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Journal of Translational Medicine Jul 2023Viral therapies developed for cancer treatment have classically prioritized direct oncolytic effects over their immune activating properties. However, recent clinical...
BACKGROUND
Viral therapies developed for cancer treatment have classically prioritized direct oncolytic effects over their immune activating properties. However, recent clinical insights have challenged this longstanding prioritization and have shifted the focus to more immune-based mechanisms. Through the potential utilization of novel, inherently immune-stimulating, oncotropic viruses there is a therapeutic opportunity to improve anti-tumor outcomes through virus-mediated immune activation. PV001-DV is an attenuated strain of Dengue virus (DEN-1 #45AZ5) with a favorable clinical safety profile that also maintains the potent immune stimulatory properties characterstic of Dengue virus infection.
METHODS
In this study, we utilized in vitro tumor killing and immune multiplex assays to examine the anti-tumor effects of PV001-DV as a potential novel cancer immunotherapy.
RESULTS
In vitro assays demonstrated that PV001-DV possesses the ability to directly kill human melanoma cells lines as well as patient melanoma tissue ex vivo. Importantly, further work demonstrated that, when patient peripheral blood mononuclear cells (PBMCs) were exposed to PV001-DV, a substantial induction in the production of apoptotic factors and immunostimulatory cytokines was detected. When tumor cells were cultured with the resulting soluble mediators from these PBMCs, rapid cell death of melanoma and breast cancer cell lines was observed. These soluble mediators also increased dengue virus binding ligands and immune checkpoint receptor, PD-L1 expression.
CONCLUSIONS
The direct in vitro tumor-killing and immune-mediated tumor cytotoxicity facilitated by PV001-DV contributes support of its upcoming clinical evaluation in patients with advanced melanoma who have failed prior therapy.
Topics: Humans; Dengue Virus; Leukocytes, Mononuclear; Melanoma; MCF-7 Cells; Dengue; Immunity; Cell Death; Oncolytic Virotherapy; Oncolytic Viruses
PubMed: 37468934
DOI: 10.1186/s12967-023-04344-8 -
Le Infezioni in Medicina 2024Dengue is a vector-borne disease, especially important in tropical and subtropical areas. The first presentation of many arboviral diseases occurred mainly in animals,... (Review)
Review
INTRODUCTION
Dengue is a vector-borne disease, especially important in tropical and subtropical areas. The first presentation of many arboviral diseases occurred mainly in animals, including multiple and , such as dengue.
OBJECTIVE
To determine the serological and molecular frequency of the dengue virus in animals.
METHODS
A systematic literature review was carried out in five databases for the proportion of animals infected with dengue, defined by molecular and serological tests. A meta-analysis was performed using a random-effects model to calculate the pooled prevalence and 95% confidence intervals (CI). Cochran?s Q test and the I2 statistic were used to assess the heterogeneity between the two studies.
RESULTS
The presence of dengue in bats, primates, birds, sheep, horses, cattle, pigs, rodents and buffaloes, according to serological methods, had a prevalence of 10%, 29%, 8%, 1%, 11%, 0%, 49%, 2%, 7%, respectively. According to molecular methods, the presence of dengue in bats had a seroprevalence of 6.0%.
CONCLUSION
The present study confirms the presence of the Dengue virus in a large group of animal species, with potential implications as possible reservoirs of this virus, raising the possibility of zoonotic transmission.
PubMed: 38827825
DOI: 10.53854/liim-3202-7 -
Combinatorial Chemistry & High... Nov 2023Dengue, a mosquito-borne viral disease spread by the dengue virus (DENV), has become one of the most alarming health issues in the global scenario in recent days. The...
BACKGROUND
Dengue, a mosquito-borne viral disease spread by the dengue virus (DENV), has become one of the most alarming health issues in the global scenario in recent days. The risk of infection by DENV is mostly high in tropical and subtropical areas of the world. The mortality rate of patients affected with DENV is ever-increasing, mainly due to a lack of anti-dengue viral-specific synthetic drug components.
INTRODUCTION
Repurposing synthetic drugs has been an effective tool in combating several pathogens, including DENV. However, only the Dengvaxia vaccine has been developed so far to fight against the deadly disease despite the grave situation, mainly because of the limitations of understanding the actual pathogenicity of the disease.
METHODS
To address this particular issue and explore the actual disease pathobiology, several potential targets, like three structural proteins and seven non-structural (NS) proteins, along with their inhibitors of synthetic and natural origin, have been screened using docking simulation.
RESULTS
Exploration of these targets, along with their inhibitors, has been extensively studied in culmination with molecular docking-based screening to potentiate the treatment.
CONCLUSION
These screened inhibitors could possibly be helpful for the designing of new congeneric potential compounds to combat dengue fever and its complications.
PubMed: 37962048
DOI: 10.2174/0113862073247689231030153054 -
The American Journal of Tropical... Aug 2023Limited dengue virus (DENV) seroprevalence estimates are available for Puerto Rico, which are needed to inform the potential use and cost-effectiveness of DENV vaccines....
