Extensive research has been conducted on the SARS-CoV-2 virus in association with various infectious diseases to understand the pathophysiology of the infection and potential co-infections. In tropical countries, exposure to local viruses may alter the course of SARS-CoV-2 infection and coinfection. Notably, only a portion of the antibodies produced against SARS-CoV-2 proteins demonstrate neutralizing properties, and the immune response following natural infection tends to be temporary. In contrast, long-lasting IgG antibodies are common after dengue virus infections. In cases where preexisting antibodies from an initial dengue virus infection bind to a different dengue serotype during a subsequent infection, there is a potential for antibody-dependent enhancement (ADE) and the formation of immune complexes associated with disease severity. Both SARS-CoV-2 and dengue infections can result in immunodeficiency. Viral proteins of both viruses interfere with the host's IFN-I signaling. Additionally, a cytokine storm can occur after viral infection, impairing a proper response, and autoantibodies against a wide array of proteins can appear during convalescence. Most of the reported autoantibodies are typically short-lived. Vaccines against both viruses alter the immune response, affecting the course of viral infection and enhancing clearance. A comprehensive analysis of both viral infections and pathogenicity is revisited to prevent infection, severity, and mortality.
- MeSH
- COVID-19 * imunologie virologie MeSH
- dengue * imunologie virologie MeSH
- koinfekce imunologie virologie MeSH
- lidé MeSH
- protilátky virové * imunologie MeSH
- SARS-CoV-2 * imunologie MeSH
- virus dengue * imunologie MeSH
- zvýšená infektivita v přítomnosti protilátek imunologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
INTRODUCTION: This work focuses on the Dengue-viremia ABC (Atangana-Baleanu Caputo) fractional-order differential equations, accounting for both symptomatic and asymptomatic infected cases. Symptomatic cases are characterized by higher viremia levels, whereas asymptomatic cases exhibit lower viremia levels. The fractional-order model highlights memory effects and other advantages over traditional models, offering a more comprehensive representation of dengue dynamics. METHODS: The total population is divided into four compartments: susceptible, asymptomatic infected, symptomatic infected, and recovered. The model incorporates an immune-boosting factor for asymptomatic infected individuals and clinical treatment for symptomatic cases. Positivity and boundedness of the model are validated, and both local and global stability analyses are performed. The novel Adams-Bash numerical scheme is utilized for simulations to rigorously assess the impact of optimal control interventions. RESULTS: The results demonstrate the effectiveness of the proposed control strategies. The reproduction numbers must be reduced based on specific optimal control conditions to effectively mitigate disease outbreaks. Numerical simulations confirm that the optimal control measures can significantly reduce the spread of the disease. DISCUSSION: This research advances the understanding of Dengue-viremia dynamics and provides valuable insights into the application of ABC fractional-order analysis. By incorporating immune-boosting and clinical treatment into the model, the study offers practical guidelines for implementing successful disease control strategies. The findings highlight the potential of using optimal control techniques in public health interventions to manage disease outbreaks more effectively.
- MeSH
- dengue * MeSH
- epidemický výskyt choroby MeSH
- lidé MeSH
- viremie * MeSH
- virus dengue imunologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
Viral infection may represent a stress condition to the host cell. Cells react to it by triggering the defence programme to restore homeostasis and these events may in turn impact the viral replication. The knowledge about tick-borne encephalitis virus (TBEV) infection-associated stress is limited. Here we investigated the interplay between TBEV infection and stress pathways in PMJ2-R mouse macrophage cell line, as macrophages are the target cells in early phases of TBEV infection. First, to determine how stress influences TBEV replication, the effect of stress inducers H2O2 and tunicamycin (TM) was tested. Viral multiplication was decreased in the presence of both stress inducers suggesting that the stress and cellular stress responses restrict the virus replication. Second, we investigated the induction of oxidative stress and endoplasmic reticulum (ER) stress upon TBEV infection. The level of oxidative stress was interrogated by measuring the reactive oxygen species (ROS). ROS were intermittently increased in infected cells at 12 hpi and at 72 hpi. As mitochondrial dysfunction may result in increased ROS level, we evaluated the mitochondrial homeostasis by measuring the mitochondrial membrane potential (MMP) and found that TBEV infection induced the hyperpolarization of MMP. Moreover, a transient increase of gene expression of stress-induced antioxidative enzymes, like p62, Gclm and Hmox1, was detected. Next, we evaluated the ER stress upon TBEV infection by analysing unfolded protein responses (UPR). We found that infection induced gene expression of two general sensors BiP and CHOP and activated the IRE1 pathway of UPR. Finally, since the natural transmission route of TBEV from its tick vector to the host is mediated via tick saliva, the impact of tick saliva from Ixodes ricinus on stress pathways in TBEV-infected cells was tested. We observed only marginal potentiation of UPR pathway. In conclusion, we found that TBEV infection of PMJ2-R cells elicits the changes in redox balance and triggers cellular stress defences, including antioxidant responses and the IRE1 pathway of UPR. Importantly, our results revealed the negative effect of stress-evoked events on TBEV replication and only marginal impact of tick saliva on stress cellular pathways.
