scholarly journals TIM-1 As a Signal Receptor Triggers Dengue Virus-Induced Autophagy

2019 ◽  
Vol 20 (19) ◽  
pp. 4893 ◽  
Author(s):  
Li-Wei Chu ◽  
Chia-Jui Yang ◽  
Kuan-Jen Peng ◽  
Pei-Ling Chen ◽  
Shuu-Jiun Wang ◽  
...  
Keyword(s):  
T Cell ◽  
Dengue Virus ◽  
Light Chain ◽  
Denv Infection ◽  
Cellular Internalization ◽  
Apoptotic Body ◽  
Autophagy Induction ◽  
A Subunit ◽  
Confocal Images ◽  
Body Clearance

Dengue virus (DENV) infection triggers the activation of autophagy to facilitate the viral replication cycle from various aspects. Although a number of stimulators are proposed to activate autophagy, none of them appears prior to the uncoating process. Given that T-cell immunoglobulin and mucin domain 1 (TIM-1) receptor is a putative DENV receptor and promotes apoptotic body clearance by autophagy induction, it raises the possibility that TIM-1 may participate in the activation of DENV-induced autophagy. In this study, confocal images first revealed the co-localization of TIM-1 with autophagosomes in DENV-induced autophagy rather than rapamycin-induced autophagy, suggesting the co-transportation of TIM-1 with DENV during infection. The treatment of siRNA to knockdown TIM-1 expression in DENV-infected GFP-microtubule-associated protein light chain 3 (LC3)-Huh7.5 cells revealed that TIM-1 is required not only for DENV cellular internalization but also for autophagy activation. Furthermore, knockdown p85, a subunit of phosphoinositide 3-kinases (PI3Ks), which is co-localized with TIM-1 at rab5-positive endosomes caused the reduction of autophagy, indicating that TIM-1-mediated DENV-induced autophagy requires p85. Taken together, the current study uncovered TIM-1 as a novel factor for triggering autophagy in DENV infection through TIM-1-p85 axis, in addition to serving as a DENV receptor.

scholarly journals Diagnostic differentiation of Zika and dengue virus exposure by analyzing T cell receptor sequences from peripheral blood of infected HLA-A2 transgenic mice

2020 ◽  
Vol 14 (12) ◽  
pp. e0008896
Author(s):  
Mariah Hassert ◽  
Kyle J. Wolf ◽  
Ahmad Rajeh ◽  
Courtney Schiebout ◽  
Stella G. Hoft ◽  
...  
Keyword(s):  
T Cell ◽  
Dengue Virus ◽  
T Cell Receptor ◽  
Zika Virus ◽  
Cell Receptor ◽  
Denv Infection ◽  
Sequencing Platform ◽  
Diagnostic Assays ◽  
Virus Exposure ◽  
Rapid Emergence

Zika virus (ZIKV) is a significant global health threat due to its potential for rapid emergence and association with severe congenital malformations during infection in pregnancy. Despite the urgent need, accurate diagnosis of ZIKV infection is still a major hurdle that must be overcome. Contributing to the inaccuracy of most serologically-based diagnostic assays for ZIKV, is the substantial geographic and antigenic overlap with other flaviviruses, including the four serotypes of dengue virus (DENV). Within this study, we have utilized a novel T cell receptor (TCR) sequencing platform to distinguish between ZIKV and DENV infections. Using high-throughput TCR sequencing of lymphocytes isolated from DENV and ZIKV infected mice, we were able to develop an algorithm which could identify virus-associated TCR sequences uniquely associated with either a prior ZIKV or DENV infection in mice. Using this algorithm, we were then able to separate mice that had been exposed to ZIKV or DENV infection with 97% accuracy. Overall this study serves as a proof-of-principle that T cell receptor sequencing can be used as a diagnostic tool capable of distinguishing between closely related viruses. Our results demonstrate the potential for this innovative platform to be used to accurately diagnose Zika virus infection and potentially the next emerging pathogen(s).

