Can Vaccination Save a Zika Virus Epidemic?

Zika virus (ZIKV) is a vector-borne disease that has rapidly spread during the year 2016 in more than 50 countries around the world. If a woman is infected during pregnancy, the virus can cause severe birth defects and brain damage in their babies. The virus can be transmitted through the bites of infected mosquitoes as well as through direct contact from human to human (e.g., sexual contact and blood transfusions). As an intervention for controlling the spread of the disease, we study a vaccination model for preventing Zika infections. Although there is no formal vaccine for ZIKV, The National Institute of Allergy and Infectious Diseases (part of the National Institutes of Health) has launched a vaccine trial at the beginning of August 2016 to control ZIKV transmission, patients who received the vaccine are expected to return within 44 weeks to determine if the vaccine is safe. Since it is important to understand ZIKV dynamics under vaccination, we formulate a vaccination model for ZIKV spread that includes mosquito as well as sexual transmission. We calculate the basic reproduction number of the model to analyze the impact of relatively, perfect and imperfect vaccination rates. We illustrate several numerical examples of the vaccination model proposed as well as the impact of the basic reproduction numbers of vector and sexual transmission and the effect of vaccination effort on ZIKV spread. Results show that high levels of sexual transmission create larger cases of infection associated with the peak of infected humans arising in a shorter period of time, even when a vaccine is available in the population. However, a high level of transmission of Zika from vectors to humans compared with sexual transmission represents that ZIKV will take longer to invade the population providing a window of opportunities to control its spread, for instance, through vaccination.     

Zika Virus,a New Threat for Europe?

BackgroundSince its emergence in 2007 in Micronesia and Polynesia, the arthropod-borne flavivirus Zika virus (ZIKV) has spread in the Americas and the Caribbean, following first detection in Brazil in May 2015. The risk of ZIKV emergence in Europe increases as imported cases are repeatedly reported. Together with chikungunya virus (CHIKV) and dengue virus (DENV), ZIKV is transmitted by Aedes mosquitoes. Any countries where these mosquitoes are present could be potential sites for future ZIKV outbreak. We assessed the vector competence of European Aedes mosquitoes (Aedes aegypti and Aedes albopictus) for the currently circulating Asian genotype of ZIKV.Conclusions/SignificanceIn combination with the restricted distribution of European Ae. albopictus, our results on vector competence corroborate the low risk for ZIKV to expand into most parts of Europe with the possible exception of the warmest regions bordering the Mediterranean coastline.     

Did the Food Environment Cause the Obesity Epidemic?

Several putative explanations of the obesity epidemic relate to the changing food environment. Individual dietary macronutrients have each been theorized to be the prime culprit for population obesity, but these explanations are unlikely. Rather, obesity probably resulted from changes in the caloric quantity and quality of the food supply in concert with an industrialized food system that produced and marketed convenient, highly processed foods from cheap agricultural inputs. Such foods often contain high amounts of salt, sugar, fat, and flavor additives and are engineered to have supernormal appetitive properties driving increased consumption. Ubiquitous access to convenient and inexpensive food also changed normative eating behavior, with more people snacking, eating in restaurants, and spending less time preparing meals at home. While such changes in the food environment provide a likely explanation of the obesity epidemic, definitive scientific demonstration is hindered by the difficulty in experimentally isolating and manipulating important variables at the population level.     

Plant Immune Responses Against Viruses: How Does a Virus Cause Disease?

Plants respond to pathogens using elaborate networks of genetic interactions. Recently, significant progress has been made in understanding RNA silencing and how viruses counter this apparently ubiquitous antiviral defense. In addition, plants also induce hypersensitive and systemic acquired resistance responses, which together limit the virus to infected cells and impart resistance to the noninfected tissues. Molecular processes such as the ubiquitin proteasome system and DNA methylation are also critical to antiviral defenses. Here, we provide a summary and update of advances in plant antiviral immune responses, beyond RNA silencing mechanisms—advances that went relatively unnoticed in the realm of RNA silencing and nonviral immune responses. We also document the rise of Brachypodium and Setaria species as model grasses to study antiviral responses in Poaceae, aspects that have been relatively understudied, despite grasses being the primary source of our calories, as well as animal feed, forage, recreation, and biofuel needs in the 21st century. Finally, we outline critical gaps, future prospects, and considerations central to studying plant antiviral immunity. To promote an integrated model of plant immunity, we discuss analogous viral and nonviral immune concepts and propose working definitions of viral effectors, effector-triggered immunity, and viral pathogen-triggered immunity.     

