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New Microbes and New Infections 2024
PubMed: 38818244
DOI: 10.1016/j.nmni.2024.101431 -
Heliyon May 2024The roles of antibodies secreted by subsets of B cells in dengue virus (DENV) infection have been extensively studied, yet, the contribution of tissue-homing B cells to...
The roles of antibodies secreted by subsets of B cells in dengue virus (DENV) infection have been extensively studied, yet, the contribution of tissue-homing B cells to antiviral immunity remains unclear. In this study, we performed a comprehensive analysis of B cell subpopulations in peripheral blood samples from DENV-infected patients using single-cell RNA-sequencing (scRNA-seq) datasets and flow cytometry. We showed that plasma cells (PCs) and plasmablasts (PBs) were the predominant B cell populations during the acute phase of secondary natural DENV infection, but not in convalescent phase nor in healthy controls. Interestingly, these cells expressed proliferation, adhesion, and tissue-homing genes, including , a homing marker of the skin, the initial infected site of DENV. Flow cytometry analysis confirmed a significant upregulation of cell surface expression of a cutaneous lymphocyte-associated antigen (CLA) encoded by in PCs and PBs, compared to naive and memory B cells from the same patients. The analysis of an independent single-cell B-cell receptor sequencing (scBCR-seq) dataset of DENV-infected patients revealed that the peripheral blood PCs and PBs exhibited the highest clonal expansion in secondary DENV infection compared to other B cell subsets. These clonally expanded cells also expressed the highest levels of tissue-homing genes, including In addition, by utilizing a public scRNA-seq dataset of SARS-CoV2 infection, we demonstrated the upregulation of several tissue-homing genes in PCs and PBs. Our study provides evidence for the potential roles of tissue-homing B cell subsets in the context of immune responses against viral infections in humans.
PubMed: 38818157
DOI: 10.1016/j.heliyon.2024.e30314 -
PNAS Nexus May 2024C-type lectins (CTLs) are a family of carbohydrate-binding proteins and an important component of mosquito saliva. Although CTLs play key roles in immune activation and...
C-type lectins (CTLs) are a family of carbohydrate-binding proteins and an important component of mosquito saliva. Although CTLs play key roles in immune activation and viral pathogenesis, little is known about their role in regulating dengue virus (DENV) infection and transmission. In this study, we established a homozygous knockout mutant line using CRISPR/Cas9 to study the interaction between and viruses in mosquito vectors. Furthermore, mouse experiments were conducted to confirm the transmission of DENV by mutants. We found that was mainly expressed in the medial lobe of the salivary glands (SGs) in female . knockout increased DENV replication and accumulation in the SGs of female , suggesting that plays an important role in DENV transmission. We also found a reduced expression of immunodeficiency and Janus kinase/signal transducer and activator of transcription pathway components correlated with increased DENV viral titer, infection rate, and transmission efficiency in the mutant strain. The findings of this study provide insights not only for guiding future investigations on the influence of CTLs on immune responses in mosquitoes but also for developing novel mutants that can be used as vector control tools.
PubMed: 38813522
DOI: 10.1093/pnasnexus/pgae188 -
Health Science Reports Jun 2024Epidemics of the dengue virus can trigger widespread morbidity and mortality along with no specific treatment. Examining the spatial autocorrelation and variability of...
BACKGROUND
Epidemics of the dengue virus can trigger widespread morbidity and mortality along with no specific treatment. Examining the spatial autocorrelation and variability of dengue prevalence throughout Bangladesh's 64 districts was the focus of this study.
METHODS
The spatial autocorrelation is evaluated with the help of Moran and Geary . Local Moran was used to detect hotspots and cold spots, whereas local Getis Ord was used to identify only spatial hotspots. The spatial heterogeneity has been detected using various conventional and spatial models, including the Poisson-Gamma model, the Poisson-Lognormal Model, the Conditional Autoregressive (CAR) model, the Convolution model, and the BYM2 model, respectively. These models are implemented using Gibbs sampling and other Bayesian hierarchical approaches to analyze the posterior distribution effectively, enabling inference within a Bayesian context.