- MeSH
- buněčné linie MeSH
- klíšťová encefalitida * MeSH
- myši MeSH
- peroxid vodíku metabolismus MeSH
- protein-serin-threoninkinasy metabolismus MeSH
- reaktivní formy kyslíku metabolismus MeSH
- replikace viru MeSH
- viry klíšťové encefalitidy * genetika MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Tick-borne encephalitis (TBE) virus (TBEV) is transmitted to humans via tick bites. Infection is benign in >90% of the cases but can cause mild (<5%), moderate (<4%), or severe (<1%) encephalitis. We show here that ∼10% of patients hospitalized for severe TBE in cohorts from Austria, Czech Republic, and France carry auto-Abs neutralizing IFN-α2, -β, and/or -ω at the onset of disease, contrasting with only ∼1% of patients with moderate and mild TBE. These auto-Abs were found in two of eight patients who died and none of 13 with silent infection. The odds ratios (OR) for severe TBE in individuals with these auto-Abs relative to those without them in the general population were 4.9 (95% CI: 1.5-15.9, P < 0.0001) for the neutralization of only 100 pg/ml IFN-α2 and/or -ω, and 20.8 (95% CI: 4.5-97.4, P < 0.0001) for the neutralization of 10 ng/ml IFN-α2 and -ω. Auto-Abs neutralizing type I IFNs accounted for ∼10% of severe TBE cases in these three European cohorts.
- MeSH
- autoprotilátky * imunologie MeSH
- dospělí MeSH
- interferon typ I * imunologie MeSH
- klíšťová encefalitida * imunologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- neutralizující protilátky * imunologie MeSH
- senioři MeSH
- viry klíšťové encefalitidy imunologie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Česká republika MeSH
- Rakousko MeSH
Tick-borne encephalitis virus (TBEV) targets the central nervous system (CNS), leading to potentially severe neurological complications. The neurovascular unit plays a fundamental role in the CNS and in the neuroinvasion of TBEV. However, the role of human brain pericytes, a key component of the neurovascular unit, during TBEV infection has not yet been elucidated. In this study, TBEV infection of the primary human brain perivascular pericytes was investigated with highly virulent Hypr strain and mildly virulent Neudoerfl strain. We used Luminex assay to measure cytokines/chemokines and growth factors. Both viral strains showed comparable replication kinetics, peaking at 3 days post infection (dpi). Intracellular viral RNA copies peaked at 6 dpi for Hypr and 3 dpi for Neudoerfl cultures. According to immunofluorescence staining, only small proportion of pericytes were infected (3% for Hypr and 2% for Neudoerfl), and no cytopathic effect was observed in the infected cells. In cell culture supernatants, IL-6 production was detected at 3 dpi, together with slight increases in IL-15 and IL-4, but IP-10, RANTES and MCP-1 were the main chemokines released after TBEV infection. These chemokines play key roles in both immune defense and immunopathology during TBE. This study suggests that pericytes are an important source of these signaling molecules during TBEV infection in the brain.
- MeSH
- chemokin CCL5 * metabolismus MeSH
- chemokin CXCL10 * metabolismus MeSH
- cytokiny metabolismus MeSH
- klíšťová encefalitida * virologie metabolismus MeSH
- kultivované buňky MeSH
- lidé MeSH
- mozek * virologie metabolismus patologie MeSH
- pericyty * virologie metabolismus MeSH
- replikace viru MeSH
- viry klíšťové encefalitidy * fyziologie patogenita MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Klíčová slova
- symptomatická léčba,
- MeSH
- hlášení nemocí MeSH
- incidence MeSH
- klíště růst a vývoj virologie MeSH
- klíšťová encefalitida * diagnóza epidemiologie komplikace prevence a kontrola MeSH
- lidé MeSH
- repelenty proti hmyzu MeSH
- vakcinace * metody MeSH
- viry klíšťové encefalitidy klasifikace patogenita MeSH
- Check Tag
- lidé MeSH
- Geografické názvy
- Česká republika MeSH
Background: Tick-borne encephalitis (TBE) is caused by the tick-borne encephalitis virus (TBEV). TBEV infection can cause symptoms of central nervous system (CNS) inflammation and result in severe consequences including death. TBE is an increasing health threat in the Czech Republic and elsewhere in Europe. In 2020, 23% of 3734 TBE cases reported to the European Centre for Disease Prevention and Control were from the Czech Republic. TBE vaccination is universally recommended in the Czech Republic, but a full analysis of TBE vaccine effectiveness (VE) in the Czech Republic has not been published. Methods: TBE is a notifiable disease in the Czech Republic with mandatory reporting of cases (i.e., laboratory-confirmed TBEV infected patient with symptoms of CNS inflammation) and vaccination history to public health authorities. TBE VE was estimated using the screening method utilizing public health surveillance data from 2018 to 2022 and online household surveys of the general population on TBE vaccine uptake conducted in 2019-2022. Results: In 2018-2022, 3648 TBE cases were reported in the Czech Republic; 98.1% (3105/3166) of TBE cases with known vaccination history were unvaccinated. Among 42,671 persons surveyed from the general population who had known TBE vaccination history, 66.5% were unvaccinated. VE against TBE was 97.6% (95% confidence interval 95.7-98.7). When stratified by age group, VE was 97.1% (88.4-99.3) in 1-15 years of age, 97.9% (95.3-99.0) in 16-59 years of age, and 96.9% (90.5-99.0) in ≥60 years of age. TBE vaccination averted an estimated 1020 TBE cases in the Czech Republic from 2018 to 2022. Conclusions: This first published study with a full analysis of TBE VE in the Czech Republic showed that vaccination was highly effective for the prevention of TBE including in children, an age group with increasing TBE disease burden. Vaccination averted hundreds of TBE cases and hospitalizations despite the relatively low compliance with TBE vaccine recommendations. To prevent additional TBE cases in the Czech Republic, enhanced efforts to increase TBE vaccine uptake are needed.