Limited dengue virus (DENV) seroprevalence estimates are available for Puerto Rico, which are needed to inform the potential use and cost-effectiveness of DENV vaccines. The Communities Organized to Prevent Arboviruses (COPA) is a cohort study initiated in 2018 in Ponce, Puerto Rico, to assess arboviral disease risk and provide a platform to evaluate interventions. We recruited participants from households in 38 study clusters, who were interviewed and provided a serum specimen. Specimens from 713 children aged 1 to 16 years during the first year of COPA were tested for the four DENV serotypes and ZIKV using a focus reduction neutralization assay. We assessed the seroprevalence of DENV and ZIKV by age and developed a catalytic model from seroprevalence and dengue surveillance data to estimate the force of infection for DENV during 2003-2018. Overall, 37% (n = 267) were seropositive for DENV; seroprevalence was 9% (11/128) among children aged 1 to 8 years and 44% (256/585) among children aged 9 to 16 years, exceeding the threshold over which DENV vaccination is deemed cost-effective. A total of 33% were seropositive for ZIKV, including 15% among children aged 0 to 8 years and 37% among children aged 9 to 16 years. The highest force of infection occurred in 2007, 2010, and 2012-2013, with low levels of transmission from 2016 to 2018. A higher proportion of children had evidence of multitypic DENV infection than expected, suggesting high heterogeneity in DENV risk in this setting.
Topics: Humans; Child; Dengue; Dengue Virus; Dengue Vaccines; Cohort Studies; Zika Virus Infection; Antibodies, Viral; Puerto Rico; Seroepidemiologic Studies; Zika Virus
PubMed: 37308104
DOI: 10.4269/ajtmh.23-0091 -
Archives of Virology Jul 2023Dengue is a viral disease transmitted by mosquitoes that has spread rapidly across all continents in recent years. There are four distinct but closely related serotypes... (Review)
Review
Dengue is a viral disease transmitted by mosquitoes that has spread rapidly across all continents in recent years. There are four distinct but closely related serotypes of the virus that causes dengue (DENV-1, DENV-2, DENV-3, and DENV-4). In the present study, we evaluated temporal spreading and molecular evolution of dengue virus (DENV) serotypes. Bayesian coalescent analysis was performed to study viral evolution, and it was estimated that the most recent common ancestor of DENV-1 was present in 1884 in Southeast Asia, that of DENV-2 was present in 1723 in Europe, that of DENV-3 was present in 1921 in Southeast Asia, and that of DENV-4 was present in 1876 in Southeast Asia. DENV appears to have originated in Spain in approximately 1682, and it was disseminated in Asia and Oceania in approximately 1847. After this period, the virus was introduced into North America in approximately 1890. In South America, it was first disseminated to Ecuador in approximately 1897 and then to Brazil in approximately 1910. Dengue has had a significant impact on global health worldwide, and the present study provides an overview of the molecular evolution of DENV serotypes.
Topics: Animals; Humans; Bayes Theorem; Brazil; Dengue; Dengue Virus; Evolution, Molecular; Phylogeny
PubMed: 37410187
DOI: 10.1007/s00705-023-05833-3 -
Emerging Infectious Diseases Feb 2024During May 2022-April 2023, dengue virus serotype 3 was identified among 601 travel-associated and 61 locally acquired dengue cases in Florida, USA. All 203 sequenced...
During May 2022-April 2023, dengue virus serotype 3 was identified among 601 travel-associated and 61 locally acquired dengue cases in Florida, USA. All 203 sequenced genomes belonged to the same genotype III lineage and revealed potential transmission chains in which most locally acquired cases occurred shortly after introduction, with little sustained transmission.
Topics: Humans; Dengue Virus; Dengue; Florida; Travel; Base Sequence; Genotype; Serogroup; Phylogeny
PubMed: 38232709
DOI: 10.3201/eid3002.231615 -
Computational and Structural... 2023Dengue fever (DF) and dengue hemorrhagic fever (DHF) are among the most common tropical diseases affecting humans. To analyze the risk of clinical and transmission of...
UNLABELLED
Dengue fever (DF) and dengue hemorrhagic fever (DHF) are among the most common tropical diseases affecting humans. To analyze the risk of clinical and transmission of DF/DHF in Shenzhen, the surveillance on patients of all-age patients with dengue virus (DENV) infections was conducted. Our findings revealed that the majority of DENV-infected patients are young to middle-aged males, and the development of the disease is accompanied by abnormal changes in the percentages of neutrophils, lymphocytes, and basophils. Demographic analysis revealed that these patients is concentrated in areas such as Futian District, which may be due to the higher mosquito density and temperature than that in other area. Subsequent, mosquito infection experiments confirmed that the effect of temperature shift on DENV proliferation and transmission. Not only that, constant temperatures can enhance the spread of DENV, even increase the risk of epidemic. Thus, the role of innate immune response should be highlighted in the prediction of severe severity of DENV-infected patients, and temperature should be taken into account in the prevention and control of DENV.
