Daily life affective dynamics as transdiagnostic predictors of mental health symptoms:An ecological momentary assessment study

BackgroundAffective dynamics have been identified as a correlate of a broad span of mental health issues, making them key candidate transdiagnostic factors. However, there remains a lack of knowledge about which aspects of affective dynamics – especially as they manifest in the course of daily life – relate to a general risk for mental health issues versus specific symptoms. MethodsWe leverage an ecological momentary assessment (EMA) study design with four measures per day over a two-week period to explore how negative affect levels, inertia, lability, and reactivity to provocation and stress in the course of daily life relate to mental health symptoms in young adults (n= 256) in the domains of anxiety, depression, psychosis-like symptoms, behaviour problems, suicidality, and substance use. ResultsDynamic structural equation modelling (DSEM) suggested that negative affect levels in daily life were associated with depression, anxiety, indirect and proactive aggression, psychosis, anxiety, and self-injury; negative affective lability was associated with depression, physical aggression, reactive aggression, suicidal ideation, and ADHD symptoms; negative affective inertia was associated with depression, anxiety, physical aggression, and cannabis use; and emotional reactivity to provocation was related to physical aggression. LimitationsThe cross-sectional design, the limited span of mental health issues included, and the convenience nature and small size of the sample are limitations.ConclusionsFindings suggest that a subset of mental health symptoms have shared negative affective dynamics patterns. Longitudinal research is needed to rigorously examine the directionality of the effects underlying the association between affective dynamics and mental health issues

Midgut transcriptomic responses to dengue and chikungunya viruses in the vectors Aedes albopictus and Aedes malayensis

Dengue (DENV) and chikungunya (CHIKV) viruses are among the most preponderant arboviruses. Although primarily transmitted through the bite of Aedes aegypti mosquitoes, Aedes albopictus and Aedes malayensis are competent vectors and have an impact on arbovirus epidemiology. Here, to fill the gap in our understanding of the molecular interactions between secondary vectors and arboviruses, we used transcriptomics to profile the whole-genome responses of A. albopictus to CHIKV and of A. malayensis to CHIKV and DENV at 1 and 4 days post-infection (dpi) in midguts. In A. albopictus, 1793 and 339 genes were significantly regulated by CHIKV at 1 and 4 dpi, respectively. In A. malayensis, 943 and 222 genes upon CHIKV infection, and 74 and 69 genes upon DENV infection were significantly regulated at 1 and 4 dpi, respectively. We reported 81 genes that were consistently differentially regulated in all the CHIKV-infected conditions, identifying a CHIKV-induced signature. We identified expressed immune genes in both mosquito species, using a de novo assembled midgut transcriptome for A. malayensis, and described the immune architectures. We found the JNK pathway activated in all conditions, generalizing its antiviral function to Aedines. Our comprehensive study provides insight into arbovirus transmission by multiple Aedes vectors

Peridomestic Aedes malayensis and Aedes albopictus are capable vectors of arboviruses in cities

International audienceBackground: Dengue and chikungunya are global re-emerging mosquito-borne diseases. In Singapore, sustained vector control coupled with household improvements reduced domestic mosquito populations for the past 45 years, particularly the primary vector Aedes aegypti. However, while disease incidence was low for the first 30 years following vector control implementation, outbreaks have re-emerged in the past 15 years. Epidemiological observations point to the importance of peridomestic infection in areas not targeted by control programs. We investigated the role of vectors in peri-domestic areas.Methods: We carried out entomological surveys to identify the Aedes species present in vegetated sites in highly populated areas and determine whether mosquitoes were present in open-air areas frequented by people. We compared vector competence of Aedes albopictus and Aedes malayensis with Ae. aegypti after oral infection with sympatric dengue serotype 2 and chikungunya viruses. Mosquito saliva was tested for the presence of infectious virus particles as a surrogate for transmission following oral infection.Results: We identified Aedes albopictus and Aedes malayensis throughout Singapore and quantified their presence in forested and opened grassy areas. Both Ae. albopictus and Ae. malayensis can occupy sylvatic niches and were highly susceptible to both arboviruses. A majority of saliva of infected Ae. malayensis contained infectious particles for both viruses.Conclusions:Our study reveals the prevalence of competent vectors in peri-domestic areas, including Ae. malayensis for which we established the vector status. Epidemics can be driven by infection foci, which are epidemiologically enhanced in the context of low herd immunity, selective pressure on arbovirus transmission and the presence of infectious asymptomatic persons, all these conditions being present in Singapore. Learning from Singapore’s vector control success that reduced domestic vector populations, but has not sustainably reduced arboviral incidence, we suggest including peri-domestic vectors in the scope of vector management

