology ; Zika Virus Infection/prevention & control
Chemical Substances	Antibodies, Neutralizing ; Antibodies, Viral ; STAT2 Transcription Factor ; Stat2 protein, mouse
Language	English
Publishing date	2021-06-18
Publishing country	Switzerland
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2021.686411
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Article ; Online: The role of chemokines in the pathogenesis of neurotropic flaviviruses.

Bardina, Susana V / Lim, Jean K

Immunologic research

2012 Volume 54, Issue 1-3, Page(s) 121–132

Abstract: Neurotropic flaviviruses are important emerging and reemerging arthropod-borne pathogens that cause significant morbidity and mortality in humans and other vertebrates worldwide. Upon entry and infection of the CNS, these viruses can induce a rapid ... ...

Abstract	Neurotropic flaviviruses are important emerging and reemerging arthropod-borne pathogens that cause significant morbidity and mortality in humans and other vertebrates worldwide. Upon entry and infection of the CNS, these viruses can induce a rapid inflammatory response characterized by the infiltration of leukocytes into the brain parenchyma. Chemokines and their receptors are involved in coordinating complex leukocyte trafficking patterns that regulate viral pathogenesis in vivo. In this review, we will summarize the current literature on the role of chemokines in regulating the pathogenesis of West Nile, Japanese encephalitis, and tick-borne encephalitis virus infections in mouse models and humans. Understanding how viral infections trigger chemokines, the key cellular events that occur during the infection process, as well as the immunopathogenic role of these cells, are critical areas of research that may ultimately guide a much needed effort toward developing specific immunomodulators and/or antiviral therapeutics.
MeSH term(s)	Animals ; Chemokines/immunology ; Encephalitis, Arbovirus/immunology ; Encephalitis, Arbovirus/virology ; Flavivirus/pathogenicity ; Flavivirus Infections/immunology ; Flavivirus Infections/virology ; Humans ; Receptors, Chemokine/immunology
Chemical Substances	Chemokines ; Receptors, Chemokine
Language	English
Publishing date	2012-05-02
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Review
ZDB-ID	632857-x
ISSN	1559-0755 ; 0257-277X
ISSN (online)	1559-0755
ISSN	0257-277X
DOI	10.1007/s12026-012-8333-3
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Article ; Online: Passenger Mutations Confound Phenotypes of SARM1-Deficient Mice.

Uccellini, Melissa B / Bardina, Susana V / Sánchez-Aparicio, Maria Teresa / White, Kris M / Hou, Ying-Ju / Lim, Jean K / García-Sastre, Adolfo

Cell reports

2020 Volume 31, Issue 1, Page(s) 107498

Abstract: The Toll/IL-1R-domain-containing adaptor protein SARM1 is expressed primarily in the brain, where it mediates axonal degeneration. Roles for SARM1 in TLR signaling, viral infection, inflammasome activation, and chemokine and Xaf1 expression have also ... ...

Abstract	The Toll/IL-1R-domain-containing adaptor protein SARM1 is expressed primarily in the brain, where it mediates axonal degeneration. Roles for SARM1 in TLR signaling, viral infection, inflammasome activation, and chemokine and Xaf1 expression have also been described. Much of the evidence for SARM1 function relies on SARM1-deficient mice generated in 129 ESCs and backcrossed to B6. The Sarm1 gene lies in a gene-rich region encompassing Xaf1 and chemokine loci, which remain 129 in sequence. We therefore generated additional knockout strains on the B6 background, confirming the role of SARM1 in axonal degeneration and WNV infection, but not in VSV or LACV infection, or in chemokine or Xaf1 expression. Sequence variation in proapoptotic Xaf1 between B6 and 129 results in coding changes and distinct splice variants, which may account for phenotypes previously attributed to SARM1. Reevaluation of phenotypes in these strains will be critical for understanding the function of SARM1.
MeSH term(s)	Adaptor Proteins, Signal Transducing/metabolism ; Animals ; Apoptosis/genetics ; Apoptosis Regulatory Proteins/metabolism ; Armadillo Domain Proteins/genetics ; Armadillo Domain Proteins/metabolism ; Axons/metabolism ; Brain/metabolism ; Cytoskeletal Proteins/genetics ; Cytoskeletal Proteins/metabolism ; Encephalitis, California/genetics ; Eye Diseases, Hereditary ; Female ; La Crosse virus ; Male ; Mice ; Mice, 129 Strain ; Mice, Inbred C57BL ; Mice, Knockout ; Mutation/genetics ; Phenotype ; Receptors, Interleukin-1/metabolism ; Retinal Degeneration ; Signal Transduction/genetics ; Toll-Like Receptors/metabolism ; Tumor Necrosis Factor-alpha/metabolism ; Vision Disorders ; West Nile Fever/genetics
Chemical Substances	Adaptor Proteins, Signal Transducing ; Apoptosis Regulatory Proteins ; Armadillo Domain Proteins ; Cytoskeletal Proteins ; Receptors, Interleukin-1 ; SARM1 protein, mouse ; Toll-Like Receptors ; Tumor Necrosis Factor-alpha ; XAF1 protein, mouse
Language	English
Publishing date	2020-04-08
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2649101-1
ISSN	2211-1247 ; 2211-1247
ISSN (online)	2211-1247
ISSN	2211-1247
DOI	10.1016/j.celrep.2020.03.062
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Article ; Online: Chemokine control of West Nile virus infection.

Lim, Jean K / Murphy, Philip M

Experimental cell research

2011 Volume 317, Issue 5, Page(s) 569–574

Abstract: West Nile virus (WNV) is a re-emerging pathogen responsible for fatal outbreaks of meningoencephalitis in humans. Recent research using a mouse model of infection has indicated that specific chemokines and chemokine receptors help mediate the host ... ...

