Role of endoplasmic reticulum stress-related unfolded protein response and its implications in dengue virus infection for biomarker development

Life Sciences, Journal Year: 2023, Volume and Issue: 329, P. 121982 - 121982

Published: July 28, 2023

Language: Английский

---

A Review on The Pathogenesis of Cardiovascular Disease of Flaviviridea Viruses Infection

Viruses, Journal Year: 2024, Volume and Issue: 16(3), P. 365 - 365

Published: Feb. 27, 2024

Members of the Flaviviridae family, encompassing Flavivirus and Hepacivirus genera, are implicated in a spectrum severe human pathologies. These diseases span diverse spectrum, including hepatitis, vascular shock syndrome, encephalitis, acute flaccid paralysis, adverse fetal outcomes, such as congenital heart defects increased mortality rates. Notably, infections by viruses have been associated with substantial cardiovascular compromise, yet exploration into attendant sequelae underlying mechanisms remains relatively underexplored. This review aims to explore epidemiology virus synthesize their morbidities. Leveraging current research trajectories our investigative contributions, we aspire construct cogent theoretical framework elucidating pathogenesis Flaviviridae-induced injury illuminate prospective therapeutic avenues.

Language: Английский

---

Dengue, West Nile, and Zika Viruses: Potential Novel Antiviral Biologics Drugs Currently at Discovery and Preclinical Development Stages

Pharmaceutics, Journal Year: 2022, Volume and Issue: 14(11), P. 2535 - 2535

Published: Nov. 20, 2022

Dengue, West Nile and Zika viruses are vector-borne flaviviruses responsible for numerous disease outbreaks in both Hemispheres. Despite relatively low mortality, infection may lead to potentially severe situations such as (depending on the virus): hypovolemic shock, encephalitis, acute flaccid paralysis, Guillain-Barré syndrome, congenital malformations (e.g., microcephaly) and, some situations, death. Moreover, also have major socioeconomic repercussions, especially already vulnerable societies. Thus far, only generic symptoms relief is possible, there no specific treatments available yet. Dengvaxia was world’s first dengue vaccine. However, it not fully effective. Prophylactic approaches against even more limited. Therefore, therapeutic strategies required will be discussed hereafter. We briefly present these viruses’ epidemiology, life cycle structure. Then, we introduce clinical presentation, diagnosis vaccines. Finally, list discuss promising compounds at discovery preclinical development stages deposited GlobalData database divided into three main types, according molecule: antibody-based, peptide-based molecules other compounds. To conclude, compare developments, useful future therapies of concern human health.

Language: Английский

---

ISG15 driven cellular responses to virus infection

Biochemical Society Transactions, Journal Year: 2022, Volume and Issue: 50(6), P. 1837 - 1846

Published: Nov. 23, 2022

One of the hallmarks antiviral responses to infection is production interferons and subsequently interferon stimulated genes. Interferon gene 15 (ISG15) among earliest most abundant proteins induced upon signalling, encompassing versatile functions in host immunity. ISG15 a ubiquitin like modifier that can be conjugated substrates process analogous ubiquitylation referred as ISGylation. The free unconjugated form either exist intracellularly or secreted function cytokine. Interestingly, has been reported both advantageous detrimental development immunopathology during infection. This review describes recent findings on role human models, with particular emphasis autophagy, inflammatory cellular metabolism combined viral strategies counteracting them. field ISGylation steadily gained momentum; however much previous studies virus infections conducted mouse models are sharp contrast cells, underscoring need summarise our current understanding its potential humans identify knowledge gaps which addressed future studies.

Language: Английский

---

Suspected tick‐borne flavivirus meningoencephalomyelitis in dogs from the UK: six cases (2021)

Journal of Small Animal Practice, Journal Year: 2023, Volume and Issue: 65(2), P. 132 - 143

Published: Nov. 13, 2023

Objectives Tick‐borne encephalitis virus and louping ill are neurotropic flaviviruses transmitted by ticks. Epidemiologically, tick‐borne is endemic in Europe whereas ill's predominant geographical distribution the UK. Rarely, these affect dogs causing neurological signs. This case series aimed to describe clinical, clinicopathological, imaging findings, as well outcomes six with meningoencephalitis and/or meningomyelitis caused a flavivirus UK 2021. Materials Methods Observational retrospective case‐series study. Clinical data were retrieved from medical records of positive serological or immunohistochemical results three different institutions spring winter Results Six included All presented an initial phase pyrexia lethargy followed progressive signs spinal cord intracranial disease. Magnetic resonance showed bilateral symmetrical lesions affecting grey matter thalamus, pons, medulla oblongata, thoracic lumbar intumescences none mild parenchymal meningeal contrast enhancement. Serology for was five presence seroconversion two dogs. The viral distinction between not achieved. One dog negative serology immunohistochemistry at post‐mortem examination. Three survived but sequelae. euthanased due rapid progression clinical static Significance These cases raise awareness emergent disease increased prevalence

Language: Английский

---

Usp25-Erlin1/2 activity limits cholesterol flux to restrict virus infection

Developmental Cell, Journal Year: 2023, Volume and Issue: 58(22), P. 2495 - 2509.e6