scholarly journals Time elapsed between Zika and dengue virus infections affects antibody and T cell responses

2019 ◽  
Author(s):  
Erick X. Pérez-Guzmán ◽  
Petraleigh Pantoja ◽  
Crisanta Serrano-Collazo ◽  
Mariah A. Hassert ◽  
Alexandra Ortiz-Rosa ◽  
...  
Keyword(s):  
T Cell ◽  
Dengue Virus ◽  
Rhesus Macaques ◽  
T Cell Responses ◽  
Denv Infection ◽  
Virus Infections ◽  
Zikv Infection ◽  
Cell Responses ◽  
Inflammatory Status

AbstractThe role of Zika virus (ZIKV) immunity on subsequent dengue virus (DENV) infections is relevant to anticipate the dynamics of forthcoming DENV epidemics in areas with previous ZIKV exposure. We study the effect of ZIKV infection with various strains on subsequent DENV immune response after 10 and 2 months of ZIKV infection in rhesus macaques. Our results show that a subsequent DENV infection in animals with early- and middle-convalescent periods to ZIKV do not promote an increase in DENV viremia nor pro-inflammatory status. Previous ZIKV exposure increases the magnitude of the antibody and T cell responses against DENV, and different time intervals between infections alter the magnitude and durability of such responses—more after longer ZIKV pre-exposure. Collectively, we find no evidence of a detrimental effect of ZIKV immunity in a subsequent DENV infection. This supports the implementation of ZIKV vaccines that could also boost immunity against future DENV epidemics.

scholarly journals Time elapsed between Zika and dengue virus infections affects antibody and T cell responses

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Erick X. Pérez-Guzmán ◽  
Petraleigh Pantoja ◽  
Crisanta Serrano-Collazo ◽  
Mariah A. Hassert ◽  
Alexandra Ortiz-Rosa ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cell ◽  
Dengue Virus ◽  
T Cell Responses ◽  
Denv Infection ◽  
Zikv Infection ◽  
Cell Responses ◽  
Inflammatory Status ◽  
Short Period ◽  
The Impact

Abstract Zika virus (ZIKV) and dengue virus (DENV) are co-endemic in many parts of the world, but the impact of ZIKV infection on subsequent DENV infection is not well understood. Here we show in rhesus macaques that the time elapsed after ZIKV infection affects the immune response to DENV infection. We show that previous ZIKV exposure increases the magnitude of the antibody and T cell responses against DENV. The time interval between ZIKV and subsequent DENV infection further affects the immune response. A mid-convalescent period of 10 months after ZIKV infection results in higher and more durable antibody and T cell responses to DENV infection than a short period of 2 months. In contrast, previous ZIKV infection does not affect DENV viremia or pro-inflammatory status. Collectively, we find no evidence of a detrimental effect of ZIKV immunity in a subsequent DENV infection. This supports the implementation of ZIKV vaccines that could also boost immunity against future DENV epidemics.

scholarly journals T-cell Responses in Individuals Infected with Zika Virus and in Those Vaccinated Against Dengue Virus

2017 ◽  
Vol 2 (2) ◽  
pp. 274 ◽  
Author(s):  
Dominic Paquin-Proulx ◽  
Fabio E. Leal ◽  
Cassia G. Terrassani Silveira ◽  
Alvino Maestri ◽  
Claudia Brockmeyer ◽  
...  
Keyword(s):  
T Cell ◽  
Dengue Virus ◽  
Zika Virus ◽  
Cell Response ◽  
Cell Epitope ◽  
Denv Infection ◽  
Cross Reactivity ◽  
T Cell Response ◽  
Cd4 T Cell ◽  
T Cell Epitopes

