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Frontiers in Cellular and Infection... 2024Chikungunya virus (CHIKV), which causes chikungunya fever, is an arbovirus of public health concern with no approved antiviral therapies. A significant proportion of...
BACKGROUND
Chikungunya virus (CHIKV), which causes chikungunya fever, is an arbovirus of public health concern with no approved antiviral therapies. A significant proportion of patients develop chronic arthritis after an infection. Zinc and magnesium salts help the immune system respond effectively against viral infections. This study explored the antiviral potential of zinc sulphate, zinc acetate, and magnesium sulphate against CHIKV infection.
METHODS
The highest non-toxic concentration of the salts (100 µM) was used to assess the prophylactic, virucidal, and therapeutic anti-CHIKV activities. Dose-dependent antiviral effects were investigated to find out the 50% inhibitory concentration of the salts. Entry bypass assay was conducted to find out whether the salts affect virus entry or post entry stages. Virus output in all these experiments was estimated using a focus-forming unit assay, real-time RT-PCR, and immunofluorescence assay.
RESULTS
Different time- and temperature-dependent assays revealed the therapeutic antiviral activity of zinc and magnesium salts against CHIKV. A minimum exposure of 4 hours and treatment initiation within 1 to 2 hours of infection are required for inhibition of CHIKV. Entry assays revealed that zinc salt affected virus-entry. Entry bypass assays suggested that both salts affected post-entry stages of CHIKV. In infected C57BL6 mice orally fed with zinc and magnesium salts, a reduction in viral RNA copy number was observed.
CONCLUSION
The study results suggest zinc salts exert anti-CHIKV activity at entry and post entry stages of the virus life cycle, while magnesium salt affect CHIKV at post entry stages. Overall, the study highlights the significant antiviral potential of zinc sulphate, zinc acetate, and magnesium sulphate against CHIKV, which can be exploited in designing potential therapeutic strategies for early treatment of chikungunya patients, thereby reducing the virus-associated persistent arthritis.
Topics: Chikungunya virus; Animals; Antiviral Agents; Chikungunya Fever; Zinc Acetate; Zinc Sulfate; Chlorocebus aethiops; Vero Cells; Virus Internalization; Mice; Zinc; Humans; Magnesium Sulfate; Magnesium; Virus Replication; Inhibitory Concentration 50; Salts; Cell Line
PubMed: 38895735
DOI: 10.3389/fcimb.2024.1335189 -
BioRxiv : the Preprint Server For... Jun 2024The mosquito is a prominent vector for arboviruses, but the breadth of mosquito viruses that infects this specie is not fully understood. In the broadest global survey...
The mosquito is a prominent vector for arboviruses, but the breadth of mosquito viruses that infects this specie is not fully understood. In the broadest global survey to date of over 200 small RNA samples, we detected viral small interfering RNAs (siRNAs) and Piwi interacting RNAs (piRNAs) arising from mosquito viruses. We confirmed that most academic laboratory colonies of lack persisting viruses, yet two commercial strains were infected by a novel tombus-like virus. from North to South American locations were also teeming with multiple insect viruses, with Anphevirus and a bunyavirus displaying geographical boundaries from the viral small RNA patterns. Asian small RNA patterns indicate infections by similar mosquito viruses from the Americas and reveal the first wild example of dengue virus infection generating viral small RNAs. African also contained various viral small RNAs including novel viruses only found in these African substrains. Intriguingly, viral long RNA patterns can differ from small RNA patterns, indicative of viral transcripts evading the mosquitoes' RNA interference (RNAi) machinery. To determine whether the viruses we discovered via small RNA sequencing were replicating and transmissible, we infected C6/36 and Aag2 cells with homogenates. Through blind passaging, we generated cell lines stably infected by these mosquito viruses which then generated abundant viral siRNAs and piRNAs that resemble the native mosquito viral small RNA patterns. This mosquito small RNA genomics approach augments surveillance approaches for emerging infectious diseases.
