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Article ; Online: The CD133 and CD34 cell types in human umbilical cord blood have the capacity to produce infectious dengue virus particles.

Vats, Amrita / Ho, Tzu-Chuan / Puc, Irwin / Chang, Chiung-Hsin / Perng, Guey-Chuen / Chen, Po-Lin

2023 Volume 13, Issue 1, Page(s) 10513

Abstract: Although dengue virus (DENV) can establish infections in hematopoietic stem progenitor cells (HSPCs), there is little information on dengue virus persistent infection in CD34+ and CD133+ cell surface glycoproteins of hematopoietic stem cells (HSCs). CD34 ...

Abstract	Although dengue virus (DENV) can establish infections in hematopoietic stem progenitor cells (HSPCs), there is little information on dengue virus persistent infection in CD34+ and CD133+ cell surface glycoproteins of hematopoietic stem cells (HSCs). CD34 and CD133 also function as cell-cell adhesion factors, which are present in umbilical cord blood (UCB). In this study, we sought to establish a persistent infection model of DENV infection in UCB using a prolonged period of infection lasting 30 days. Post-infection, the results exhibited a productive and non-productive phase of DENV production. Using a plaque assay, Western blot, and confocal microscopy, we demonstrated that CD133 and CD34 cells are target cells for DENV infection. Moreover, we showed that DENV particles can be recovered from the non-productive phase of DENV-infected CD34 and CD133 cells after co-incubation with Vero cells. We concluded that CD133 and CD34 retain their capacity to produce the infectious virus due to proliferation and their ability to repopulate, as deduced from a BrdU proliferation assay and flow cytometry analysis using t-distributed stochastic neighbor embedding. In summary, the platform to co-culture infected primitive HSCs from their non-productive phase onto Vero cells will give new insights into understanding the DENV dynamics in cell-to-cell transmission and reactivation of the virus.
MeSH term(s)	Chlorocebus aethiops ; Animals ; Humans ; Fetal Blood ; Persistent Infection ; Vero Cells ; Antigens, CD34 ; Virion ; Dengue
Chemical Substances	Antigens, CD34
Language	English
Publishing date	2023-06-29
Publishing country	England
Document type	Journal Article
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-023-37707-8
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Role of Bone Marrow in Pathogenesis of Viral Infections.

Perng, Guey Chuen

Journal of bone marrow research

2014 Volume 1

Language	English
Publishing date	2014-08-22
Publishing country	United States
Document type	Journal Article
DOI	10.4172/2329-8820.1000104
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Novel concept on antiviral strategies to dengue.

Lo, Yu-Chih / Perng, Guey Chuen

Current opinion in virology

2016 Volume 18, Page(s) 97–108

Abstract: Recent evidence has revealed that asymptomatic and/or persistent dengue virus (DENV) infections play a role in the cycling pattern of dengue outbreaks. These findings add a new dimension to the continually evolving search for effective prevention ... ...

Abstract	Recent evidence has revealed that asymptomatic and/or persistent dengue virus (DENV) infections play a role in the cycling pattern of dengue outbreaks. These findings add a new dimension to the continually evolving search for effective prevention strategies in dengue. Disappointing outcomes of clinical trials in anti-dengue modalities have become commonplace. These failures may result from confounding variables and/or unresolved scientific issues that surround dengue, including the replication cycle of DENV in a natural setting, the target cells and reservoir for viral replication in vivo, and the effect of asymptomatic/persistent carriers in the dissemination of dengue. This article sets forth to address these issues using the most updated information available in the literature and to propose a novel antiviral strategy for the prevention and control of dengue.
MeSH term(s)	Aedes/virology ; Animals ; Antiviral Agents/therapeutic use ; Asymptomatic Infections ; Carrier State/virology ; Dengue/drug therapy ; Dengue/prevention & control ; Dengue/virology ; Dengue Virus/drug effects ; Dengue Virus/pathogenicity ; Dengue Virus/physiology ; Dengue Virus/ultrastructure ; Humans ; Viremia ; Virion/chemistry ; Virion/drug effects ; Virus Replication
Chemical Substances	Antiviral Agents
Language	English
Publishing date	2016-06
Publishing country	Netherlands
Document type	Journal Article ; Review
ZDB-ID	2611378-8
ISSN	1879-6265 ; 1879-6257
ISSN (online)	1879-6265
ISSN	1879-6257
DOI	10.1016/j.coviro.2016.05.009
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Article: Antrodia cinnamomea