A Zika virus from America is more efficiently transmitted than an Asian virus by Aedes aegypti mosquitoes from Asia

International audienceZika is a mosquito-borne disease associated with neurological disorders that causes an ongoing pandemic. The first outbreak was recorded in Micronesia in 2007, then in French Polynesia in 2014 from which it spread to South America in 2015 and ignited a widespread epidemic. Interestingly, Zika outbreaks in Asia remained of moderate intensity although the virus is circulating. To understand these epidemiological variations, we investigated the entomological determinants of ZIKV transmission in Asia. We used oral infection of mosquitoes collected in Singapore to identify the vector species, to quantify the blood infection threshold and to compare transmissibility between an Asian ZIKV strain (H/PF13) and an American strain collected in Brazil (BE H 815744). We have confirmed the vector status of Aedes aegypti and determined that 10 3 pfu/ml of blood is sufficient to infect mosquitoes. We showed that only the American strain was present in the saliva 3 days post-infection, and that this strain had a 30-40% higher rate of saliva infection in Ae. aegypti from 3 to 14 days post-infection than the Asian strain. Our data suggests that American strains are more efficiently transmitted than Asian strains, which raises concerns about the introduction of American strains in Asia

Daily life affective dynamics as transdiagnostic predictors of mental health symptoms : An ecological momentary assessment study

Affective dynamics have been identified as a correlate of a broad span of mental health issues, making them key candidate transdiagnostic factors. However, there remains a lack of knowledge about which aspects of affective dynamics - especially as they manifest in the course of daily life - relate to a general risk for mental health issues versus specific symptoms. We leverage an ecological momentary assessment (EMA) study design with four measures per day over a two-week period to explore how negative affect levels, inertia, lability, and reactivity to provocation and stress in the course of daily life relate to mental health symptoms in young adults (n = 256) in the domains of anxiety, depression, psychosis-like symptoms, behaviour problems, suicidality, and substance use. Dynamic structural equation modelling (DSEM) suggested that negative affect levels in daily life were associated with depression, anxiety, indirect and proactive aggression, psychosis, anxiety, and self-injury; negative affective lability was associated with depression, physical aggression, reactive aggression, suicidal ideation, and ADHD symptoms; negative affective inertia was associated with depression, anxiety, physical aggression, and cannabis use; and emotional reactivity to provocation was related to physical aggression. The cross-sectional design, the limited span of mental health issues included, and the convenience nature and small size of the sample are limitations. Findings suggest that a subset of mental health symptoms have shared negative affective dynamics patterns. Longitudinal research is needed to rigorously examine the directionality of the effects underlying the association between affective dynamics and mental health issues

Dengue subgenomic flaviviral RNA disrupts immunity in mosquito salivary glands to increase virus transmission

International audienceGlobally re-emerging dengue viruses are transmitted from human-to-human by Aedes mosquitoes. While viral determinants of human pathogenicity have been defined, there is a lack of knowledge of how dengue viruses influence mosquito transmission. Identification of viral determinants of transmission can help identify isolates with high epidemiological potential. Additionally, mechanistic understanding of transmission will lead to better understanding of how dengue viruses harness evolution to cycle between the two hosts. Here, we identified viral determinants of transmission and characterized mechanisms that enhance production of infectious saliva by inhibiting immunity specifically in salivary glands. Combining oral infection of Aedes aegypti mosquitoes and reverse genetics, we identified two 3' UTR substitutions in epidemic isolates that increased subgenomic flaviviral RNA (sfRNA) quantity, infectious particles in salivary glands and infection rate of saliva, which represents a measure of transmission. We also demonstrated that various 3'UTR modifications similarly affect sfRNA quantity in both whole mosquitoes and human cells, suggesting a shared determinism of sfRNA quantity. Furthermore, higher relative quantity of sfRNA in salivary glands compared to midgut and carcass pointed to sfRNA function in salivary glands. We showed that the Toll innate immune response was preferentially inhibited in salivary glands by viruses with the 3'UTR substitutions associated to high epidemiological fitness and high sfRNA quantity, pointing to a mechanism for higher saliva infection rate. By determining that sfRNA is an immune suppressor in a tissue relevant to mosquito transmission, we propose that 3'UTR/sfRNA sequence evolution shapes dengue epidemiology not only by influencing human pathogenicity but also by increasing mosquito transmission, thereby revealing a viral determinant of epidemiological fitness that is shared between the two hosts. PLOS Pathogens | https://doi.org/10.1371/journal.ppat