PubMed: 38895463
DOI: 10.1101/2024.06.06.597482 -
BioRxiv : the Preprint Server For... Jun 2024transmitted arboviral human cases are increasing worldwide and spreading to new areas of the United States of America (USA). These diseases continue to re-emerge likely...
transmitted arboviral human cases are increasing worldwide and spreading to new areas of the United States of America (USA). These diseases continue to re-emerge likely due to changes in vector ecology, urbanization, human migration, and larger range of climatic suitability. Recent shifts in landscape and weather variables are predicted to impact the habitat patterns of urban mosquitoes such as and . Miami (FL) is in the tropical zone and an established hotspot for arboviruses, while Charleston (SC) is in the humid subtropical zone and newly vulnerable. Although these coastal cities have distinct climates, both have hot summers. To understand mosquito infestation in both cities and potentiate our surveillance effort, we performed egg collections in the warmest season. We applied remote sensing with land-use cover and weather variation to identify mosquito infestation patterns. Our study found predominant occurrence of and, to a lesser extent, in both cities. We detected statistically significant positive and negative associations between entomological indicators and most weather variables in combined data from both cities. For all entomological indices, weekly wind speed and relative humidity were significantly positively associated, while precipitation and maximum temperature were significantly negatively associated. egg abundance was significantly positively associated with open land in Charleston but was negatively associated with vegetation cover in combined data. There is a clear need for further observational studies to determine the impact of climate change on and infestation in the Southeastern region of the USA.
PubMed: 38895389
DOI: 10.1101/2024.06.06.597792 -
Biological Procedures Online Jun 2024Culex pipiens L. is a principal vector of zoonotic arboviruses in Europe, acting in both an amplification role in enzootic transmission between avian hosts and as a...
BACKGROUND
Culex pipiens L. is a principal vector of zoonotic arboviruses in Europe, acting in both an amplification role in enzootic transmission between avian hosts and as a bridge vector between avian hosts and mammals. The species consists of two forms which are indistinguishable using morphological methods but possess varying ecological and physiological traits that influence their vector capacity. In this study we validate methods that can be used to extract trace DNA from single pupal exuviae of Cx. pipiens for use in molecular speciation of samples. These DNA extraction methods are compared using measurement of the total yield and successful identification using a real-time polymerase chain reaction (PCR) assay.
RESULTS
Genomic DNA was initially extracted from colony-derived individuals using an ethanol precipitation method, two commercially available DNA extraction kits: DNeasy® Blood & Tissue Kit (Qiagen, UK) and Wizard® SV Genomic DNA Purification System (Promega, UK) and a direct real-time PCR method. Time elapsed between eclosion and processing of pupae significantly influenced Cx. pipiens form identification as nucleic acid concentration and PCR amplification success decreased with increased time elapsed. Real-time PCR amplification success, however, was not shown to vary significantly between the three extraction methods, with all methods successfully identifying all samples, but the direct real-time PCR method achieved a lesser amplification success rate of 70% (n = 20 for each treatment). More variable results were produced when field-derived exuviae were used, with no significant difference in real-time PCR amplification success found across the four methods and a lower overall rate of successful identification of 55-80%.
CONCLUSIONS
This study shows that both colony and field derived Cx. pipiens pupal exuviae can be a useful non-invasive source of trace DNA permitting accurate biotype differentiation for at least twenty-four hours post-eclosion. The significance and utility of this technique in ecological and behavioural studies of Cx. pipiens is discussed and recommendations made for use according to experimental scenario.
PubMed: 38890570
DOI: 10.1186/s12575-024-00246-1 -
Parasites & Vectors Jun 2024In recent years the Asian bush mosquito Aedes japonicus has invaded Europe, including the Netherlands. This species is a known vector for a range of arboviruses,...
BACKGROUND
In recent years the Asian bush mosquito Aedes japonicus has invaded Europe, including the Netherlands. This species is a known vector for a range of arboviruses, possibly including West Nile virus (WNV). As WNV emerged in the Netherlands in 2020, it is important to investigate the vectorial capacity of mosquito species present in the Netherlands to estimate the risk of future outbreaks and further spread of the virus. Therefore, this study evaluates the potential role of Ae. japonicus in WNV transmission and spillover from birds to dead-end hosts in the Netherlands.
METHODS
We conducted human landing collections in allotment gardens (Lelystad, the Netherlands) in June, August and September 2021 to study the diurnal and seasonal host-seeking behaviour of Ae. japonicus. Furthermore, their host preference in relation to birds using live chicken-baited traps was investigated. Vector competence of field-collected Ae. japonicus mosquitoes for two isolates of WNV at two different temperatures was determined. Based on the data generated from these studies, we developed a Susceptible-Exposed-Infectious-Recovered (SEIR) model to calculate the risk of WNV spillover from birds to humans via Ae. japonicus, under the condition that the virus is introduced and circulates in an enzootic cycle in a given area.