Chen, Yi-Ju / Tsao, Yu-Cian / Ho, Tzu-Chuan / Puc, Irwin / Chen, Chia-Chang / Perng, Guey-Chuen / Lien, Hsiu-Man

Plants (Basel, Switzerland)

2022 Volume 11, Issue 19

Abstract: Dengue caused by dengue virus (DENV) is a mosquito-borne disease. Dengue exhibits a wide range of symptoms, ranging from asymptomatic to flu-like illness, and a few symptomatic cases may develop into severe dengue, leading to death. However, there are no ...

Abstract	Dengue caused by dengue virus (DENV) is a mosquito-borne disease. Dengue exhibits a wide range of symptoms, ranging from asymptomatic to flu-like illness, and a few symptomatic cases may develop into severe dengue, leading to death. However, there are no effective and safe therapeutics for DENV infections. We have previously reported that cytokine expression, especially inflammatory cytokines, was altered in patients with different severities of dengue.
Language	English
Publishing date	2022-10-06
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2704341-1
ISSN	2223-7747
ISSN	2223-7747
DOI	10.3390/plants11192631
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Article ; Online: Suppression of annexin A1 and its receptor reduces herpes simplex virus 1 lethality in mice.

Wang, Li-Chiu / Wu, Shang-Rung / Yao, Hui-Wen / Ling, Pin / Perng, Guey-Chuen / Chiu, Yen-Chi / Hsu, Sheng-Min / Chen, Shun-Hua

PLoS pathogens

2022 Volume 18, Issue 8, Page(s) e1010692

Abstract: Herpes simplex virus 1 (HSV-1)-induced encephalitis is the most common cause of sporadic, fatal encephalitis in humans. HSV-1 has at least 10 different envelope glycoproteins, which can promote virus infection. The ligands for most of the envelope ... ...

Abstract	Herpes simplex virus 1 (HSV-1)-induced encephalitis is the most common cause of sporadic, fatal encephalitis in humans. HSV-1 has at least 10 different envelope glycoproteins, which can promote virus infection. The ligands for most of the envelope glycoproteins and the significance of these ligands in virus-induced encephalitis remain elusive. Here, we show that glycoprotein E (gE) binds to the cellular protein, annexin A1 (Anx-A1) to enhance infection. Anx-A1 can be detected on the surface of cells permissive for HSV-1 before infection and on virions. Suppression of Anx-A1 or its receptor, formyl peptide receptor 2 (FPR2), on the cell surface and gE or Anx-A1 on HSV-1 envelopes reduced virus binding to cells. Importantly, Anx-A1 knockout, Anx-A1 knockdown, or treatments with the FPR2 antagonist reduced the mortality and tissue viral loads of infected mice. Our results show that Anx-A1 is a novel enhancing factor of HSV-1 infection. Anx-A1-deficient mice displayed no evident physiology and behavior changes. Hence, targeting Anx-A1 and FPR2 could be a promising prophylaxis or adjuvant therapy to decrease HSV-1 lethality.
MeSH term(s)	Animals ; Annexin A1/genetics ; Annexin A1/metabolism ; Encephalitis ; Glycoproteins/metabolism ; Herpes Simplex ; Herpesvirus 1, Human/metabolism ; Humans ; Mice
Chemical Substances	Annexin A1 ; Glycoproteins
Language	English
Publishing date	2022-08-08
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2205412-1
ISSN	1553-7374 ; 1553-7374
ISSN (online)	1553-7374
ISSN	1553-7374
DOI	10.1371/journal.ppat.1010692
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Short-term, medium-term, and long-term risks of nonvariceal upper gastrointestinal bleeding after dengue virus infection.