RESULTS
The study's findings show that Moran and Geary analysis provides a substantial clustering pattern of positive spatial autocorrelation of dengue fever (DF) rates between surrounding districts at a 90% confidence interval. The Local Indicators of Spatial Autocorrelation cluster mapped spatial clusters and outliers based on prevalence rates, while the local Getis-Ord displayed a thorough breakdown of high or low rates, omitting outliers. Although Chattogram had the most dengue cases (15,752), Khulna district had a higher prevalence rate (133.636) than Chattogram (104.796). The BYM2 model, determined to be well-fitted based on the lowest Deviance Information Criterion value (527.340), explains a significant association between spatial heterogeneity and prevalence rates.
CONCLUSION
This research pinpoints the district with the highest prevalence rate for dengue and the neighboring districts that also have high risk, allowing government agencies and communities to take the necessary precautions to mollify the risk effect of DF.
PubMed: 38812714
DOI: 10.1002/hsr2.2154 -
ACS Infectious Diseases Jun 2024Dengue virus (DENV) nonstructural protein 5 (NS5), consisting of methyltransferase and RNA-dependent RNA polymerase (RdRp) domains, is critical for viral RNA synthesis...
Dengue virus (DENV) nonstructural protein 5 (NS5), consisting of methyltransferase and RNA-dependent RNA polymerase (RdRp) domains, is critical for viral RNA synthesis within endoplasmic reticulum-derived replication complexes in the cytoplasm. However, a significant proportion of NS5 is localized to the nucleus of infected cells for DENV2, 3, and 4, whereas DENV1 NS5 is localized diffusely in the cytoplasm. We still have an incomplete understanding of how the DENV NS5 subcellular localization is regulated. Within NS5, two putative nuclear localization signal (NLS) sequences have been identified: NLS residing in the palm of the RdRp domain as well as the recently discovered NLS residing in the flexible region at the C-terminal of the RdRp domain. We have previously shown that DENV2 NS5 nuclear localization can be significantly reduced by single-point mutations to the NLS. Here, we present biochemical, virological, and structural data demonstrating that the relative importance of either NLS in NS5 nuclear localization is unique to each of the four DENV serotypes. DENV1 NS5's cytoplasmic localization appears to be due to a functionally weak interaction between its NLS and importin-α (IMPα), while DENV2 NS5 is almost exclusively nuclear through its NLS's strong interaction with IMPα. Both NLSs of DENV3 NS5 appear to contribute to directing its nuclear localization. Lastly, in the case of DENV4, the regulation of its NS5 nuclear localization remains an enigma but appears to be associated with its NLS.
Topics: Viral Nonstructural Proteins; Dengue Virus; Nuclear Localization Signals; Cell Nucleus; Humans; Serogroup; Cytoplasm; Virus Replication; RNA-Dependent RNA Polymerase; Animals; Dengue; Protein Transport
PubMed: 38811007
DOI: 10.1021/acsinfecdis.4c00054 -
Open Veterinary Journal Apr 2024Dengue infection can trigger an immunological response that results in an inflammatory reaction, which acts as a defensive mechanism to protect the host. Dengue...
BACKGROUND
Dengue infection can trigger an immunological response that results in an inflammatory reaction, which acts as a defensive mechanism to protect the host. Dengue infection leads to an elevation in the release of pro-inflammatory cytokines, including tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6). These three cytokines have been shown to correlate with the development of thrombocytopenia and plasma leakage, which is related to the severity of the disease.
AIM
This study aims to investigate the effect of faloak ( R. Br) stem bark on TNF-α, IL-1β, and IL-6 levels in Wistar rats infected with dengue, specifically DENV-3.
METHODS
A group of 27 male Wistar rats () aged 2-3 months and weighting 200-300 g were divided into three distinct groups: healthy, dengue, and treatment (dengue infection and extract) groups. The rats in both the dengue and treatment groups were administered an injection of DENV-3 with a titer of 105 pfu at a dosage of 0.8 cc via the intraperitoneal route. The propagation of DENV-3 was initiated using C6/36 cells, and it underwent four passages. The extract was administered orally via a nasogastric tube at a dosage of 1,500 mg/kg body weight once daily for 7 days. The healthy group underwent blood sampling on the first day, whereas the dengue and therapy groups underwent blood sampling on the fifth and eighth, respectively.
