The global emergence of Zika revealed the unprecedented ability of a mosquito-borne virus to cause severe congenital abnormalities. Recent studies indicate that the ability to harm fetuses is not a ...novel feature of Zika virus. Counter-intuitively, it may have in fact recently ‘attenuated’ from killing embryos to causing birth defects.
By defining Σα as the sum of all additive effects and Σβ as the sum of all interaction effects (both within and between loci), the previous equation can be generalized to any trait determined ...by multiple (n>2) loci: (Equation 2.2) By incorporating this expression into the general quantitative genetic model given by equation 1.1, we obtain the expression: (Equation 1.3) Likewise, using the quantitative genetic model of host-pathogen interactions given by equation 1.2, it follows: (Equation 1.4) By using the notations ΣαHP = ΣαH+ΣαP (sum of additive effects of host and pathogen loci) and ΣβHP = ΣβH+ΣβP+gHP (sum of interaction effects between host loci, between pathogen loci, and specific GxG interactions between host and pathogen loci), the equation becomes: (Equation 1.5) The striking similarity between equations 1.5 and 1.3 illustrates how the phenotype of a host-pathogen interaction can simply be modeled as that of a third organism that combines both genomes. A major caveat of these QTL mapping and association studies is that they focus on either the host or the pathogen genome. Because they consider variation in only one of the two interacting organisms, these studies ignore specific host genome by pathogen genome interactions.
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Similar to many other host–pathogen interactions, the vector competence of Aedes aegypti for dengue viruses appears to be determined by genotype-by-genotype interactions, whereby the outcome of ...infection depends on the specific combination of mosquito and virus genotypes. This can complicate efforts to dissect the genetic basis of vector competence in nature because it obscures mapping between genotype and phenotype and brings into question the notion of universal mosquito resistance or susceptibility. Conversely, it offers novel opportunities to better define compatible vector–pathogen associations based on integration of both vector and pathogen genomics, which should eventually improve understanding of pathogen transmission dynamics and the risk of vector-borne disease emergence.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
The dramatic global expansion of Aedes albopictus in the last three decades has increased public health concern because it is a potential vector of numerous arthropod-borne viruses (arboviruses), ...including the most prevalent arboviral pathogen of humans, dengue virus (DENV). Ae. aegypti is considered the primary DENV vector and has repeatedly been incriminated as a driving force in dengue's worldwide emergence. What remains unresolved is the extent to which Ae. albopictus contributes to DENV transmission and whether an improved understanding of its vector status would enhance dengue surveillance and prevention. To assess the relative public health importance of Ae. albopictus for dengue, we carried out two complementary analyses. We reviewed its role in past dengue epidemics and compared its DENV vector competence with that of Ae. aegypti. Observations from "natural experiments" indicate that, despite seemingly favorable conditions, places where Ae. albopictus predominates over Ae. aegypti have never experienced a typical explosive dengue epidemic with severe cases of the disease. Results from a meta-analysis of experimental laboratory studies reveal that although Ae. albopictus is overall more susceptible to DENV midgut infection, rates of virus dissemination from the midgut to other tissues are significantly lower in Ae. albopictus than in Ae. aegypti. For both indices of vector competence, a few generations of mosquito colonization appear to result in a relative increase of Ae. albopictus susceptibility, which may have been a confounding factor in the literature. Our results lead to the conclusion that Ae. albopictus plays a relatively minor role compared to Ae. aegypti in DENV transmission, at least in part due to differences in host preferences and reduced vector competence. Recent examples of rapid arboviral adaptation to alternative mosquito vectors, however, call for cautious extrapolation of our conclusion. Vector status is a dynamic process that in the future could change in epidemiologically important ways.
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Mosquitoes develop long-lasting viral infections without substantial deleterious effects, despite high viral loads. This makes mosquitoes efficient vectors for emerging viral diseases with enormous ...burden on public health. How mosquitoes resist and/or tolerate these viruses is poorly understood. Here we show that two species of Aedes mosquitoes infected with two arboviruses from distinct families (dengue or chikungunya) generate a viral-derived DNA (vDNA) that is essential for mosquito survival and viral tolerance. Inhibition of vDNA formation leads to extreme susceptibility to viral infections, reduction of viral small RNAs due to an impaired immune response, and loss of viral tolerance. Our results highlight an essential role of vDNA in viral tolerance that allows mosquito survival and thus may be important for arbovirus dissemination and transmission. Elucidating the mechanisms of mosquito tolerance to arbovirus infection paves the way to conceptualize new antivectorial strategies to selectively eliminate arbovirus-infected mosquitoes.