RESULTS
Our results show that Ae. japonicus mosquitoes are actively host seeking throughout the day, with peaks in activity in the morning and evening. Their abundance in August was higher than in June and September. For the host-preference experiment, we documented a small number of mosquitoes feeding on birds: only six blood-fed females were caught over 4 full days of sampling. Finally, our vector competence experiments with Ae. japonicus compared to its natural vector Culex pipiens showed a higher infection and transmission rate when infected with a local, Dutch, WNV isolate compared to a Greek isolate of the virus. Interestingly, we also found a small number of infected Cx. pipiens males with virus-positive leg and saliva samples.
CONCLUSIONS
Combining the field and laboratory derived data, our model predicts that Ae. japonicus could act as a spillover vector for WNV and could be responsible for a high initial invasion risk of WNV when present in large numbers.
Topics: Animals; Aedes; Netherlands; Mosquito Vectors; West Nile virus; West Nile Fever; Humans; Female; Birds; Chickens; Host-Seeking Behavior; Seasons
PubMed: 38886805
DOI: 10.1186/s13071-024-06279-5 -
Acta Tropica Jun 2024The Orthoflavivirus ilheusense (ILHV) is an arbovirus that was first isolated in Brazil in 1944 during an epidemiologic investigation of yellow fever. Is a member of the...
The Orthoflavivirus ilheusense (ILHV) is an arbovirus that was first isolated in Brazil in 1944 during an epidemiologic investigation of yellow fever. Is a member of the Flaviviridae family and it belongs to the antigenic complex of the Ntaya virus group. Psorophora ferox is the primary vector of ILHV and this study presents the isolation and phylogenetic analysis of ILHV in a pool of Ps. ferox collected in the state of Goiás in 2021. Viral isolation tests were performed on Vero cells and C6/36 clones. The indirect immunofluorescence test (IFI) was used to confirm the positivity of the sample. The positive sample underwent RT-qPCR, sequencing, and phylogenetic analysis. This is the first report of ILHV circulation in this municipality and presented close relationship between this isolate and another ILHV isolate collected in the city of Belém (PA).
PubMed: 38885823
DOI: 10.1016/j.actatropica.2024.107272 -
Infectious Diseases Now Jun 2024Chikungunya disease typically presents with the fever-arthralgia-rash symptom triad. However, an increase in the number of atypical clinical manifestations, particularly... (Review)
Review
Chikungunya disease typically presents with the fever-arthralgia-rash symptom triad. However, an increase in the number of atypical clinical manifestations, particularly neurological disorders, has occurred. The current evidence regarding the pooled prevalence of Chikungunya virus (CHIKV)-associated neurological cases (CANCs) suspected of having an arboviral aetiology is not well-understood. Therefore, this meta-analysis included 19 studies (n = 7319 patients) and aimed to determine the pooled rate of exposure to CANC. The pooled positivity rate of CANC was 12 % (95 % CI: 6-19), and Brazil was overrepresented (11/19). These estimations varied between 3 and 14 % based on the diagnostic method (real-time PCR vs. ELISA-IgM) and biological samples (cerebrospinal fluid or blood specimens) used for detection of CHIKV. Regarding the frequency of CHIKV in neurological clinical subgroups, the rates were higher among patients with myelitis (27 %), acute disseminated encephalomyelitis (27 %), Guillain-Barré syndrome (15 %), encephalitis (12 %), and meningoencephalitis (7 %). Our analysis highlights the significant burden of CANC. However, the data must be interpreted with caution due to the heterogeneity of the results, which may be related to the location of the studies covering endemic periods and/or outbreaks of CHIKV. Current surveillance resources should also focus on better characterizing the epidemiology of CHIKV infection in neurological disorders. Additionally, future studies should investigate the interactions between CHIKV and neurological diseases with the aim of gaining deeper insight into the mechanisms underlying the cause-and-effect relationship between these two phenomena.
PubMed: 38885813
DOI: 10.1016/j.idnow.2024.104938 -
PLoS Pathogens Jun 2024The obligate endosymbiont Wolbachia induces pathogen interference in the primary disease vector Aedes aegypti, facilitating the utilization of Wolbachia-based mosquito...