RESULTS
Compared with the healthy group, TNF-α levels in the dengue and treatment groups showed significant differences on day 5 post-infection. The analysis revealed a statistically significant difference between the dengue-treatment and dengue-healthy groups. The IL-1β levels in the dengue and healthy groups significantly differed on days 5 and 8 post-infection compared to the healthy group. The treatment group had less of a decrease in IL-6 levels on days 5 and 8 than the dengue group. However, no statistically significant differences were observed.
CONCLUSION
The stem bark of shows potential as an anti-inflammatory agent in dengue infections, particularly in its ability to decrease levels of TNF-α and IL-1β.
Topics: Animals; Rats, Wistar; Male; Rats; Plant Bark; Tumor Necrosis Factor-alpha; Dengue; Plant Extracts; Interleukin-6; Anti-Inflammatory Agents; Interleukin-1beta; Dengue Virus
PubMed: 38808285
DOI: 10.5455/OVJ.2024.v14.i4.11 -
Heliyon May 2024In recent years, research on exosomal miRNAs has provided new insights into exploring the mechanism of viral infection and disease prevention. This study aimed to...
BACKGROUND
In recent years, research on exosomal miRNAs has provided new insights into exploring the mechanism of viral infection and disease prevention. This study aimed to investigate the serum exosomal miRNA expression profile of dengue-infected individuals through a community survey of dengue virus (DENV) infection.
METHODS
A seroprevalence study of 1253 healthy persons was first conducted to ascertain the DENV infection status in Baiyun District, Guangzhou. A total of 18 serum samples, including 6 healthy controls (HC), 6 asymptomatic DENV infections (AsymptDI), and 6 confirmed dengue fever patients (AcuteDI), were collected for exosome isolation and then sRNA sequencing. Through bioinformatics analysis, we discovered distinct serum exosomal miRNA profiles among the different groups and identified differentially expressed miRNAs (DEMs). These findings were further validated by qRT-PCR.
RESULTS
The community survey of DENV infection indicated that the DENV IgG antibody positivity rate among the population was 11.97 % in the study area, with asymptomatic infected individuals accounting for 93.06 % of the anti-DENV IgG positives. The age and Guangzhou household registration were associated with DENV IgG antibody positivity by logistic regression analysis. Distinct miRNA profiles were observed between healthy individuals and DENV infections. A total of 1854 miRNAs were identified in 18 serum exosome samples from the initial analysis of the sequencing data. Comparative analysis revealed 23 DEMs comprising 5 upregulated and 18 downregulated miRNAs in the DENV-infected group (mergedDI). In comparison to AcuteDI, 18 upregulated miRNAs were identified in AsymptDI. Moreover, functional enrichment of the predicted target genes of DEMs indicated that these miRNAs were involved in biological processes and pathways related to cell adhesion, focal adhesion, endocytosis, and ECM-receptor interaction. Eight DEMs were validated by qRT-PCR.
CONCLUSION
The Baiyun District of Guangzhou exhibits a notable proportion of asymptomatic DENV infections as suggested in other research, highlighting the need for enhanced monitoring and screening of asymptomatic persons and the elderly. Differential miRNA expression among healthy, symptomatic and asymptomatic DENV-infected individuals suggests their potential as biomarkers for distinguishing DENV infection and offers new avenues of investigating the mechanisms underlying DENV asymptomatic infections.
PubMed: 38807894
DOI: 10.1016/j.heliyon.2024.e31546 -
Scientific Reports May 2024The Ae. albopictus mosquito has gained global attention due to its ability to transmit viruses, including the dengue and zika. Mosquito control is the only effective way...
Resistance to pyrethroids and the relationship between adult resistance and knockdown resistance (kdr) mutations in Aedes albopictus in dengue surveillance areas of Guizhou Province, China.
