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Euro Surveillance : Bulletin Europeen... Jun 2024Oropouche fever is caused by Oropouche virus (OROV), transmitted primarily through the bite of infected midges, particularly of the genus . The virus is mainly...
Oropouche fever is caused by Oropouche virus (OROV), transmitted primarily through the bite of infected midges, particularly of the genus . The virus is mainly circulating in Central and South America where several countries reported an ongoing outbreak. We report here two imported cases of OROV infection identified in Italy, late May-early June 2024. These cases indicate that in the shadow of a massive dengue outbreak in the Americas, the Oropouche outbreak might be more widespread than previously estimated.
Topics: Humans; Italy; Travel; Male; Cuba; Adult; Orthobunyavirus; Animals; Disease Outbreaks; Bunyaviridae Infections; Middle Aged; Female
PubMed: 38940002
DOI: 10.2807/1560-7917.ES.2024.29.26.2400362 -
Journal of Medical Virology Jun 2024COVID-19 tended to be less aggressive in dengue endemic regions. Conversely, dengue cases plummeted in dengue endemic zones during the active years of the pandemic...
COVID-19 tended to be less aggressive in dengue endemic regions. Conversely, dengue cases plummeted in dengue endemic zones during the active years of the pandemic (2020-2021). We and others have demonstrated serological cross-reactivity between these two viruses of different families. We further demonstrated that COVID-19 serum samples that were cross-reactive in dengue virus (DV) serological tests, "cross-neutralized" all DV serotypes in Huh7 cells. Here we showed by co-immunoprecipitation (Co-IP) and atomic force microscopy (AFM) imaging that severe acute respiratory syndrome (SARS)-coronavirus (CoV)-2 (SARS-CoV-2) spike (S) protein subunit S1 and S2 monoclonal antibodies can indeed, bind to DV particles. Likewise, DV envelope antibodies (DV E Abs) showed high docking frequency with other human pathogenic beta-CoVs and murine hepatitis virus-1 (MHV-1). SARS-CoV-2 Ab didn't show docking or Co-IP with MHV-1 supporting poor cross-protection among CoVs. DV E Abs showed binding to MHV-1 (AFM, Co-IP, and immunofluorescence) and prepandemic dengue patients' serum samples even "cross-neutralized" MHV-1 plaques in cell culture. Furthermore, dengue serum samples showed marked inhibition potential in a surrogate virus-based competitive enzyme-linked immunosorbent assay, used for determining neutralizing Abs against SARS-CoV-2 S protein receptor-binding domain in COVID-19 serum samples. We therefore, provide multiple evidence as to why CoVs are epidemiologically less prevalent in highly dengue endemic regions globally.
Topics: Dengue Virus; Humans; Dengue; Cross Reactions; Antibodies, Viral; SARS-CoV-2; Spike Glycoprotein, Coronavirus; COVID-19; Antibodies, Neutralizing; Animals; Antibodies, Monoclonal; Endemic Diseases
PubMed: 38932494
DOI: 10.1002/jmv.29771 -
Vaccines Jun 2024T help (Th), stimulation of toll-like receptors (pathogen-associated molecular patterns, PAMPs), and antigen organization and repetitiveness (pathogen-associated...
Identifying Key Drivers of Efficient B Cell Responses: On the Role of T Help, Antigen-Organization, and Toll-like Receptor Stimulation for Generating a Neutralizing Anti-Dengue Virus Response.
T help (Th), stimulation of toll-like receptors (pathogen-associated molecular patterns, PAMPs), and antigen organization and repetitiveness (pathogen-associated structural patterns, PASPs) were shown numerous times to be important in driving B-cell and antibody responses. In this study, we dissected the individual contributions of these parameters using newly developed "Immune-tag" technology. As model antigens, we used eGFP and the third domain of the dengue virus 1 envelope protein (DV1 EDIII), the major target of virus-neutralizing antibodies. The respective proteins were expressed alone or genetically fused to the N-terminal fragment of the cucumber mosaic virus (CMV) capsid protein-nCMV, rendering the antigens oligomeric. In a step-by-step manner, RNA was attached as a PAMP, and/or a universal Th-cell epitope was genetically added for additional Th. Finally, a PASP was added to the constructs by displaying the antigens highly organized and repetitively on the surface of CMV-derived virus-like particles (CuMV VLPs). Sera from immunized mice demonstrated that each component contributed stepwise to the immunogenicity of both proteins. All components combined in the CuMV VLP platform induced by far the highest antibody responses. In addition, the DV1 EDIII induced high levels of DENV-1-neutralizing antibodies only if displayed on VLPs. Thus, combining multiple cues typically associated with viruses results in optimal antibody responses.