Macrophage-expressed IFN-β Contributes to Apoptotic Alveolar Epithelial Cell Injury in Severe Influenza Virus Pneumonia

Influenza viruses (IV) cause pneumonia in humans with progression to lung failure and fatal outcome. Dysregulated release of cytokines including type I interferons (IFNs) has been attributed a crucial role in immune-mediated pulmonary injury during severe IV infection. Using ex vivo and in vivo IV infection models, we demonstrate that alveolar macrophage (AM)-expressed IFN-β significantly contributes to IV-induced alveolar epithelial cell (AEC) injury by autocrine induction of the pro-apoptotic factor TNF-related apoptosis-inducing ligand (TRAIL). Of note, TRAIL was highly upregulated in and released from AM of patients with pandemic H1N1 IV-induced acute lung injury. Elucidating the cell-specific underlying signalling pathways revealed that IV infection induced IFN-β release in AM in a protein kinase R- (PKR-) and NF-κB-dependent way. Bone marrow chimeric mice lacking these signalling mediators in resident and lung-recruited AM and mice subjected to alveolar neutralization of IFN-β and TRAIL displayed reduced alveolar epithelial cell apoptosis and attenuated lung injury during severe IV pneumonia. Together, we demonstrate that macrophage-released type I IFNs, apart from their well-known anti-viral properties, contribute to IV-induced AEC damage and lung injury by autocrine induction of the pro-apoptotic factor TRAIL. Our data suggest that therapeutic targeting of the macrophage IFN-β-TRAIL axis might represent a promising strategy to attenuate IV-induced acute lung injury.     

Did evolution leap to create the protein universe?

The genomes of over 60 organisms from all three kingdoms of life are now entirely sequenced. In many respects, the inventory of proteins used in different kingdoms appears surprisingly similar. However, eukaryotes differ from other kingdoms in that they use many long proteins, and have more proteins with coiled-coil helices and with regions abundant in regular secondary structure. Particular structural domains are used in many pathways. Nevertheless, one domain tends to occur only once in one particular pathway. Many proteins do not have close homologues in different species (orphans) and there could even be folds that are specific to one species. This view implies that protein fold space is discrete. An alternative model suggests that structure space is continuous and that modern proteins evolved by aggregating fragments of ancient proteins. Either way, after having harvested proteomes by applying standard tools, the challenge now seems to be to develop better methods for comparative proteomics.     

Did detoxification processes cause complex life to emerge?

Excess oxygen is toxic for many cells and cell function can be disrupted by calcium, even if present in small amounts. Cells avoid the toxic effects of these substances by excreting oxygen-rich or Ca-containing molecules. The origin of macroscopic multi-celled animals (metazoans) can be attributed to the excretion of oxygen-rich collagen molecules (or their precursors) at a time when the seas were for the first time both oxygenated and sufficiently loaded with phosphorus for the energy (ATP) requirements of sizable metazoans. With subsequent increase of Ca in the marine environment, hard parts of CaCO₃ were produced. Excretion of oxygen in combination with abundant phosphorus permitted phosphate biomineralization. In this view, the most informative biological development during the late Neoproterozoic was not the emergence of metazoans but the initial construction of viable tissues. When tissue integrity is lost, whether due to low oxygen, collagen failure, injury, chemical insult or other reasons, individual cells are released from tissue-constraints. To survive, they may then revert to unicellular life-styles that emphasize cellular proliferation and variation. When this occurs in metazoans, the result may be cancer.     

Did geckos ride the Palawan raft to the Philippines?

Aim We examine the genetic diversity within the lizard genus Gekko in the Philippine islands to understand the role of geography and geological history in shaping species diversity in this group. We test multiple biogeographical hypotheses of species relationships, including the recently proposed Palawan Ark Hypothesis. Location Southeast Asia and the Philippines. Methods Samples of all island endemic and widespread Philippine Gekko species were collected and sequenced for one mitochondrial gene (NADH dehydrogenase subunit 2) and one nuclear gene (phosducin). We used maximum likelihood and Bayesian phylogenetic methods to derive the phylogeny. Divergence time analyses were used to estimate the time tree of Philippine Gekko in order to test biogeographical predictions of species relationships. The phylogenetic trees from the posterior distribution of the Bayesian analyses were used for testing biogeographical hypotheses. Haplotype networks were created for the widespread species Gekko mindorensis to explore genetic variation within recently divergent clades. Results Both maximum likelihood and Bayesian phylogenetic analyses indicated that Philippine Gekko species are a diverse clade with a long history in the archipelago. Ancestral range reconstruction and divergence time analyses suggest a Palawan microcontinental origin for this clade, coinciding with Palawan’s separation from Asia beginning 30 Ma, with subsequent diversification in the oceanic Philippine islands. The widespread species G. mindorensis and G. monarchus diversified in the late Miocene/early Pliocene and are potentially complexes of numerous undescribed species. Main conclusions The view of the Philippine islands as a ‘fringing archipelago’ does not explain the pattern of species diversity in the genus Gekko. Philippine Gekko species have diversified within the archipelago over millions of years of isolation, forming a large diverse group of endemic species. Furthermore, the Philippine radiation of gekkonid lizards demonstrates biogeographical patterns most consistent with stochastic colonization followed by in situ diversification. Our results reveal the need to consider deeper time geological processes and their potential role in the evolution of some Philippine terrestrial organisms.     