Published: Sept. 7, 2023

Reprogramming lipid metabolic pathways is a critical feature of activating immune responses to infection. However, how these reconfigurations occur poorly understood. Our previous screen identify cellular deubiquitylases (DUBs) activated during influenza virus infection revealed Usp25 as prominent hit. Here, we show that Usp25-deleted human lung epithelial A549 cells display >10-fold increase in pathogenic production, which was rescued upon reconstitution with the wild type but not catalytically deficient (C178S) variant. Proteomic analysis interactors strong association Erlin1/2, confirmed its substrate. Newly synthesized Erlin1/2 were degraded

Language: Английский

---

Cross-Neutralizing Anti-Chikungunya and Anti-Dengue 2 IgG Antibodies from Patients and BALB/c Mice against Dengue and Chikungunya Viruses

Viruses, Journal Year: 2024, Volume and Issue: 16(7), P. 1098 - 1098

Published: July 8, 2024

Dengue (DENV) and Chikungunya (CHIKV) viruses can be transmitted simultaneously by Aedes mosquitoes, there may co-infections in humans. However, how the adaptive immune response is modified host has yet to known entirely. In this study, we analyzed cross-reactivity neutralizing activity of IgG antibodies against DENV CHIKV sera patients from Mexican Institute Social Security Veracruz, Mexico, collected 2013 2015 using BALB/c mice inoculated with and/or CHIKV. Mice first then produced that neutralized both viruses. were CHIKV, DENV; they had more significant anti-CHIKV antibody activity. inoculation only resulted better neutralization DENV2. obtained 2013, low observed. CHIKV-positive sera, anti-DENV was high. These results suggest stimulates DENV2-induced memory responses vice versa. Furthermore, between two generated antibodies, but exchanging for DENV2 a response.

Language: Английский

---

DDX3 regulates the cap-independent translation of the Japanese encephalitis virus via its interactions with PABP1 and the untranslated regions of the viral genome

Published: Jan. 6, 2025

The translation of global cellular proteins is almost completely repressed in cells with flavivirus infection, while viral remains efficient. mechanisms flaviviruses evade host translational shutoff are largely unknown. Here, we identified elements and factors associated JEV evasion shutoff. 5′UTR lacked IRES or IRES-like activity, noncapped initiated the presence 3′UTR. Furthermore, DB2 sHP-SL within 3′UTR were involved regulation cap-independent translation, which conserved genus Orthoflavivirus . By RNA affinity purification mass spectrometry analysis, DDX3 PABP1 as key regulating via their interactions structures. Mechanistically, revealed that could bind to both genome establish a closed-loop architecture, recruit eIF4G/eIF4A form DDX3/PABP1/eIF4G/eIF4A tetrameric complex its interaction PABP1, thereby recruiting 43S PIC 5′-end start translation. Our findings demonstrated noncanonical strategy employed by further regulatory roles this mechanism. These results expand our knowledge initiation under state shutoff, provides antiviral target against orthoflavivirus

Language: Английский

---

DDX3 regulates the cap-independent translation of the Japanese encephalitis virus via its interactions with PABP1 and the untranslated regions of the viral genome

Published: Jan. 6, 2025

The translation of global cellular proteins is almost completely repressed in cells with flavivirus infection, while viral remains efficient. mechanisms flaviviruses evade host translational shutoff are largely unknown. Here, we identified elements and factors associated JEV evasion shutoff. 5′UTR lacked IRES or IRES-like activity, noncapped initiated the presence 3′UTR. Furthermore, DB2 sHP-SL within 3′UTR were involved regulation cap-independent translation, which conserved genus Orthoflavivirus . By RNA affinity purification mass spectrometry analysis, DDX3 PABP1 as key regulating via their interactions structures. Mechanistically, revealed that could bind to both genome establish a closed-loop architecture, recruit eIF4G/eIF4A form DDX3/PABP1/eIF4G/eIF4A tetrameric complex its interaction PABP1, thereby recruiting 43S PIC 5′-end start translation. Our findings demonstrated noncanonical strategy employed by further regulatory roles this mechanism. These results expand our knowledge initiation under state shutoff, provides antiviral target against orthoflavivirus

Language: Английский

---

Transient Expression of Zika NS2B Protein Antigen in Nicotiana benthamiana and Use for Arboviruses Diagnosis

ACS Omega, Journal Year: 2025, Volume and Issue: 10(2), P. 2184 - 2196

Published: Jan. 8, 2025

Zika (ZIKV) and Dengue (DENV) viruses are clinically significant due to their severe neurological hemorrhagic complications. Rapid diagnostics often rely on nonstructural proteins generate specific antibodies. This study aimed produce IgG antibodies from the recombinant ZIKV protein plant-expressed NS2B for arbovirus detection in serum urine samples. The was expressed Nicotiana benthamiana purified chromatographically. Validation of as an antigen indirect immunoassays demonstrated 95% sensitivity 100% specificity IgM/IgG ELISA tests, enabling effective DENV. Notably, r-ZIKV-NS2B identified positive DENV cases but failed detect negatives, suggesting limitations diagnostics. Using a diagnostic medium offers less invasive more practical approach, broadening test applicability. utilized patient-derived samples healthy spiked with exogenous virus. Findings highlight potential ZIKV-NS2B robust diagnosis demonstrate viability plant-based systems production, advancing neglected tropical diseases.

Language: Английский

---