PubMed: 38932390
DOI: 10.3390/vaccines12060661 -
Vaccines May 2024The dengue virus, the primary cause of dengue fever, dengue hemorrhagic fever, and dengue shock syndrome, is the most widespread mosquito-borne virus worldwide. In...
The dengue virus, the primary cause of dengue fever, dengue hemorrhagic fever, and dengue shock syndrome, is the most widespread mosquito-borne virus worldwide. In recent decades, the prevalence of dengue fever has increased markedly, presenting substantial public health challenges. Consequently, the development of an efficacious vaccine against dengue remains a critical goal for mitigating its spread. Our research utilized Celcradle™, an innovative tidal bioreactor optimized for high-density cell cultures, to grow Vero cells for dengue virus production. By maintaining optimal pH levels (7.0 to 7.4) and glucose concentrations (1.5 g/L to 3.5 g/L) during the proliferation of cells and viruses, we achieved a peak Vero cell count of approximately 2.46 × 10, nearly ten times the initial count. The use of Celcradle™ substantially decreased the time required for cell yield and virus production compared to conventional Petri dish methods. Moreover, our evaluation of the immunogenicity of the Celcradle™-produced inactivated DENV4 through immunization of mice revealed that sera from these mice demonstrated cross-reactivity with DENV4 cultured in Petri dishes and showed elevated antibody titers compared to those from mice immunized with virus from Petri dishes. These results indicate that the dengue virus cultivated using the Celcradle™ system exhibited enhanced immunogenicity relative to that produced in traditional methods. In conclusion, our study highlights the potential of the Celcradle™ bioreactor for large-scale production of inactivated dengue virus vaccines, offering significant promise for reducing the global impact of dengue virus infections and accelerating the development of effective vaccination strategies.
PubMed: 38932292
DOI: 10.3390/vaccines12060563 -
Viruses May 2024The complete lack of yellow fever virus (YFV) in Asia, and the lack of urban YFV transmission in South America, despite the abundance of the peridomestic mosquito vector...
The complete lack of yellow fever virus (YFV) in Asia, and the lack of urban YFV transmission in South America, despite the abundance of the peridomestic mosquito vector () is an enigma. An immunologically naïve population of over 2 billion resides in Asia, with most regions infested with the urban YF vector. One hypothesis for the lack of Asian YF, and absence of urban YF in the Americas for over 80 years, is that prior immunity to related flaviviruses like dengue (DENV) or Zika virus (ZIKV) modulates YFV infection and transmission dynamics. Here we utilized an interferon α/β receptor knock-out mouse model to determine the role of pre-existing dengue-2 (DENV-2) and Zika virus (ZIKV) immunity in YF virus infection, and to determine mechanisms of cross-protection. We utilized African and Brazilian YF strains and found that DENV-2 and ZIKV immunity significantly suppresses YFV viremia in mice, but may or may not protect relative to disease outcomes. Cross-protection appears to be mediated mainly by humoral immune responses. These studies underscore the importance of re-assessing the risks associated with YF outbreak while accounting for prior immunity from flaviviruses that are endemic.
Topics: Animals; Yellow Fever; Mice; Cross Protection; Disease Models, Animal; Yellow fever virus; Zika Virus; Mice, Knockout; Zika Virus Infection; Dengue Virus; Receptor, Interferon alpha-beta; Antibodies, Viral; Flavivirus; Aedes; Dengue; Female; Viremia; Mosquito Vectors; Flavivirus Infections; Mice, Inbred C57BL
PubMed: 38932129
DOI: 10.3390/v16060836 -
Microorganisms May 2024Dengue virus (DENV) poses a significant threat to global health, infecting approximately 390 million people annually. This virus comprises four serotypes capable of...
