-
Science Translational Medicine Oct 2023Emerging zoonotic mosquito-borne viruses pose increasing health threats because of growing mosquito population, geographic expansions, and control challenges. We... (Review)
Review
Emerging zoonotic mosquito-borne viruses pose increasing health threats because of growing mosquito population, geographic expansions, and control challenges. We emphasize the need for global preparedness to effectively mitigate the health, societal, and economic impacts of spillover by these viruses through proactive measures of prediction, surveillance, prevention, and treatment.
Topics: Animals; Arboviruses; Arbovirus Infections; Culicidae
PubMed: 37851824
DOI: 10.1126/scitranslmed.adj2166 -
Emerging Microbes & Infections Dec 2023Rift Valley fever (RVF) is an arboviral disease of zoonotic origin that causes recurrent epidemics in Africa, the Arabic Peninsula, and islands of the South West of the...
Rift Valley fever (RVF) is an arboviral disease of zoonotic origin that causes recurrent epidemics in Africa, the Arabic Peninsula, and islands of the South West of the Indian Ocean. RVF occurs mainly in livestock but also affects humans with severe clinical manifestations, including neurological disorders. However, human neuropathogenesis of Rift Valley fever virus (RVFV) is still poorly characterized. To study the interactions between RVFV and the central nervous system (CNS), we focused on RVFV infection of astrocytes, the major glial cells of the CNS that have several supporting roles including immune response regulation. We confirmed the permissiveness of astrocytes to RVFV infection and highlighted a strain-dependent infectivity. We showed that RVFV infection of astrocytes induced cell apoptosis and observed that the RVFV Non-Structural protein NSs, a known virulence factor, potentially delayed apoptosis by sequestrating activated-caspase 3 in the nucleus. Our study also showed that RVFV-infected astrocytes upregulated expression of genes associated with inflammatory and type I interferon responses at the mRNA level, but not at the protein level. This inhibition of immune response is potentially due to a NSs-dependent mechanism of mRNA nuclear export inhibition. Together, these results highlighted the direct impact of RVFV infection on the human CNS through the induction of apoptosis and a possible inhibition of early-onset immune responses that are crucial for the host survival.
Topics: Animals; Humans; Rift Valley fever virus; Astrocytes; Rift Valley Fever; Immunity; RNA, Messenger
PubMed: 37306630
DOI: 10.1080/22221751.2023.2207672 -
PLoS Neglected Tropical Diseases Aug 2023Severe dengue occurrence has been attributed to increasing age and different dengue virus (DENV) serotypes that cause secondary infections and immune-enhancing...
Severe dengue occurrence has been attributed to increasing age and different dengue virus (DENV) serotypes that cause secondary infections and immune-enhancing phenomena. Therefore, we examined if the effect of age on dengue severity was mediated by infectivity status while controlling for sex and region. Further, we assessed the spatial clustering of dengue severity for individuals with primary and secondary infection across Mexican municipalities. Health data from 2012 to 2017 was retrieved from Mexico's Ministry of Health. A mediation analysis was performed using multiple logistic regression models based on a directed acyclic graph. The models were explored for the direct effect of age on dengue severity and its indirect impact through secondary infection. In addition, severe dengue clusters were determined in some Northeastern and Southeastern municipalities through spatial analysis. We observed a nonlinear trend between age and severe dengue. There was a downward trend of severe dengue for individuals between 0 and 10 years and an upward trend above 10 years. The effect of age on dengue severity was no longer significant for individuals between 10 and 60 years after introducing infectivity status into the model. The mediating role of infectivity status in the causal model was 17%. Clustering of severe dengue among individuals with primary infection in the Northeastern region may point to the high prevalence of DENV-3 in the region. Public health efforts may prevent secondary infection among infants and the aged. In addition, there should be a further investigation into the effect of DENV-3 in individuals with primary disease.
Topics: Infant; Humans; Aged; Severe Dengue; Dengue; Dengue Virus; Coinfection; Serogroup; Antibodies, Viral
PubMed: 37556473
DOI: 10.1371/journal.pntd.0011537 -
The EMBO Journal May 2024Mosquitoes transmit many disease-relevant flaviviruses. Efficient viral transmission to mammalian hosts requires mosquito salivary factors. However, the specific...
Mosquitoes transmit many disease-relevant flaviviruses. Efficient viral transmission to mammalian hosts requires mosquito salivary factors. However, the specific salivary components facilitating viral transmission and their mechanisms of action remain largely unknown. Here, we show that a female mosquito salivary gland-specific protein, here named A. aegypti Neutrophil Recruitment Protein (AaNRP), facilitates the transmission of Zika and dengue viruses. AaNRP promotes a rapid influx of neutrophils, followed by virus-susceptible myeloid cells toward mosquito bite sites, which facilitates establishment of local infection and systemic dissemination. Mechanistically, AaNRP engages TLR1 and TLR4 of skin-resident macrophages and activates MyD88-dependent NF-κB signaling to induce the expression of neutrophil chemoattractants. Inhibition of MyD88-NF-κB signaling with the dietary phytochemical resveratrol reduces AaNRP-mediated enhancement of flavivirus transmission by mosquitoes. These findings exemplify how salivary components can aid viral transmission, and suggest a potential prophylactic target.