The obligate endosymbiont Wolbachia induces pathogen interference in the primary disease vector Aedes aegypti, facilitating the utilization of Wolbachia-based mosquito control for arbovirus prevention, particularly against dengue virus (DENV). However, the mechanisms underlying Wolbachia-mediated virus blockade have not been fully elucidated. Here, we report that Wolbachia activates the host cytoplasmic miRNA biogenesis pathway to suppress DENV infection. Through the suppression of the long noncoding RNA aae-lnc-2268 by Wolbachia wAlbB, aae-miR-34-3p, a miRNA upregulated by the Wolbachia strains wAlbB and wMelPop, promoted the expression of the antiviral effector defensin and cecropin genes through the Toll pathway regulator MyD88. Notably, anti-DENV resistance induced by Wolbachia can be further enhanced, with the potential to achieve complete virus blockade by increasing the expression of aae-miR-34-3p in Ae. aegypti. Furthermore, the downregulation of aae-miR-34-3p compromised Wolbachia-mediated virus blockade. These findings reveal a novel mechanism by which Wolbachia establishes crosstalk between the cytoplasmic miRNA pathway and the Toll pathway via aae-miR-34-3p to strengthen antiviral immune responses against DENV. Our results will aid in the advancement of Wolbachia for arbovirus control by enhancing its virus-blocking efficiency.
Topics: Wolbachia; Aedes; Animals; MicroRNAs; Dengue Virus; Dengue; Toll-Like Receptors; Mosquito Vectors; Signal Transduction; RNA, Long Noncoding; Immunity, Innate; Symbiosis
PubMed: 38885278
DOI: 10.1371/journal.ppat.1012296 -
Bioorganic & Medicinal Chemistry Jul 2024This perspective underscores the rising challenge posed by emerging diseases against the backdrop of modern advancements in global public health understanding. It... (Review)
Review
This perspective underscores the rising challenge posed by emerging diseases against the backdrop of modern advancements in global public health understanding. It particularly highlights the emergence of the Oropouche virus (OROV) as a significant global threat, detailing its transmission dynamics, symptoms, and epidemiological impact, with a focus on its historical and current manifestations. It further delves into the molecular aspects of OROV, elucidating its unique characteristics, lack of structural similarity with other arboviruses, and the limited progress in medicinal chemistry research. Still, it highlights notable studies on potential antiviral agents and the challenges in drug development, emphasizing the need for innovative approaches such as structure-based drug design (SBDD) and drug repurposing. Finally, it concludes with a call to action, urging increased attention and research focus on OROV to prevent potential future pandemics fueled by viral mutations.
Topics: Antiviral Agents; Humans; Orthobunyavirus; Bunyaviridae Infections; Animals; Molecular Structure
PubMed: 38879995
DOI: 10.1016/j.bmc.2024.117797 -
Environmental Science and Pollution... Jun 2024Pyriproxyfen (PPF), Bacillus thuringiensis israelensis (BTI), and malathion (MLT) are widely used worldwide to control the population of mosquitos that transmit...
Assessment of toxicity of pyriproxyfen, Bacillus thuringiensis, and malathion and their mixtures used for mosquito control on embryo-larval development and behavior of zebrafish.
Pyriproxyfen (PPF), Bacillus thuringiensis israelensis (BTI), and malathion (MLT) are widely used worldwide to control the population of mosquitos that transmit arboviruses. The current work aimed to evaluate the toxicity of these single pesticides and their binary mixtures of PPF + BTI, PPF + MLT, and MLT + BTI on the embryo-larval stage of zebrafish (Danio rerio) as an animal model. Epiboly, mortality, apical endpoints, affected animals, heart rate, morphometric, thigmotaxis, touch sensitivity, and optomotor response tests were evaluated. PPF and MLT and all mixtures reduced the epiboly percentage. Mortality increased significantly in all exposed groups, except BTI, with MLT being the most toxic. The observed apical endpoints were pericardial and yolk sac edemas, and tail and spine deformation. Exposure to MLT showed a higher percentage of affected animals. A reduction in heart rate was also observed in MLT- and PPF + MLT-exposed groups. The PPF + MLT mixture decreased head measurements. Behavioral alterations were observed, with a decrease in thigmotaxis and touch sensitivity responses in PPF + MLT and MLT + BTI groups. Finally, optomotor responses were affected in all groups. The above data obtained suggest that the MLT + PFF mixture has the greatest toxicity effects. This mixture affected embryo-larval development and behavior and is close to the reality in several cities that use both pesticides for mosquito control rather than single pesticides, leading to a reevaluation of the strategy for mosquito control.
PubMed: 38874756
DOI: 10.1007/s11356-024-33955-x