Background: The outbreak of Zika virus (ZIKV) infection in Brazil has raised concerns that infection during pregnancy could cause microcephaly and other severe neurodevelopmental malformations in the fetus. The mechanisms by which ZIKV causes fetal abnormalities are largely unknown. The importance of pre-infection with dengue virus (DENV), or other flaviviruses endemic to Brazil, remains to be investigated. It has been reported that antibodies directed against DENV can increase ZIKV infectivity by antibody dependent enhancement (ADE), suggesting that a history of prior DENV infection might worsen the outcome of ZIKV infection.Methods: We used bioinformatics tools to design 18 peptides from the ZIKV envelope containing predicted HLA-I T-cell epitopes and investigated T-cell cross-reactivity between ZIKV-infected individuals and DENV-vaccinated subjects by IFNg ELISPOT.Results: Three peptides induced IFNg production in both ZIKV-infected subjects and in DENV-vaccinated individuals. Flow cytometry indicated that 1 ZIKV peptide induced a CD4+ T-cell response in DENV-vaccinated subjects.Conclusions: We demonstrated that vaccination against DENV induced a T-cell response against ZIKV and identified one such CD4+ T-cell epitope. The ZIKV-reactive CD4+ T cells induced by DENV vaccination and identified in this study could contribute to the appearance of cross-reactive antibodies mediating ADE.

scholarly journals T-cell Responses in Individuals Infected with Zika Virus and in Those Vaccinated Against Dengue Virus

2017 ◽  
Vol 2 (2) ◽  
pp. 274
Author(s):  
Dominic Paquin-Proulx ◽  
Fabio E. Leal ◽  
Cassia G. Terrassani Silveira ◽  
Alvino Maestri ◽  
Claudia Brockmeyer ◽  
...  
Keyword(s):  
T Cell ◽  
Dengue Virus ◽  
Zika Virus ◽  
Cell Response ◽  
Cell Epitope ◽  
Denv Infection ◽  
Cross Reactivity ◽  
T Cell Response ◽  
Cd4 T Cell ◽  
T Cell Epitopes

Background: The outbreak of Zika virus (ZIKV) infection in Brazil has raised concerns that infection during pregnancy could cause microcephaly and other severe neurodevelopmental malformations in the fetus. The mechanisms by which ZIKV causes fetal abnormalities are largely unknown. The importance of pre-infection with dengue virus (DENV), or other flaviviruses endemic to Brazil, remains to be investigated. It has been reported that antibodies directed against DENV can increase ZIKV infectivity by antibody dependent enhancement (ADE), suggesting that a history of prior DENV infection might worsen the outcome of ZIKV infection.Methods: We used bioinformatics tools to design 18 peptides from the ZIKV envelope containing predicted HLA-I T-cell epitopes and investigated T-cell cross-reactivity between ZIKV-infected individuals and DENV-vaccinated subjects by IFNg ELISPOT.Results: Three peptides induced IFNg production in both ZIKV-infected subjects and in DENV-vaccinated individuals. Flow cytometry indicated that 1 ZIKV peptide induced a CD4+ T-cell response in DENV-vaccinated subjects.Conclusions: We demonstrated that vaccination against DENV induced a T-cell response against ZIKV and identified one such CD4+ T-cell epitope. The ZIKV-reactive CD4+ T cells induced by DENV vaccination and identified in this study could contribute to the appearance of cross-reactive antibodies mediating ADE.

An experimental and theoretical approach to understand Fever, DENF & its cure

2020 ◽  
Vol 20 ◽  
Author(s):  
Vijay Kumar Vishvakarma ◽  
Ramesh Chandra ◽  
Prashant Singh
Keyword(s):  
Catalytic Activity ◽  
Dengue Virus ◽  
Theoretical Approach ◽  
Major Part ◽  
Genomic Structure ◽  
Denv Infection ◽  
Structural Proteins ◽  
Experimental Approaches ◽  
Ns3 Protease ◽  
Prime Target