Dengue virus (DENV) poses a significant threat to global health, infecting approximately 390 million people annually. This virus comprises four serotypes capable of causing severe disease. Genetic analyses are crucial for understanding the epidemiology, evolution, and spread of DENV. Although previous studies have focused on the envelope protein-coding (E) gene, only a few primers can efficiently detect and amplify the viral genes from multiple endemic countries simultaneously. In this study, we designed degenerate primer pairs for each DENV serotype to amplify and sequence the entire E gene, using globally representative sequences for each serotype. These primers were validated using DENV isolates from various Asian countries and demonstrated broad-spectrum detection capabilities and high-quality sequences. The primers provide effective tools for genetic analysis in the regions affected by dengue, aiding strain identification and epidemiological studies during outbreaks.
PubMed: 38930474
DOI: 10.3390/microorganisms12061092 -
Evolution of STAT2 resistance to flavivirus NS5 occurred multiple times despite genetic constraints.Nature Communications Jun 2024Zika and dengue virus nonstructural protein 5 antagonism of STAT2, a critical interferon signaling transcription factor, to suppress the host interferon response is...
Zika and dengue virus nonstructural protein 5 antagonism of STAT2, a critical interferon signaling transcription factor, to suppress the host interferon response is required for viremia and pathogenesis in a vertebrate host. This affects viral species tropism, as mouse STAT2 resistance renders only immunocompromised or humanized STAT2 mice infectable. Here, we explore how STAT2 evolution impacts antagonism. By measuring the susceptibility of 38 diverse STAT2 proteins, we demonstrate that resistance arose numerous times in mammalian evolution. In four species, resistance requires distinct sets of multiple amino acid changes that often individually disrupt STAT2 signaling. This reflects an evolutionary ridge where progressive resistance is balanced by the need to maintain STAT2 function. Furthermore, resistance may come with a fitness cost, as resistance that arose early in lemur evolution was subsequently lost in some lemur lineages. These findings underscore that while it is possible to evolve resistance to antagonism, complex evolutionary trajectories are required to avoid detrimental host fitness consequences.
Topics: STAT2 Transcription Factor; Animals; Viral Nonstructural Proteins; Evolution, Molecular; Humans; Mice; Dengue Virus; Zika Virus; Flavivirus; Phylogeny; Host-Pathogen Interactions
PubMed: 38926343
DOI: 10.1038/s41467-024-49758-0 -
Reviews in Medical Virology Jul 2024Liver involvement is an unusual yet frequently overlooked dengue complication. Pivotal for an efficient clinical management, the early diagnosis of dengue-associated...
Liver involvement is an unusual yet frequently overlooked dengue complication. Pivotal for an efficient clinical management, the early diagnosis of dengue-associated liver involvement relies on an accurate description of its clinical and biological characteristics, its prognosis factors, its association with severe dengue and its clinical management. We conducted a systematic review by searching PubMed and Web of Science databases for original case reports, cohort and cross-sectional studies reporting the clinical and/or biological features of dengue-associated liver involvement. The study was registered in PROSPERO (CRD42021262657). Of the 2552 articles identified, 167 were included. Dengue-associated liver involvement was characterised by clinical features including abdominal pain, hepatomegaly, jaundice, nausea/vomiting, and an echogenic liver exhibiting hepatocellular necrosis and minimal inflammation. Elevated Aspartate Aminotransferase and Alanine Aminotransferase but also elevated bilirubin, Alkaline Phosphatase, gamma-glutamyl transferase, increased International Normalised Ratio, creatinine and creatine kinase, lower albumin and prolonged prothrombin and activated partial thromboplastin time were prevalent in dengue-associated liver involvement. Cardiovascular and haematological systems were frequently affected, translating in a strong association with severe dengue. Liver involvement was more common in males and older adults. It was associated with dengue virus serotype-2 and secondary infections. Early paracetamol intake increased the risk of liver involvement, which clinical management was mostly conservative. In conclusion, this systematic review demonstrates that early monitoring of transaminases, clinical assessment, and ultrasound examination allow an efficient diagnosis of dengue-associated liver involvement, enabling the early identification and management of severe dengue.