Abstract	West Nile virus (WNV) is a re-emerging pathogen responsible for fatal outbreaks of meningoencephalitis in humans. Recent research using a mouse model of infection has indicated that specific chemokines and chemokine receptors help mediate the host response to WNV acting by at least three mechanisms: control of early neutrophil recruitment to the infection site (Cxcr2), control of monocytosis in blood (Ccr2) and control of leukocyte movement from blood to brain (Cxcr4, Cxcr3, Cxcl10 and possibly Ccr5). CCR5 also appears to be important in human infection, since individuals genetically deficient in this receptor have increased risk of symptomatic disease once infected. These findings provide detailed insight into non-redundant chemokine roles in organ-specific leukocyte recruitment during infection, and emphasize the importance of the balance between pathogen control and immunopathology in determining overall clinical outcome.
MeSH term(s)	Animals ; Chemokines/immunology ; Humans ; Leukocytes/immunology ; Leukocytes/virology ; Neutrophils/immunology ; Neutrophils/virology ; Receptors, Chemokine/immunology ; West Nile virus/immunology ; West Nile virus/isolation & purification
Chemical Substances	Chemokines ; Receptors, Chemokine
Language	English
Publishing date	2011-03-04
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Intramural ; Review
ZDB-ID	1493-x
ISSN	1090-2422 ; 0014-4827
ISSN (online)	1090-2422
ISSN	0014-4827
DOI	10.1016/j.yexcr.2011.01.009
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Article ; Online: Zika virus tropism during early infection of the testicular interstitium and its role in viral pathogenesis in the testes.

Tsetsarkin, Konstantin A / Acklin, Joshua A / Liu, Guangping / Kenney, Heather / Teterina, Natalia L / Pletnev, Alexander G / Lim, Jean K

PLoS pathogens

2020 Volume 16, Issue 7, Page(s) e1008601

Abstract: Sexual transmission and persistence of Zika virus (ZIKV) in the testes pose new challenges for controlling virus outbreaks and developing live-attenuated vaccines. It has been shown that testicular infection of ZIKV is initiated in the testicular ... ...

Abstract	Sexual transmission and persistence of Zika virus (ZIKV) in the testes pose new challenges for controlling virus outbreaks and developing live-attenuated vaccines. It has been shown that testicular infection of ZIKV is initiated in the testicular interstitium, followed by spread of the virus in the seminiferous tubules. This leads to testicular damage and/or viral dissemination into the epididymis and eventually into semen. However, it remains unknown which cell types are targeted by ZIKV in the testicular interstitium, and what is the specific order of infectious events leading to ZIKV invasion of the seminiferous tubules. Here, we demonstrate that interstitial leukocytes expressing mir-511-3p microRNA are the initial targets of ZIKV in the testes, and infection of mir-511-3p-expressing cells in the testicular interstitium is necessary for downstream infection of the seminiferous tubules. Mir-511-3p is expressed concurrently with CD206, a marker of lineage 2 (M2) macrophages and monocyte derived dendritic cells (moDCs). Selective restriction of ZIKV infection of CD206-expressing M2 macrophages/moDCs results in the attenuation of macrophage-associated inflammatory responses in vivo and prevents the disruption of the Sertoli cell barrier in vitro. Finally, we show that targeting of viral genome for mir-511-3p significantly attenuates early ZIKV replication not only in the testes, but also in many peripheral organs, including spleen, epididymis, and pancreas. This incriminates M2 macrophages/moDCs as important targets for visceral ZIKV replication following hematogenous dissemination of the virus from the site of infection.
MeSH term(s)	Animals ; Dendritic Cells/virology ; Macrophages/virology ; Male ; Mice ; Testis/virology ; Viral Tropism/physiology ; Zika Virus/physiology ; Zika Virus Infection/virology
Language	English
Publishing date	2020-07-02
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, N.I.H., Intramural
ZDB-ID	2205412-1
ISSN	1553-7374 ; 1553-7374
ISSN (online)	1553-7374
ISSN	1553-7374
DOI	10.1371/journal.ppat.1008601
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Article: Sex differences in cytokine production following West Nile virus infection: Implications for symptom manifestation

Hoffman, Kevin W / Lee, Jakleen J / Foster, Gregory A / Krysztof, David / Stramer, Susan L / Lim, Jean K

Pathogens and disease. 2019 Mar. 27, v. 77, no. 2

2019

Abstract: West Nile virus (WNV) infection outcomes vary among individuals, with most infections resulting in asymptomatic or mild flu-like symptoms. We previously reported an association between early cytokine production and symptom outcome following WNV infection ...

Abstract	West Nile virus (WNV) infection outcomes vary among individuals, with most infections resulting in asymptomatic or mild flu-like symptoms. We previously reported an association between early cytokine production and symptom outcome following WNV infection in US blood donors. In this meta-analysis, we found that WNV-infected females reported more symptoms than WNV-infected males, despite similar initial viremia and type I interferon responses. As the infection progressed, males exhibited a protracted cytokine response—marked by sustained CCL2 (MCP-1), CCL11 (eotaxin-1), CXCL10 (IP-10) and IL-15—that was absent in females. Our results suggest that sex differences may be a factor in sustaining WNV immunity.
Keywords	West Nile virus ; blood donors ; chemokine CCL11 ; chemokine CCL2 ; chemokine CXCL10 ; females ; gender differences ; immunity ; interferons ; males ; meta-analysis ; viremia ; United States
Language	English
Dates of publication	2019-0327
Publishing place	Oxford University Press
Document type	Article
ISSN	2049-632X
DOI	10.1093/femspd/ftz016
Database	NAL-Catalogue (AGRICOLA)

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