Zika Virus in Gabon (Central Africa) – 2007: A New Threat from Aedes albopictus?

Background

Chikungunya and dengue viruses emerged in Gabon in 2007, with large outbreaks primarily affecting the capital Libreville and several northern towns. Both viruses subsequently spread to the south-east of the country, with new outbreaks occurring in 2010. The mosquito species Aedes albopictus, that was known as a secondary vector for both viruses, recently invaded the country and was the primary vector involved in the Gabonese outbreaks. We conducted a retrospective study of human sera and mosquitoes collected in Gabon from 2007 to 2010, in order to identify other circulating arboviruses.

Methodology/Principal Findings

Sample collections, including 4312 sera from patients presenting with painful febrile disease, and 4665 mosquitoes belonging to 9 species, split into 247 pools (including 137 pools of Aedes albopictus), were screened with molecular biology methods. Five human sera and two Aedes albopictus pools, all sampled in an urban setting during the 2007 outbreak, were positive for the flavivirus Zika (ZIKV). The ratio of Aedes albopictus pools positive for ZIKV was similar to that positive for dengue virus during the concomitant dengue outbreak suggesting similar mosquito infection rates and, presumably, underlying a human ZIKV outbreak. ZIKV sequences from the envelope and NS3 genes were amplified from a human serum sample. Phylogenetic analysis placed the Gabonese ZIKV at a basal position in the African lineage, pointing to ancestral genetic diversification and spread.

Conclusions/Significance

We provide the first direct evidence of human ZIKV infections in Gabon, and its first occurrence in the Asian tiger mosquito, Aedes albopictus. These data reveal an unusual natural life cycle for this virus, occurring in an urban environment, and potentially representing a new emerging threat due to this novel association with a highly invasive vector whose geographic range is still expanding across the globe.     

Did Hydro-climatic Extremes,Positive Checks,and Economic Fluctuations Modulate the Epidemics Outbreaks in Late Imperial China?

Human Ecology - Empirical research has shown that climate-related variables, the decline in economic well-being, and the mutual reinforcement of positive checks are the primary drivers of epidemic...     

Why Did Bluetongue Spread the Way It Did? Environmental Factors Influencing the Velocity of Bluetongue Virus Serotype 8 Epizootic Wave in France

Understanding where and how fast an infectious disease will spread during an epidemic is critical for its control. However, the task is a challenging one as numerous factors may interact and drive the spread of a disease, specifically when vector-borne diseases are involved. We advocate the use of simultaneous autoregressive models to identify environmental features that significantly impact the velocity of disease spread. We illustrate this approach by exploring several environmental factors influencing the velocity of bluetongue (BT) spread in France during the 2007-2008 epizootic wave to determine which ones were the most important drivers. We used velocities of BT spread estimated in 4,495 municipalities and tested sixteen covariates defining five thematic groups of related variables: elevation, meteorological-related variables, landscape-related variables, host availability, and vaccination. We found that ecological factors associated with vector abundance and activity (elevation and meteorological-related variables), as well as with host availability, were important drivers of the spread of the disease. Specifically, the disease spread more slowly in areas with high elevation and when heavy rainfall associated with extreme temperature events occurred one or two months prior to the first clinical case. Moreover, the density of dairy cattle was correlated negatively with the velocity of BT spread. These findings add substantially to our understanding of BT spread in a temperate climate. Finally, the approach presented in this paper can be used with other infectious diseases, and provides a powerful tool to identify environmental features driving the velocity of disease spread.     

Refinement and Analysis of the Mature Zika Virus Cryo-EM Structure at 3.1 Å Resolution

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Did backcrossing contribute to the origin of hybrid edible bananas?

Background

Bananas and plantains (Musa spp.) provide a staple food for many millions of people living in the humid tropics. The cultivated varieties (cultivars) are seedless parthenocarpic clones of which the origin remains unclear. Many are believed to be diploid and polyploid hybrids involving the A genome diploid M. acuminata and the B genome M. balbisiana, with the hybrid genomes consisting of a simple combination of the parental ones. Thus the genomic constitution of the diploids has been classified as AB, and that of the triploids as AAB or ABB. However, the morphology of many accessions is biased towards either the A or B phenotype and does not conform to predictions based on these genomic formulae.