Vertical transmission (VT) and horizontal transmission (HT) of pathogens refer to parental and non-parental chains of host-to-host transmission. Combining HT with VT enlarges considerably the range ...of ecological conditions in which a pathogen can persist, but the factors governing the relative frequency of each transmission mode are poorly understood for pathogens with mixed-mode transmission. Elucidating these factors is particularly important for understanding the epidemiology of arthropod-borne viruses (arboviruses) of public health significance. Arboviruses are primarily maintained by HT between arthropod vectors and vertebrate hosts in nature, but are occasionally transmitted vertically in the vector population from an infected female to her offspring, which is a proposed maintenance mechanism during adverse conditions for HT. Here, we review over a century of published primary literature on natural and experimental VT, which we previously assembled into large databases, to identify biological factors associated with the efficiency of arbovirus VT in mosquito vectors. Using a robust statistical framework, we highlight a suite of environmental, taxonomic, and physiological predictors of arbovirus VT. These novel insights contribute to refine our understanding of strategies employed by arboviruses to persist in the environment and cause substantial public health concern. They also provide hypotheses on the biological processes underlying the relative VT frequency for pathogens with mixed-mode transmission that can be tested empirically.
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•The extent and epidemiological importance of arbovirus VT are still debated.•Arboviral emergence events have stimulated VT research.•More recent laboratory assays are associated with enhanced VT ...detection.•Typically <0.1% of mosquitoes are vertically infected in nature.•The outcome of VT studies is context- and method-dependent.
Arthropod-borne viruses (arboviruses) are mainly transmitted horizontally among vertebrate hosts by blood-feeding invertebrate vectors, but can also be transmitted vertically in the vector from an infected female to its offspring. Vertical transmission (VT) is considered a possible mechanism for the persistence of arboviruses during periods unfavorable for horizontal transmission, but the extent and epidemiological significance of this phenomenon have remained controversial. To help resolve this question, we reviewed over a century of published literature on VT to analyze historical trends of scientific investigations on experimental and natural occurrence of VT in mosquitoes. Our synthesis highlights the influence of major events of public health significance in arbovirology on the number of VT publications. Epidemiological landmarks such as emergence events have significantly stimulated VT research. Our analysis also reveals the association between the evolution of virological assays and the probability of VT detection. Increased sensitivity and higher-throughput of modern laboratory assays resulted in enhanced VT detection. In general, VT contribution to arbovirus persistence is likely modest because vertically infected mosquitoes are rarely observed in nature. Taken together, however, our results call for caution when interpreting VT studies because their conclusions are context- and method-dependent.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Interactions between pathogens and their insect vectors in nature are under the control of both genetic and non-genetic factors, yet most studies on mosquito vector competence for human pathogens are ...conducted in laboratory systems that do not consider genetic and/or environmental variability. Evaluating the risk of emergence of arthropod-borne viruses (arboviruses) of public health importance such as chikungunya virus (CHIKV) requires a more realistic appraisal of genetic and environmental contributions to vector competence. In particular, sources of variation do not necessarily act independently and may combine in the form of interactions. Here, we measured CHIKV transmission potential by the mosquito Aedes albopictus in all combinations of six worldwide vector populations, two virus strains and two ambient temperatures (20°C and 28°C). Overall, CHIKV transmission potential by Ae. albopictus strongly depended on the three-way combination of mosquito population, virus strain and temperature. Such genotype-by-genotype-by-environment (G × G × E) interactions question the relevance of vector competence studies conducted with a simpler set of conditions. Our results highlight the need to account for the complex interplay between vectors, pathogens and environmental factors to accurately assess the potential of vector-borne diseases to emerge.
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The effect of temperature on insect biology is well understood under constant temperature conditions, but less so under more natural, fluctuating conditions. A fluctuating temperature profile around ...a mean of 26°C can alter Aedes aegypti vector competence for dengue viruses as well as numerous life-history traits, however, the effect of fluctuations on mosquitoes at critical thermal limits is unknown.
We investigated the effects of large and small daily temperature fluctuations at low (16°C) and high (35-37°C) mean temperatures, after we identified these temperatures as being thresholds for immature development and/or adult reproduction under constant temperature conditions. We found that temperature effects on larval development time, larval survival and adult reproduction depend on the combination of mean temperature and magnitude of fluctuations. Importantly, observed degree-day estimates for mosquito development under fluctuating temperature profiles depart significantly (around 10-20%) from that predicted by constant temperatures of the same mean. At low mean temperatures, fluctuations reduce the thermal energy required to reach pupation relative to constant temperature, whereas at high mean temperatures additional thermal energy is required to complete development. A stage-structured model based on these empirical data predicts that fluctuations can significantly affect the intrinsic growth rate of mosquito populations.
Our results indicate that by using constant temperatures, one could under- or over-estimate values for numerous life-history traits compared to more natural field conditions dependent upon the mean temperature. This complexity may in turn reduce the accuracy of population dynamics modeling and downstream applications for mosquito surveillance and disease prevention.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Three-quarters of the estimated 390 million dengue virus (DENV) infections each year are clinically inapparent. People with inapparent dengue virus infections are generally considered dead-end hosts ...for transmission because they do not reach sufficiently high viremia levels to infect mosquitoes. Here, we show that, despite their lower average level of viremia, asymptomatic people can be infectious to mosquitoes. Moreover, at a given level of viremia, DENV-infected people with no detectable symptoms or before the onset of symptoms are significantly more infectious to mosquitoes than people with symptomatic infections. Because DENV viremic people without clinical symptoms may be exposed to more mosquitoes through their undisrupted daily routines than sick people and represent the bulk of DENV infections, our data indicate that they have the potential to contribute significantlymore to virus transmission to mosquitoes than previously recognized.
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