Chien, Yu-Wen / Chuang, Hui-Ning / Wang, Yu-Ping / Perng, Guey Chuen / Chi, Chia-Yu / Shih, Hsin-I

PLoS neglected tropical diseases

2022 Volume 16, Issue 1, Page(s) e0010039

Abstract: Dengue patients have an increased risk of acute gastrointestinal (GI) bleeding. However, whether dengue virus (DENV) infection can cause an increased long-term risk of GI bleeding remains unknown, especially among elderly individuals who commonly take ... ...

Abstract	Dengue patients have an increased risk of acute gastrointestinal (GI) bleeding. However, whether dengue virus (DENV) infection can cause an increased long-term risk of GI bleeding remains unknown, especially among elderly individuals who commonly take antithrombotic drugs. A retrospective population-based cohort study was conducted by analyzing the National Health Insurance Research Databases. Laboratory-confirmed dengue patients from 2002 to 2012 and four matched nondengue controls were identified. Multivariate Cox proportional hazard regression was used to evaluate the acute (<30 days), medium-term (31-365 days), and long-term (>365 days) risks of nonvariceal upper GI bleeding after DENV infection. Stratified analyses by age group (≤50, 51-64, ≥65 years old) were also performed. In total, 13267 confirmed dengue patients and 53068 nondengue matched controls were included. After adjusting for sex, age, area of residence, comorbidities, and medications, dengue patients had a significantly increased risk of nonvariceal upper GI bleeding within 30 days of disease onset (adjusted HR 55.40; 95% CI: 32.17-95.42). However, DENV infection was not associated with increased medium-term and long-term risks of upper GI bleeding overall or in each age group. Even dengue patients who developed acute GI bleeding did not have increased medium-term (adjusted HR; 0.55, 95% CI 0.05-6.18) and long-term risks of upper GI bleeding (adjusted HR; 1.78, 95% CI 0.89-3.55). DENV infection was associated with a significantly increased risk of nonvariceal upper GI bleeding within 30 days but not thereafter. Recovered dengue patients with acute GI bleeding can resume antithrombotic treatments to minimize the risk of thrombosis.
MeSH term(s)	Adolescent ; Adult ; Aged ; Child ; Child, Preschool ; Cohort Studies ; Dengue/complications ; Female ; Gastrointestinal Hemorrhage/etiology ; Humans ; Infant ; Male ; Middle Aged ; Retrospective Studies ; Young Adult
Language	English
Publishing date	2022-01-19
Publishing country	United States
Document type	Journal Article
ZDB-ID	2429704-5
ISSN	1935-2735 ; 1935-2735
ISSN (online)	1935-2735
ISSN	1935-2735
DOI	10.1371/journal.pntd.0010039
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Current neurological observations and complications of dengue virus infection.

Solbrig, Marylou V / Perng, Guey-Chuen

Current neurology and neuroscience reports

2015 Volume 15, Issue 6, Page(s) 29

Abstract: Dengue, a mosquito-borne flavivirus and fastest growing tropical disease in the world, has experienced an explosion of neurologic case reports and series in recent years. Now dengue is a frequent or leading cause of encephalitis in some endemic regions, ... ...

Abstract	Dengue, a mosquito-borne flavivirus and fastest growing tropical disease in the world, has experienced an explosion of neurologic case reports and series in recent years. Now dengue is a frequent or leading cause of encephalitis in some endemic regions, is estimated to infect one in six tourists returning from the tropics, and has been proven to have local transmission within the continental USA. High documentation of neurologic disease in recent years reflects increases in overall cases, enhanced clinical awareness and advances in diagnostics. Neurological aspects of dengue virus, along with epidemiology, treatment, and vaccine progress, are presented.
MeSH term(s)	Dengue/complications ; Dengue Virus ; Humans ; Immunity, Heterologous ; Nervous System Diseases/etiology ; Nervous System Diseases/prevention & control ; Nervous System Diseases/therapy ; Treatment Outcome
Language	English
Publishing date	2015-06
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2057363-7
ISSN	1534-6293 ; 1528-4042
ISSN (online)	1534-6293
ISSN	1528-4042
DOI	10.1007/s11910-015-0550-4
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Use of Animal Models in Studying Roles of Antibodies and Their Secretion Cells in Dengue Vaccine Development