: Fever is a response of human body due to an increase the temperature against the certain stimuli. It may be associated with several reasons and one of the major causes of fever is mosquito bite. Fever due to dengue virus (DENV) infection is being paid most attention out of several other fevers because of a large number of deaths reported worldwide. Dengue virus is transmitted by biting of the mosquitoes, Aedes aegypti and Aedes albopictus. DENV1, DENV2, DENV3 and DENV4 are the four serotypes of dengue virus and these serotypes have 65% similarities in their genomic structure. Genome of DENV is composed of single stranded RNA and it encodes for the polyprotein. Structural and non-structural proteins (nsP) are the two major part of protese. Researchers have paid high attention on the non-structural protease (nsP) of DENV like nsP1, nsP2A, nsP2B, nsP3, nsP4A, nsP4B and nsP5. The NS2B-NS3 protease of DENV is the prime target of the researchers as it is responsible for the catalytic activity. In the present time, Dengvaxia (vaccine) is being recommended to the patients suffering severely due to DENV infection in few countries only. Till date, neither a vaccine nor an effective medicine is available to combat with all four serotypes. This review describes the fever, its causes and studies to cure the infection due to DENV using theoretical and experimental approaches.

scholarly journals Potential Phosphorylation of Viral Nonstructural Protein 1 in Dengue Virus Infection

Viruses ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1393
Author(s):  
Thanyaporn Dechtawewat ◽  
Sittiruk Roytrakul ◽  
Yodying Yingchutrakul ◽  
Sawanya Charoenlappanit ◽  
Bunpote Siridechadilok ◽  
...  
Keyword(s):  
Dengue Virus ◽  
Nonstructural Protein ◽  
Antiviral Drug ◽  
Denv Infection ◽  
Site Directed Mutagenesis ◽  
Phosphorylation Sites ◽  
Post Translational Modification ◽  
Multifunctional Protein ◽  
Nonstructural Protein 1 ◽  
Underlying Mechanisms

Dengue virus (DENV) infection causes a spectrum of dengue diseases that have unclear underlying mechanisms. Nonstructural protein 1 (NS1) is a multifunctional protein of DENV that is involved in DENV infection and dengue pathogenesis. This study investigated the potential post-translational modification of DENV NS1 by phosphorylation following DENV infection. Using liquid chromatography-tandem mass spectrometry (LC-MS/MS), 24 potential phosphorylation sites were identified in both cell-associated and extracellular NS1 proteins from three different cell lines infected with DENV. Cell-free kinase assays also demonstrated kinase activity in purified preparations of DENV NS1 proteins. Further studies were conducted to determine the roles of specific phosphorylation sites on NS1 proteins by site-directed mutagenesis with alanine substitution. The T27A and Y32A mutations had a deleterious effect on DENV infectivity. The T29A, T230A, and S233A mutations significantly decreased the production of infectious DENV but did not affect relative levels of intracellular DENV NS1 expression or NS1 secretion. Only the T230A mutation led to a significant reduction of detectable DENV NS1 dimers in virus-infected cells; however, none of the mutations interfered with DENV NS1 oligomeric formation. These findings highlight the importance of DENV NS1 phosphorylation that may pave the way for future target-specific antiviral drug design.

scholarly journals Phage display demonstrates durable differences in serological profile by route of inoculation in primary infections of non-human primates with Dengue Virus 1

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Jayant V. Rajan ◽  
Michael McCracken ◽  
Caleigh Mandel-Brehm ◽  
Greg Gromowski ◽  
Simon Pollett ◽  
...  
Keyword(s):  
Dengue Virus ◽  
Phage Display ◽  
Denv Infection ◽  
Phage Library ◽  
Humoral Immune ◽  
Linear Peptide ◽  
Humoral Immune Responses ◽  
High Resolution Map ◽  
Domain Iii ◽  
Inoculation Route