INTRODUCTION
Dengue fever (DF) and dengue hemorrhagic fever (DHF) are among the most common tropical diseases affecting humans, and which caused by the four dengue virus serotypes (DENV 1-4).
OBJECTIVES
To analyze the risk of clinical and transmission of DF/DHF in Shenzhen.
METHODS
The surveillance on patients of all-age patients with dengue virus (DENV) infections was conducted.
RESULTS
Our findings revealed that the majority of DENV-infected patients are young to middle-aged males, and the development of the disease is accompanied by abnormal changes in the percentages of neutrophils, lymphocytes, and basophils. Demographic analysis revealed that these patients is concentrated in areas such as Futian District, which may be due to the higher mosquito density and temperature than that in other area. Subsequent, mosquito infection experiments confirmed that the effect of temperature shift on DENV proliferation and transmission. Not only that, constant temperatures can enhance the spread of DENV, even increase the risk of epidemic.
CONCLUSION
1. Elevated levels of neutrophils, lymphocytes, basophils, and temperature are all significant risk factors for dengue transmission and pathogenesis; 2. Temperature increasing is associated with a higher risk of dengue transmission; 3. Fluctuations in temperature around 28 °C (28 ± 5 °C) would increase dengue transmission.
PubMed: 37560123
DOI: 10.1016/j.csbj.2023.07.001 -
Journal of Infection and Public Health Dec 2023Multiplex real-time PCR is a quick and cost effective method for detection of various gene simultaneously. HFSV (Hemorrhagic Fever Syndrome Virus) is a newly emerging...
BACKGROUND
Multiplex real-time PCR is a quick and cost effective method for detection of various gene simultaneously. HFSV (Hemorrhagic Fever Syndrome Virus) is a newly emerging infectious disease because of globalization and climate change. We tried to develop a molecular diagnostic technique for various causative viruses and evaluate its usefulness for improving public health.
METHODS
Molecular diagnostic test method that qualitatively detects viruses causing viral hemorrhagic fevers hired Taq-Man Real-time RT-PCR technique. The Ct value was experimentally observed three or more times at the RNA concentration before and after the detection limit. After designing a multiplex real-time RT-PCR test for target gene of selected 17 viruses, the detection limit for each target and the presence or absence of cross-reaction and interference reaction were evaluated to determine its availability.
RESULTS
Six kinds of viruses, including Crimean-Congo hemorrhagic fever virus, Omsk hemorrhagic fever virus, Sabia virus, Chapare virus, Yellow fever virus, and Variola virus (A4L gene, B12R gene), were able to confirm the detection limit of 0.5 copies/μl, and other Ebola virus, Marburg virus, Rift Valley fever virus, Kyasanur Forest disease virus, Junin virus, Guanarito virus, Machupo virus, Chikungunya virus, Hantavirus, Dengue virus types 1-4, and Lassa virus (L gene, GPC gene), and 11 kinds of viruses, the detection limit was confirmed at 5 copies/μl. No cross-reaction or interference between detected genes was observed.
CONCLUSION
The virus test method developed through this study using multiplex is expected to be used for public health and quarantine as a test method that can be used when a hemorrhagic fever virus of unknown cause is introduced.
Topics: Animals; Humans; Hemorrhagic Fever Virus, Crimean-Congo; Dengue Virus; Viruses; Arenaviruses, New World; Orthohantavirus; Polymerase Chain Reaction
PubMed: 37866271
DOI: 10.1016/j.jiph.2023.10.012 -
Journal of Virology Nov 2023Currently licensed dengue vaccines do not induce long-term protection in children without previous exposure to dengue viruses in nature. These vaccines are based on...
Currently licensed dengue vaccines do not induce long-term protection in children without previous exposure to dengue viruses in nature. These vaccines are based on selected attenuated strains of the four dengue serotypes and employed in combination for two or three consecutive doses. In our search for a better dengue vaccine candidate, live attenuated strains were followed by non-infectious virus-like particles or the plasmids that generate these particles upon injection into the body. This heterologous prime-boost immunization induced elevated levels of virus-specific antibodies and helped to prevent dengue virus infection in a high proportion of vaccinated macaques. In macaques that remained susceptible to dengue virus, distinct mechanisms were found to account for the immunization failures, providing a better understanding of vaccine actions. Additional studies in humans in the future may help to establish whether this combination approach represents a more effective means of preventing dengue by vaccination.
Topics: Animals; Humans; Antibodies, Viral; Dengue; Dengue Vaccines; Dengue Virus; Macaca fascicularis; Immunization, Secondary; Vaccines, Virus-Like Particle
PubMed: 37846984
DOI: 10.1128/jvi.00963-23 -
Nature Immunology Dec 2023
Topics: Humans; Severe Dengue; Dengue; Dengue Virus; Antibody-Dependent Enhancement; Antibodies, Viral
PubMed: 38012410
DOI: 10.1038/s41590-023-01680-1