Scope

On the basis of published cytotypes (mitochondrial and chloroplast genomes), we speculate here that the hybrid banana genomes are unbalanced with respect to the parental ones, and/or that inter-genome translocation chromosomes are relatively common. We hypothesize that the evolution under domestication of cultivated banana hybrids is more likely to have passed through an intermediate hybrid, which was then involved in a variety of backcrossing events. We present experimental data supporting our hypothesis and we propose a set of experimental approaches to test it, thereby indicating other possibilities for explaining some of the unbalanced genome expressions. Progress in this area would not only throw more light on the origin of one of the most important crops, but provide data of general relevance for the evolution under domestication of many other important clonal crops. At the same time, a complex origin of the cultivated banana hybrids would imply a reconsideration of current breeding strategies.     

Virus adaptation to quantitative plant resistance: erosion or breakdown?

Adaptation of populations to new environments is frequently costly due to trade‐offs between life history traits, and consequently, parasites are expected to be locally adapted to sympatric hosts. Also, during adaptation to the host, an increase in parasite fitness could have direct consequences on its aggressiveness (i.e. the quantity of damages caused to the host by the virus). These two phenomena have been observed in the context of pathogen adaptation to host's qualitative and monogenic resistances. However, the ability of pathogens to adapt to quantitative polygenic plant resistances and the consequences of these potential adaptations on other pathogen life history traits remain to be evaluated. Potato virus Y and two pepper genotypes (one susceptible and one with quantitative resistance) were used, and experimental evolutions showed that adaptation to a quantitative resistance was possible and resulted in resistance breakdown. This adaptation was associated to a fitness cost on the susceptible cultivar, but had no consequence either in terms of aggressiveness, which could be explained by a high tolerance level, or in terms of aphid transmission efficiency. We concluded that quantitative resistances are not necessarily durable but management strategies mixing susceptible and resistant cultivars in space and/or in time should be useful to preserve their efficiency.     

Rearrangement of Actin Cytoskeleton by Zika Virus Infection Facilitates Blood–Testis Barrier Hyperpermeability

In recent years,various serious diseases caused by Zika virus (ZIKV) have made it impossible to be ignored.Confirmed existence of ZIKV in semen and sexually transmission of ZIKV suggested that it can break the blood–testis barrier (BTB),or Sertoli cell barrier (SCB).However,little is known about the underlying mechanism.In this study,interaction between actin,an important component of the SCB,and ZIKV envelope (E) protein domain Ⅲ (EDⅢ) was inferred from coimmunoprecipitation (Co-IP) liquid chromatography–tandem mass spectrometry (LC–MS/MS) analysis.Confocal microscopy confirmed the role of actin filaments (F-actin) in ZIKV infection,during which part of the stress fibers,the bundles that constituted by paralleled actin filaments,were disrupted and presented in the cell periphery.Colocalization of E and reorganized actin filaments in the cell periphery of transfected Sertoli cells suggests a participation of ZIKV E protein in ZIKV-induced F-actin rearrangement.Perturbation of F-actin by cytochalasin D (CytoD) or Jasplakinolide (Jas)enhanced the infection of ZIKV.More importantly,the transepithelial electrical resistance (TEER) of an in vitro mouse SCB (mSCB) model declined with the progression of ZIKV infection or overexpression of E protein.Co-IP and confocal microscopy analyses revealed that the interaction between F-actin and tight junction protein ZO-1 was reduced after ZIKV infection or E protein overexpression,highlighting the role of E protein in ZIKV-induced disruption of the BTB.We conclude that the interaction between ZIKV E and F-actin leads to the reorganization of F-actin network,thereby compromising BTB integrity.     

Does Intuition Cause Cooperation?

Recently, researchers claimed that people are intuitively inclined to cooperate with reflection causing them to behave selfishly. Empirical support for this claim came from experiments using a 4-player public goods game with a marginal return of 0.5 showing that people contributed more money to a common project when they had to decide quickly (i.e., a decision based on intuition) than when they were instructed to reflect and decide slowly. This intuitive-cooperation effect is of high scientific and practical importance because it argues against a central assumption of traditional economic and evolutionary models. The first experiment of present study was set up to examine the generality of the intuitive-cooperation effect and to further validate the experimental task producing the effect. In Experiment 1, we investigated Amazon Mechanical Turk (AMT) workers'' contributions to a 4-player public goods game with a marginal return of 0.5 while we manipulated the knowledge about the other players'' contribution to the public goods game (contribution known vs. contribution unknown), the identity of the other players (humans vs. computers randomly generating contributions) and the time constraint (time pressure/intuition vs. forced delay/reflection). However, the results of Experiment 1 failed to reveal an intuitive-cooperation effect. Furthermore, four subsequent direct replications attempts with AMT workers (Experiments 2a, 2b, 2c and Experiment 3, which was conducted with naïve/inexperienced participants) also failed to demonstrate intuitive-cooperation effects. Taken together, the results of the present study could not corroborate the idea that people are intuitively cooperative, hence suggesting that the theoretical relationship between intuition and cooperation should be further scrutinized.