Topics: Animals; Aedes; Female; Zika Virus; Mice; Dengue Virus; Salivary Proteins and Peptides; Mosquito Vectors; Insect Proteins; Myeloid Cells; Zika Virus Infection; Dengue; NF-kappa B; Signal Transduction; Myeloid Differentiation Factor 88
PubMed: 38378891
DOI: 10.1038/s44318-024-00056-x -
Frontiers in Public Health 2023Dengue has been endemic in Southeast Asian countries for decades. There are few reports tracing the dynamics of dengue in real time. In this study, we generated hundreds...
OBJECTIVES
Dengue has been endemic in Southeast Asian countries for decades. There are few reports tracing the dynamics of dengue in real time. In this study, we generated hundreds of pathogen genomes to understand the genomic epidemiology of an outbreak in a hyper-endemic area of dengue.
METHODS
We leveraged whole-genome short-read sequencing (PE150) to generate genomes of the dengue virus and investigated the genomic epidemiology of a dengue virus transmission in a mesoscale outbreak in Shantou, China, in 2019.
RESULTS
The outbreak was sustained from July to December 2019. The total accumulated number of laboratory-confirmed cases was 944. No gender bias or fatalities were recorded. Cambodia and Singapore were the main sources of imported dengue cases (74.07%, = 20). A total of 284 dengue virus strains were isolated, including 259 DENV-1, 24 DENV-2, and 1 DENV-3 isolates. We generated the entire genome of 252 DENV isolates (229 DENV-1, 22 DENV-2, and 1 DENV-3), which represented 26.7% of the total cases. Combined epidemiological and phylogenetic analyses indicated multiple independent introductions. The internal transmission evaluations and transmission network reconstruction supported the inference of phylodynamic analysis, with high Bayes factor support in BSSVS analysis. Two expansion founders and transmission chains were detected in CCH and LG of Shantou.
CONCLUSIONS
We observed the instant effects of genomic epidemiology in monitoring the dynamics of DENV and highlighted its prospects for real-time tracing of outbreaks of other novel agents in the future.
Topics: China; Dengue; Humans; Genome, Viral; Dengue Virus; Disease Outbreaks; Phylogeny; Male; Female; Young Adult; Adult; Middle Aged; Infant; Child, Preschool; Child; Adolescent; Aged; Aged, 80 and over
PubMed: 37522010
DOI: 10.3389/fpubh.2023.1035060 -
Nature Microbiology Apr 2024Some viruses are rarely transmitted orally or sexually despite their presence in saliva, breast milk, or semen. We previously identified that extracellular vesicles...
Some viruses are rarely transmitted orally or sexually despite their presence in saliva, breast milk, or semen. We previously identified that extracellular vesicles (EVs) in semen and saliva inhibit Zika virus infection. However, the antiviral spectrum and underlying mechanism remained unclear. Here we applied lipidomics and flow cytometry to show that these EVs expose phosphatidylserine (PS). By blocking PS receptors, targeted by Zika virus in the process of apoptotic mimicry, they interfere with viral attachment and entry. Consequently, physiological concentrations of EVs applied in vitro efficiently inhibited infection by apoptotic mimicry dengue, West Nile, Chikungunya, Ebola and vesicular stomatitis viruses, but not severe acute respiratory syndrome coronavirus 2, human immunodeficiency virus 1, hepatitis C virus and herpesviruses that use other entry receptors. Our results identify the role of PS-rich EVs in body fluids in innate defence against infection via viral apoptotic mimicries, explaining why these viruses are primarily transmitted via PS-EV-deficient blood or blood-ingesting arthropods rather than direct human-to-human contact.
Topics: Female; Humans; Phosphatidylserines; Viruses; Extracellular Vesicles; Virus Attachment; Zika Virus; Body Fluids; Zika Virus Infection
PubMed: 38528146
DOI: 10.1038/s41564-024-01637-6 -
Viruses Sep 2023African swine fever (ASF) is a highly contagious and economically devastating disease affecting domestic pigs and wild boar, caused by African swine fever virus (ASFV).... (Review)
Review
African swine fever (ASF) is a highly contagious and economically devastating disease affecting domestic pigs and wild boar, caused by African swine fever virus (ASFV). Despite being harmless to humans, ASF poses significant challenges to the swine industry, due to sudden losses and trade restrictions. The ongoing COVID-19 pandemic has spurred an unparalleled global research effort, yielding remarkable advancements across scientific disciplines. In this review, we explore the potential technological spillover from COVID-19 research into ASF. Specifically, we assess the applicability of the diagnostic tools, vaccine development strategies, and biosecurity measures developed for COVID-19 for combating ASF. Additionally, we discuss the lessons learned from the pandemic in terms of surveillance systems and their implications for managing ASF. By bridging the gap between COVID-19 and ASF research, we highlight the potential for interdisciplinary collaboration and technological spillovers in the battle against ASF.