Characterization of dengue virus 3’UTR RNA binding proteins in mosquitoes reveals that AeStaufen reduces subgenomic flaviviral RNA in saliva

International audienceDengue viruses (DENV) are expanding global pathogens that are transmitted through the bite of mosquitoes, mostly Aedes aegypti . As RNA viruses, DENV rely on RNA-binding proteins (RBPs) to complete their life cycle. Alternatively, RBPs can act as restriction factors that prevent DENV multiplication. While the importance of RBPs is well-supported in humans, there is a dearth of information about their influence on DENV transmission by mosquitoes. Such knowledge could be harnessed to design novel, effective interventions against DENV. Here, we successfully adapted RNA-affinity chromatography coupled with mass spectrometry–a technique initially developed in mammalian cells–to identify RBPs in Ae . aegypti cells. We identified fourteen RBPs interacting with DENV serotype 2 3’UTR, which is involved in the viral multiplication and produces subgenomic flaviviral RNA (sfRNA). We validated the RNA affinity results for two RBPs by confirming that AePur binds the 3’UTR, whereas AeStaufen interacts with both 3’UTR and sfRNA. Using in vivo functional evaluation, we determined that RBPs like AeRan, AeExoRNase, and AeRNase have pro-viral functions, whereas AeGTPase, AeAtu, and AePur have anti-viral functions in mosquitoes. Furthermore, we showed that human and mosquito Pur homologs have a shared affinity to DENV2 RNA, although the anti-viral effect is specific to the mosquito protein. Importantly, we revealed that AeStaufen mediates a reduction of gRNA and sfRNA copies in several mosquito tissues, including the salivary glands and that AeStaufen-mediated sfRNA reduction diminishes the concentration of transmission-enhancing sfRNA in saliva, thereby revealing AeStaufen’s role in DENV transmission. By characterizing the first RBPs that associate with DENV2 3’UTR in mosquitoes, our study unravels new pro- and anti-viral targets for the design of novel therapeutic interventions as well as provides foundation for studying the role of RBPs in virus-vector interactions

Infection rate and viral genome copies per infected <i>Ae</i>. <i>malayensis</i> 14 days after injection of saliva collected from DENV- or CHIKV-infected <i>Ae</i>. <i>malayensis</i>.

<p>nd; not detected.</p

Distribution of cases identified within and outside case-clusters from 1990 to 2014.

<p>A case-cluster is defined as two or more infected persons epidemiologically linked by place [within 150m (200m till 2002)] with respect to their home address and time (within 14 days). Numbers above bars represent percentage of cases outside clusters [<a href="http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0005667#pntd.0005667.ref030" target="_blank">30</a>].</p

Infection and dissemination abilities for DENV and CHIKV in <i>Ae</i>. <i>aegypti</i>, <i>Ae</i>. <i>albopictus</i> and <i>Ae</i>. <i>malayensis</i>.

<p>Mosquitoes were orally infected with the virus and analyzed after 14 days. (A) Infection and dissemination rates for DENV. (B) DENV genome copies per infected tissue in abdomen and thorax. (C) Infection and dissemination rates for CHIKV. (D) CHIKV genome copies per infected tissue in abdomen and thorax. (A and C) Each point represents an independent repeat of 25 mosquitoes. Bars show mean ± s.e.m. T-test significant differences between mosquito species are shown. (B and D). Table below indicates the results from a two-ANOVA testing the impact of species and tissues on viral genome copies per infected tissues.</p