- MeSH
- dítě MeSH
- dospělí MeSH
- klíšťová encefalitida * prevence a kontrola epidemiologie MeSH
- kojenec MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- předškolní dítě MeSH
- senioři MeSH
- vakcinace * MeSH
- virové vakcíny * aplikace a dávkování MeSH
- viry klíšťové encefalitidy * imunologie MeSH
- Check Tag
- dítě MeSH
- dospělí MeSH
- kojenec MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- předškolní dítě MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Česká republika MeSH
Tick-borne encephalitis virus (TBEV) is a neurotropic orthoflavivirus responsible for severe infections of the central nervous system. Although neurons are predominantly targeted, specific involvement of microglia in pathogenesis of TBE is not yet fully understood. In this study, the susceptibility of human microglia to TBEV is investigated, focusing on productive infection and different immune responses of different viral strains. We investigated primary human microglia and two immortalized microglial cell lines exposed to three TBEV strains (Hypr, Neudörfl and 280), each differing in virulence. Our results show that all microglia cultures tested support long-term productive infections, regardless of the viral strain. In particular, immune response varied significantly with the viral strain, as shown by the differential secretion of cytokines and chemokines such as IP-10, MCP-1, IL-8 and IL-6, quantified using a Luminex 48-plex assay. The most virulent strain triggered the highest cytokine induction. Electron tomography revealed substantial ultrastructural changes in the infected microglia, despite the absence of cytopathic effects. These findings underscore the susceptibility of human microglia to TBEV and reveal strain-dependent variations in viral replication and immune responses, highlighting the complex role of microglia in TBEV-induced neuropathology and contribute to a deeper understanding of TBE pathogenesis and neuroinflammation.
- MeSH
- buněčné linie MeSH
- cytokiny * metabolismus MeSH
- klíšťová encefalitida * virologie patologie imunologie MeSH
- kultivované buňky MeSH
- lidé MeSH
- mikroglie * virologie imunologie patologie MeSH
- neurozánětlivé nemoci virologie patologie imunologie MeSH
- replikace viru MeSH
- viry klíšťové encefalitidy * patogenita fyziologie imunologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
Tick-borne encephalitis virus (TBEV) is a tick-borne flavivirus that induces severe central nervous system disorders. It has recently raised concerns due to an expanding geographical range and increasing infection rates. Existing vaccines, though effective, face low coverage rates in numerous TBEV endemic regions. Our previous work demonstrated the immunogenicity and full protection afforded by a TBEV vaccine based on virus-like particles (VLPs) produced in Leishmania tarentolae cells in immunization studies in a mouse model. In the present study, we explored the impact of adjuvants (AddaS03TM, Alhydrogel®+MPLA) and administration routes (subcutaneous, intramuscular) on the immune response. Adjuvanted groups exhibited significantly enhanced antibody responses, higher avidity, and more balanced Th1/Th2 response. IFN-γ responses depended on the adjuvant type, while antibody levels were influenced by both adjuvant and administration routes. The combination of Leishmania-derived TBEV VLPs with Alhydrogel® and MPLA via intramuscular administration emerged as a highly promising prophylactic vaccine candidate, eliciting a robust, balanced immune response with substantial neutralization potential.
- MeSH
- adjuvancia imunologická * aplikace a dávkování MeSH
- adjuvantní vakcína aplikace a dávkování MeSH
- imunogenicita vakcíny MeSH
- injekce intramuskulární MeSH
- interferon gama imunologie MeSH
- klíšťová encefalitida * prevence a kontrola imunologie MeSH
- Leishmania * imunologie MeSH
- myši inbrední BALB C MeSH
- myši MeSH
- neutralizující protilátky krev imunologie MeSH
- protilátky virové * krev imunologie MeSH
- syntetické vakcíny * imunologie aplikace a dávkování MeSH
- Th1 buňky imunologie MeSH
- virové vakcíny * imunologie aplikace a dávkování MeSH
- viry klíšťové encefalitidy * imunologie MeSH
- VLP vakcíny * imunologie aplikace a dávkování MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