Topics: Animals; Humans; Swine; African Swine Fever; African Swine Fever Virus; COVID-19; Pandemics; Sus scrofa
PubMed: 37766331
DOI: 10.3390/v15091925 -
International Journal of Infectious... Feb 2024
Topics: Humans; Incidence; Climate Change; Dengue; Yellow Fever; Zika Virus Infection; Chikungunya Fever; Zika Virus
PubMed: 38096974
DOI: 10.1016/j.ijid.2023.12.004 -
Microbiology Spectrum Aug 2023Humans infected with dengue virus (DENV) acquire long-term protection against the infecting serotype, whereas cross-protection against other serotypes is short-lived....
Humans infected with dengue virus (DENV) acquire long-term protection against the infecting serotype, whereas cross-protection against other serotypes is short-lived. Long-term protection induced by low levels of type-specific neutralizing antibodies can be assessed using the virus-neutralizing antibody test. However, this test is laborious and time-consuming. In this study, a blockade-of-binding enzyme-linked immunoassay was developed to assess antibody activity by using a set of neutralizing anti-E monoclonal antibodies and blood samples from dengue virus-infected or -immunized macaques. Diluted blood samples were incubated with plate-bound dengue virus particles before the addition of an enzyme-conjugated antibody specific to the epitope of interest. Based on blocking reference curves constructed using autologous purified antibodies, sample blocking activity was determined as the relative concentration of unconjugated antibody that resulted in the same percent signal reduction. In separate DENV-1-, -2-, -3-, and -4-related sets of samples, moderate to strong correlations of the blocking activity with neutralizing antibody titers were found with the four type-specific antibodies 1F4, 3H5, 8A1, and 5H2, respectively. Significant correlations were observed for single samples taken 1 month after infection as well as samples drawn before and at various time points after infection/immunization. Similar testing using a cross-reactive EDE-1 antibody revealed a moderate correlation between the blocking activity and the neutralizing antibody titer only for the DENV-2-related set. The potential usefulness of the blockade-of-binding activity as a correlative marker of neutralizing antibodies against dengue viruses needs to be validated in humans. This study describes a blockade-of-binding assay for the determination of antibodies that recognize a selected set of serotype-specific or group-reactive epitopes in the envelope of dengue virus. By employing blood samples collected from dengue virus-infected or -immunized macaques, moderate to strong correlations of the epitope-blocking activities with the virus-neutralizing antibody titers were observed with serotype-specific blocking activities for each of the four dengue serotypes. This simple, rapid, and less laborious method should be useful for the evaluation of antibody responses to dengue virus infection and may serve as, or be a component of, an correlate of protection against dengue in the future.
Topics: Humans; Dengue Virus; Epitopes; Antibodies, Viral; Dengue; Antibodies, Neutralizing; Cross Reactions
PubMed: 37409936
DOI: 10.1128/spectrum.00918-23 -
Veterinary Research Jul 2023African swine fever (ASF), caused by ASF virus (ASFV) infection, poses a huge threat to the pork industry owing to ineffective preventive and control measures. Hence,...
African swine fever (ASF), caused by ASF virus (ASFV) infection, poses a huge threat to the pork industry owing to ineffective preventive and control measures. Hence, there is an urgent need to develop strategies, including antiviral drugs targeting ASFV, for preventing ASFV spread. This study aimed to identify novel compounds with anti-ASFV activity. To this end, we screened a small chemical library of 102 compounds, among which the natural flavonoid dihydromyricetin (DHM) exhibited the most potent anti-ASFV activity. DHM treatment inhibited ASFV replication in a dose- and time-dependent manner. Furthermore, it inhibited porcine reproductive and respiratory syndrome virus and swine influenza virus replication, which suggested that DHM exerts broad-spectrum antiviral effects. Mechanistically, DHM treatment inhibited ASFV replication in various ways in the time-to-addition assay, including pre-, co-, and post-treatment. Moreover, DHM treatment reduced the levels of ASFV-induced inflammatory mediators by regulating the TLR4/MyD88/MAPK/NF-κB signaling pathway. Meanwhile, DHM treatment reduced the ASFV-induced accumulation of reactive oxygen species, further minimizing pyroptosis by inhibiting the ASFV-induced NLRP3 inflammasome activation. Interestingly, the effects of DHM on ASFV were partly reversed by treatment with polyphyllin VI (a pyroptosis agonist) and RS 09 TFA (a TLR4 agonist), suggesting that DHM inhibits pyroptosis by regulating TLR4 signaling. Furthermore, targeting TLR4 with resatorvid (a specific inhibitor of TLR4) and small interfering RNA against TLR4 impaired ASFV replication. Taken together, these results reveal the anti-ASFV activity of DHM and the underlying mechanism of action, providing a potential compound for developing antiviral drugs targeting ASFV.
Topics: Animals; Swine; African Swine Fever Virus; Toll-Like Receptor 4; African Swine Fever; Pyroptosis; Antiviral Agents; Swine Diseases
PubMed: 37438783
DOI: 10.1186/s13567-023-01184-8