The Ae. albopictus mosquito has gained global attention due to its ability to transmit viruses, including the dengue and zika. Mosquito control is the only effective way to manage dengue fever, as no effective treatments or vaccines are available. Insecticides are highly effective in controlling mosquito densities, which reduces the chances of virus transmission. However, Ae. albopictus has developed resistance to pyrethroids in several provinces in China. Pyrethroids target the voltage-gated sodium channel gene (VGSC), and mutations in this gene may result in knockdown resistance (kdr). Correlation studies between resistance and mutations can assist viruses in managing Ae. albopictus, which has not been studied in Guizhou province. Nine field populations of Ae. albopictus at the larval stage were collected from Guizhou Province in 2022 and reared to F1 to F2 generations. Resistance bioassays were conducted against permethrin, beta-cypermethrin, and deltamethrin for both larvae and adults of Ae. albopictus. Kdr mutations were characterized by PCR and sequencing. Additionally, the correlation between the kdr allele and pyrethroid resistance was analyzed. All nine populations of Ae. albopictus larvae and adults were found to be resistant to three pyrethroid insecticides. One kdr mutant allele at codon 1016, one at 1532 and three at 1534 were identified with frequencies of 13.86% (V1016G), 0.53% (I1532T), 58.02% (F1534S), 11.69% (F1534C), 0.06% (F1534L) and 0.99% (F1534P), respectively. Both V1016G and F1534S mutation mosquitoes were found in all populations. The kdr mutation F1534S was positively correlated with three pyrethroid resistance phenotypes (OR > 1, P < 0.05), V1016G with deltamethrin and beta-cypermethrin resistance (OR > 1, P < 0.05) and F1534C only with beta-cypermethrin resistance (OR > 1, P < 0.05). Current susceptibility status of wild populations of Ae. albopictus to insecticides and a higher frequency of kdr mutations from dengue-monitored areas in Guizhou Province are reported in this paper. Outcomes of this study can serve as data support for further research and development of effective insecticidal interventions against Ae. albopictus populations in Guizhou Province.
Topics: Animals; Pyrethrins; Aedes; Insecticide Resistance; China; Dengue; Mutation; Insecticides; Mosquito Vectors; Larva; Voltage-Gated Sodium Channels; Mosquito Control; Nitriles
PubMed: 38806622
DOI: 10.1038/s41598-024-63138-0 -
Nature Communications May 2024Understanding how emerging infectious diseases spread within and between countries is essential to contain future pandemics. Spread to new areas requires connectivity...
Understanding how emerging infectious diseases spread within and between countries is essential to contain future pandemics. Spread to new areas requires connectivity between one or more sources and a suitable local environment, but how these two factors interact at different stages of disease emergence remains largely unknown. Further, no analytical framework exists to examine their roles. Here we develop a dynamic modelling approach for infectious diseases that explicitly models both connectivity via human movement and environmental suitability interactions. We apply it to better understand recently observed (1995-2019) patterns as well as predict past unobserved (1983-2000) and future (2020-2039) spread of dengue in Mexico and Brazil. We find that these models can accurately reconstruct long-term spread pathways, determine historical origins, and identify specific routes of invasion. We find early dengue invasion is more heavily influenced by environmental factors, resulting in patchy non-contiguous spread, while short and long-distance connectivity becomes more important in later stages. Our results have immediate practical applications for forecasting and containing the spread of dengue and emergence of new serotypes. Given current and future trends in human mobility, climate, and zoonotic spillover, understanding the interplay between connectivity and environmental suitability will be increasingly necessary to contain emerging and re-emerging pathogens.
Topics: Dengue; Humans; Brazil; Mexico; Animals; Dengue Virus; Communicable Diseases, Emerging; Environment; Human Migration; Aedes
PubMed: 38806460
DOI: 10.1038/s41467-024-48465-0 -
Morbidity and Mortality Weekly Report.... May 2024Dengue is the most prevalent mosquitoborne viral illness worldwide and is endemic in Puerto Rico. Dengue's clinical spectrum can range from mild, undifferentiated...
PROBLEM/CONDITION
Dengue is the most prevalent mosquitoborne viral illness worldwide and is endemic in Puerto Rico. Dengue's clinical spectrum can range from mild, undifferentiated febrile illness to hemorrhagic manifestations, shock, multiorgan failure, and death in severe cases. The disease presentation is nonspecific; therefore, various other illnesses (e.g., arboviral and respiratory pathogens) can cause similar clinical symptoms. Enhanced surveillance is necessary to determine disease prevalence, to characterize the epidemiology of severe disease, and to evaluate diagnostic and treatment practices to improve patient outcomes. The Sentinel Enhanced Dengue Surveillance System (SEDSS) was established to monitor trends of dengue and dengue-like acute febrile illnesses (AFIs), characterize the clinical course of disease, and serve as an early warning system for viral infections with epidemic potential.