Topics: Humans; Dengue; Dengue Virus; Liver; Liver Diseases
PubMed: 38923215
DOI: 10.1002/rmv.2564 -
Journal of Vector Borne Diseases Apr 2024In Port Blair, the capital of Andaman & Nicobar Islands, in the Bay of Bengal, India, there was a sudden increase in fever cases resembling the symptoms of dengue in the...
BACKGROUND OBJECTIVES
In Port Blair, the capital of Andaman & Nicobar Islands, in the Bay of Bengal, India, there was a sudden increase in fever cases resembling the symptoms of dengue in the monsoon period of 2022. Hence, an investigation was carried out to find out epidemiological and entomological reasons behind the outbreak.
METHODS
An entomological survey was carried out in 24 wards of Port Blair Municipal Council (PBMC) area, epidemiological data of last six years (January-December 2017-2021 and January-October 2022) and patient details of the year 2022 were collected. Both the epidemiological and entomological data were analyzed concerning time and place.
RESULTS
During this outbreak period tyres (22.4%) came out as a major breeding habitat followed by small discarded materials (17.5%), metal drums (15.3%), and plastic drums (11.7%). In rainy season, peri-domestic breeding (55%) was more than the domestic breeding (45%) habitat. Ae. aegypti had a high preference for indoor large containers (100-1000 L) like plastic tank, metal drum and cement tank whereasAe. albopictus prefers to breed in medium sized plastic container (20-100 L) and outdoor water receptacles like tyres, flower pots, and domestic discarded materials.
INTERPRETATION CONCLUSION
By source reduction, indoor space spray and outdoor fogging, vector density was controlled which curtailed the transmission and within eight weeks a decreasing trend of dengue cases was noticed. A regular entomological survey is crucial to know the seasonality and key breeding habitats of the vector for proper planning of vector control.
Topics: India; Dengue; Animals; Humans; Disease Outbreaks; Aedes; Mosquito Vectors; Seasons; Ecosystem; Female; Male; Adult; Adolescent; Young Adult; Child; Middle Aged; Islands; Dengue Virus; Child, Preschool
PubMed: 38922656
DOI: 10.4103/jvbd.jvbd_144_23 -
In silico screening of potential plant peptides against the non-structural proteins of dengue virus.Journal of Vector Borne Diseases Apr 2024Peptides isolated from different sources of plants have the advantages of specificity, lower toxicity, and increased therapeutic effects; hence, it is necessary to...
BACKGROUND OBJECTIVES
Peptides isolated from different sources of plants have the advantages of specificity, lower toxicity, and increased therapeutic effects; hence, it is necessary to search for newer antivirals from plant sources for the treatment of dengue viral infections.
METHODS
In silico screening of selected plant peptides against the non-structural protein 1, NS3 protease domain (NS2B-NS3Pro) with the cofactor and ATPase/helicase domain (NS3 helicase domain/NS3hel) of dengue virus was performed. The physicochemical characteristics of the peptides were calculated using Protparam tools, and the allergenicity and toxicity profiles were assessed using allergenFP and ToxinPred, respectively.
RESULTS
Among the tested compounds, Ginkbilobin demonstrated higher binding energy against three tested nonstructural protein targets. Kalata B8 demonstrated maximum binding energy against NSP-1 and NSP-2, whereas Circulin A acted against the NSP3 protein of dengue virus.
INTERPRETATION CONCLUSION
The three compounds identified by in silico screening can be tested in vitro, which could act as potential leads as they are involved in hampering the replication of the dengue virus by interacting with the three prime non-structural proteins.
Topics: Viral Nonstructural Proteins; Dengue Virus; Antiviral Agents; Computer Simulation; Peptides; Plant Proteins; Molecular Docking Simulation; Serine Endopeptidases; RNA Helicases; Viral Proteases
PubMed: 38922655
DOI: 10.4103/jvbd.jvbd_47_23