Chokephaibulkit, Kulkanya / Chien, Yu-Wen / AbuBakar, Sazaly / Pattanapanyasat, Kovit / Perng, Guey Chuen

Viruses. 2020 Nov. 05, v. 12, no. 11

2020

Abstract: The cardinal feature of adaptive immunity is its ability to form memory responses that can be rapidly recalled to contain pathogens upon reencountering. Conferring a robust memory immune response to an infection is a key feature for a successful ... ...

Abstract	The cardinal feature of adaptive immunity is its ability to form memory responses that can be rapidly recalled to contain pathogens upon reencountering. Conferring a robust memory immune response to an infection is a key feature for a successful vaccination program. The plasmablasts are cells that not only can secret non-neutralizing antibodies but also can secrete the specific antibodies essential to neutralize and inactivate the invading pathogens. Dengue has been recognized as one of the most important vector-borne human viral diseases globally. Currently, supportive care with vigilant monitoring is the standard practice since there is as yet no approved therapeutic modality to treat dengue. Even though the approved vaccine has become available, its low efficacy with the potential to cause harm is the major hurdle to promote the widespread usage of the vaccine. Despite the decades of research on dengue, the major challenge in dengue vaccine development is the absence of suitable experimental animal models that reflect the pathological features and clinical symptoms, as seen in humans. Dengue is transmitted by the bite of mosquitoes carrying infectious dengue virus (DENV), which has four distinct serotypes. Recently, cases resulting from unconventional transmission routes, such as blood transfusion, organs as well as stem cells and bone marrow transplantations, and mother-to-infant vertical transmission, have been reported, suggesting an alternate route of DENV transmission exists in nature. This review discusses issues and challenges needing to be resolved to develop an effective dengue vaccine. Development of a robust and reliable dengue animal model that can reflect not only dynamic human clinical symptoms but also can answer around why preexisting neutralizing antibodies do not confer protection upon re-infection and immune protection marker for dengue vaccine efficacy evaluation.
Keywords	Culicidae ; Dengue virus ; animal models ; blood transfusion ; bone marrow ; dengue ; humans ; immune response ; immunologic memory ; laboratory animals ; monitoring ; neutralization ; neutralizing antibodies ; pathogens ; secretion ; serotypes ; signs and symptoms (animals and humans) ; stem cells ; vaccination ; vaccine development ; vaccines
Language	English
Dates of publication	2020-1105
Publishing place	Multidisciplinary Digital Publishing Institute
Document type	Article
ZDB-ID	2516098-9
ISSN	1999-4915
ISSN	1999-4915
DOI	10.3390/v12111261
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Use of Animal Models in Studying Roles of Antibodies and Their Secretion Cells in Dengue Vaccine Development.

Chokephaibulkit, Kulkanya / Chien, Yu-Wen / AbuBakar, Sazaly / Pattanapanyasat, Kovit / Perng, Guey Chuen