REPORTING PERIOD
May 2012-December 2022.
DESCRIPTION OF SYSTEM
SEDSS conducts enhanced surveillance for dengue and other relevant AFIs in Puerto Rico. This report includes aggregated data collected from May 2012 through December 2022. SEDSS was launched in May 2012 with patients with AFIs from five health care facilities enrolled. The facilities included two emergency departments in tertiary acute care hospitals in the San Juan-Caguas-Guaynabo metropolitan area and Ponce, two secondary acute care hospitals in Carolina and Guayama, and one outpatient acute care clinic in Ponce. Patients arriving at any SEDSS site were eligible for enrollment if they reported having fever within the past 7 days. During the Zika epidemic (June 2016-June 2018), patients were eligible for enrollment if they had either rash and conjunctivitis, rash and arthralgia, or fever. Eligibility was expanded in April 2020 to include reported cough or shortness of breath within the past 14 days. Blood, urine, nasopharyngeal, and oropharyngeal specimens were collected at enrollment from all participants who consented. Diagnostic testing for dengue virus (DENV) serotypes 1-4, chikungunya virus, Zika virus, influenza A and B viruses, SARS-CoV-2, and five other respiratory viruses was performed by the CDC laboratory in San Juan.
RESULTS
During May 2012-December 2022, a total of 43,608 participants with diagnosed AFI were enrolled in SEDSS; a majority of participants (45.0%) were from Ponce. During the surveillance period, there were 1,432 confirmed or probable cases of dengue, 2,293 confirmed or probable cases of chikungunya, and 1,918 confirmed or probable cases of Zika. The epidemic curves of the three arboviruses indicate dengue is endemic; outbreaks of chikungunya and Zika were sporadic, with case counts peaking in late 2014 and 2016, respectively. The majority of commonly identified respiratory pathogens were influenza A virus (3,756), SARS-CoV-2 (1,586), human adenovirus (1,550), respiratory syncytial virus (1,489), influenza B virus (1,430), and human parainfluenza virus type 1 or 3 (1,401). A total of 5,502 participants had confirmed or probable arbovirus infection, 11,922 had confirmed respiratory virus infection, and 26,503 had AFI without any of the arboviruses or respiratory viruses examined.
INTERPRETATION
Dengue is endemic in Puerto Rico; however, incidence rates varied widely during the reporting period, with the last notable outbreak occurring during 2012-2013. DENV-1 was the predominant virus during the surveillance period; sporadic cases of DENV-4 also were reported. Puerto Rico experienced large outbreaks of chikungunya that peaked in 2014 and of Zika that peaked in 2016; few cases of both viruses have been reported since. Influenza A and respiratory syncytial virus seasonality patterns are distinct, with respiratory syncytial virus incidence typically reaching its annual peak a few weeks before influenza A. The emergence of SARS-CoV-2 led to a reduction in the circulation of other acute respiratory viruses.
PUBLIC HEALTH ACTION
SEDSS is the only site-based enhanced surveillance system designed to gather information on AFI cases in Puerto Rico. This report illustrates that SEDSS can be adapted to detect dengue, Zika, chikungunya, COVID-19, and influenza outbreaks, along with other seasonal acute respiratory viruses, underscoring the importance of recognizing signs and symptoms of relevant diseases and understanding transmission dynamics among these viruses. This report also describes fluctuations in disease incidence, highlighting the value of active surveillance, testing for a panel of acute respiratory viruses, and the importance of flexible and responsive surveillance systems in addressing evolving public health challenges. Various vector control strategies and vaccines are being considered or implemented in Puerto Rico, and data from ongoing trials and SEDSS might be integrated to better understand epidemiologic factors underlying transmission and risk mitigation approaches. Data from SEDSS might guide sampling strategies and implementation of future trials to prevent arbovirus transmission, particularly during the expansion of SEDSS throughout the island to improve geographic representation.
Topics: Puerto Rico; Humans; Dengue; Sentinel Surveillance; Adult; Female; Adolescent; Middle Aged; Child; Male; Child, Preschool; Young Adult; Aged; Infant
PubMed: 38805389
DOI: 10.15585/mmwr.ss7303a1