AbstractNatural dengue virus (DENV) infections occur by mosquito bite but how the inoculation route affects the humoral immune response is unknown. We serologically profiled 20 non-human primates (NHP) from a prior study of DENV1 infection where animals were inoculated by mosquito (N = 10) or subcutaneous injection (N = 10). Using a comprehensive, densely tiled and highly redundant pan-flavivirus programmable phage library containing 91,562 overlapping 62 amino acid peptides, we produced a high-resolution map of linear peptide sequences enriched during DENV seroconversion. Profiles in mosquito-inoculated and subcutaneously-inoculated animals were similar up to 90 days after primary infection, but diverged at 1 year with differences in sero-reactivity in the Envelope (E; residues 215–406; p < 0.08), and Nonstructural-3 (NS3; residues 549–615; p < 0.05) proteins in mosquito-inoculated versus subcutaneously-inoculated animals. Within the E protein, residues 339–384 in domain III accounted for > 99% of the observed sero-reactivity difference. Antibody breadth did not vary by mode of inoculation. The differential reactivity to E domain III seen by phage display validated orthogonally by ELISA, but did not correlate with late neutralization titers. Serological profiling of humoral immune responses to DENV infection in NHP by programmable phage display demonstrated durable differences in sero-reactivity by route of inoculation.

scholarly journals Micafungin Inhibits Dengue Virus Infection through the Disruption of Virus Binding, Entry, and Stability

2021 ◽  
Vol 14 (4) ◽  
pp. 338
Author(s):  
Yen-Chen Chen ◽  
Jeng-Wei Lu ◽  
Chia-Tsui Yeh ◽  
Te-Yu Lin ◽  
Feng-Cheng Liu ◽  
...  
Keyword(s):  
Dengue Virus ◽  
Dengue Fever ◽  
Early Stage ◽  
Quantitative Polymerase Chain Reaction ◽  
Enterovirus 71 ◽  
Denv Infection ◽  
Immunofluorescence Assay ◽  
Dependent Manner ◽  
Virus Binding ◽  
Virus Serotype

Dengue fever is an arbovirus disease caused by infection with the dengue virus (DENV). Half of the world’s population lives under the threat of dengue fever, however, researchers have yet to develop any drugs that are clinically applicable to this infection. Micafungin is a member of the echinocandins family of anti-fungal drugs, capable of blocking the synthesis of β-1,3-D-glucan in the walls of fungal cells. Previous studies have demonstrated the effectiveness of Micafungin against infections of enterovirus 71 (EV71) and chikungunya virus (CHIKV). This is the first study demonstrating the effectiveness of micafungin in inhibiting the cytopathic effects of dengue virus serotype 2 (DENV-2) in a dose-dependent manner. Time-of-addition assays verified the inhibitory effects of micafungin in pre-treated, co-treated, and full-treatment groups. Binding and entry assays also demonstrated the effectiveness of micafungin in the early stage of DENV-2 infection. The virucidal efficacy of micafungin appears to lie in its ability to destroy the virion. Molecular docking assays revealed the binding of micafungin to the envelope protein of DENV-2, thereby revealing the mechanism by which micafungin affects the early stage of DENV infection and the stability of DENV. Two other micafungin analogs, caspofungin and anidulafungin, were also shown to have the antiviral effects on DENV-2. Finally, immunofluorescence assay (IFA) and reverse-transcription quantitative polymerase chain reaction (RT-qPCR) confirmed the broad anti-DENV ability of micafungin against dengue virus serotypes 1, 3, and 4 (DENV-1, DENV-3, and DENV-4). Taken together, these results demonstrate the potential of micafungin and its analogs as candidates for the development of broad-spectrum treatments for DENV infection.

Tetanus toxin light chain recognition by CD4+ and CD8+ human T cell clones

1995 ◽  
Vol 84 (1-2) ◽  
pp. 122-122
Author(s):  
Isabelle Kerblat ◽  
Catherine Aude ◽  
Christian Drouet ◽  
Heinet Niemann ◽  
Maurice Colomb
Keyword(s):  
T Cell ◽  
Light Chain ◽  
Tetanus Toxin ◽  
T Cell Clones ◽  
Human T Cell ◽  
Cell Clones
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