Viruses

2020 Volume 12, Issue 11

Abstract	The cardinal feature of adaptive immunity is its ability to form memory responses that can be rapidly recalled to contain pathogens upon reencountering. Conferring a robust memory immune response to an infection is a key feature for a successful vaccination program. The plasmablasts are cells that not only can secret non-neutralizing antibodies but also can secrete the specific antibodies essential to neutralize and inactivate the invading pathogens. Dengue has been recognized as one of the most important vector-borne human viral diseases globally. Currently, supportive care with vigilant monitoring is the standard practice since there is as yet no approved therapeutic modality to treat dengue. Even though the approved vaccine has become available, its low efficacy with the potential to cause harm is the major hurdle to promote the widespread usage of the vaccine. Despite the decades of research on dengue, the major challenge in dengue vaccine development is the absence of suitable experimental animal models that reflect the pathological features and clinical symptoms, as seen in humans. Dengue is transmitted by the bite of mosquitoes carrying infectious dengue virus (DENV), which has four distinct serotypes. Recently, cases resulting from unconventional transmission routes, such as blood transfusion, organs as well as stem cells and bone marrow transplantations, and mother-to-infant vertical transmission, have been reported, suggesting an alternate route of DENV transmission exists in nature. This review discusses issues and challenges needing to be resolved to develop an effective dengue vaccine. Development of a robust and reliable dengue animal model that can reflect not only dynamic human clinical symptoms but also can answer around why preexisting neutralizing antibodies do not confer protection upon re-infection and immune protection marker for dengue vaccine efficacy evaluation.
MeSH term(s)	Adaptive Immunity ; Animals ; Antibodies, Neutralizing/immunology ; Antibodies, Viral/immunology ; Dengue/immunology ; Dengue/prevention & control ; Dengue Vaccines/immunology ; Dengue Virus/immunology ; Disease Models, Animal ; Global Health ; Humans ; Mosquito Vectors/virology ; Plasma Cells/immunology ; Vaccination
Chemical Substances	Antibodies, Neutralizing ; Antibodies, Viral ; Dengue Vaccines
Language	English
Publishing date	2020-11-05
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2516098-9
ISSN	1999-4915 ; 1999-4915
ISSN (online)	1999-4915
ISSN	1999-4915
DOI	10.3390/v12111261
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Risk of Leukemia after Dengue Virus Infection: A Population-Based Cohort Study.

Chien, Yu-Wen / Wang, Chia-Chun / Wang, Yu-Ping / Lee, Cho-Yin / Perng, Guey Chuen

Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology

2020 Volume 29, Issue 3, Page(s) 558–564

Abstract: Background: Infections account for about 15% of human cancers globally. Although abnormal hematologic profiles and bone marrow suppression are common in patients with dengue, whether dengue is associated with a higher risk of leukemia has not been ... ...

Abstract	Background: Infections account for about 15% of human cancers globally. Although abnormal hematologic profiles and bone marrow suppression are common in patients with dengue, whether dengue is associated with a higher risk of leukemia has not been investigated. Methods: We conducted a nationwide population-based cohort study by analyzing the National Health Insurance Research Databases in Taiwan. Laboratory-confirmed dengue patients between 2002 and 2011 were identified; five matched non-dengue controls were randomly selected for each patient. Follow-up ended on December 31, 2015. Multivariate Cox proportional hazard regression models were used to evaluate the effect of dengue virus infection on the risk of leukemia. Cancers other than leukemia were used as falsification endpoints to evaluate the validity of this study. Results: We identified 12,573 patients with dengue and 62,865 non-dengue controls. Patients with dengue had a higher risk of leukemia [adjusted HR, 2.03; 95% confidence interval (CI), 1.16-3.53]. Stratified analyses by different follow-up periods showed that dengue virus infection was significantly associated with a higher risk of leukemia only between 3 and 6 years after infection (adjusted HR, 3.22; 95% CI, 1.25-8.32). There was no significant association between dengue and the risk of other cancers. Conclusions: This study provides the first epidemiologic evidence for the association between dengue virus infection and leukemia. Impact: Considering the rapidly increasing global incidence of dengue and the burden of leukemia, further studies are required to verify this association and to unravel the potential mechanisms of pathogenesis.
MeSH term(s)	Adolescent ; Adult ; Aged ; Causality ; Child ; Child, Preschool ; Dengue/diagnosis ; Dengue/epidemiology ; Dengue/virology ; Dengue Virus/isolation & purification ; Female ; Follow-Up Studies ; Humans ; Incidence ; Infant ; Infant, Newborn ; Leukemia/epidemiology ; Male ; Middle Aged ; Proportional Hazards Models ; Risk Assessment/statistics & numerical data ; Risk Factors ; Taiwan/epidemiology ; Young Adult
Language	English
Publishing date	2020-02-12
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1153420-5
ISSN	1538-7755 ; 1055-9965
ISSN (online)	1538-7755
ISSN	1055-9965
DOI	10.1158/1055-9965.EPI-19-1214
Database	MEDical Literature Analysis and Retrieval System OnLINE

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