Humidity – The overlooked variable in the thermal biology of mosquito-borne disease

Vector-borne diseases cause significant financial and human loss, with billions of dollars spent on control. Arthropod vectors experience a complex suite of environmental factors that affect fitness, population growth and species interactions across multiple spatial and temporal scales. Temperature and water availability are two of the most important abiotic variables influencing their distributions and abundances. While extensive research on temperature exists, the influence of humidity on vector and pathogen parameters affecting disease dynamics are less understood. Humidity is often underemphasized, and when considered, is often treated as independent of temperature even though desiccation likely contributes to declines in trait performance at warmer temperatures. This Perspectives explores how humidity shapes the thermal performance of mosquito-borne pathogen transmission. We summarize what is known about its effects and propose a conceptual model for how temperature and humidity interact to shape the range of temperatures across which mosquitoes persist and achieve high transmission potential. We discuss how failing to account for these interactions hinders efforts to forecast transmission dynamics and respond to epidemics of mosquito-borne infections. We outline future research areas that will ground the effects of humidity on the thermal biology of pathogen transmission in a theoretical and empirical framework to improve spatial and temporal prediction of vector-borne pathogen transmission.     

Herpes Simplex Virus Is Equipped with RNA- and Protein-Based Mechanisms To Repress Expression of ATRX, an Effector of Intrinsic Immunity

Intrinsic immunity is a first-line intracellular defense against virus infection, and viruses have evolved mechanisms to counteract it. During herpes simplex virus (HSV) infection, nuclear domain 10 (ND10) components localize adjacent to incoming viral genomes and generate a repressive environment for viral gene expression. Here, we found that the ND10 component, alpha-thalassemia/mental retardation syndrome X-linked (ATRX) protein, is predicted to be a target of HSV-1 miR-H1 and HSV-2 miR-H6. These microRNAs (miRNAs) share a seed sequence and are abundant during lytic infection. Mimics of both miRNAs could deplete endogenous ATRX, and an miR-H1 mimic could repress the expression of a reporter linked to the 3' untranslated region of ATRX mRNA, identifying a cellular mRNA targeted by an HSV miRNA. Interestingly, ATRX protein and its mRNA were depleted in cells lytically infected with HSV, and ATRX protein was also depleted in cells infected with human cytomegalovirus. However, infection with an HSV-1 mutant lacking miR-H1 still resulted in ATRX depletion. This depletion was sensitive to a proteasome inhibitor and was largely ablated by a deletion of the gene encoding the immediate-early ICP0 protein. Additionally, a deletion of the gene encoding the tegument protein Vhs ablated most of the depletion of ATRX mRNA. Thus, HSV is equipped with multiple mechanisms to limit the expression of ATRX. As ATRX is implicated in repression of lytic viral gene expression, our results suggest roles for these different mechanisms during various phases of HSV infection.     

An Integrated Approach to Modeling Grazing Pressure in Pastoral Systems: The Case of the Logone Floodplain (Cameroon)

The discussion about the impact of pastoral systems on ecosystems has been profoundly shaped by Hardin’s “tragedy of the commons” argument that held pastoralists responsible for overgrazing the range. Recent studies have shown that grazing ecosystems are much more complex and dynamic than was previously assumed and that pastoralists adaptively manage these systems. However, we still have little understanding how everyday herding affects ecosystems at the landscape level. We conducted a study of daily herd movements and grazing strategies in a mobile pastoral system in the Logone floodplain, Cameroon. We integrated GPS/GIS technology, video recordings of animal behavior, and ethnographic methods to develop a more accurate measurement of grazing pressure that takes into account both livestock densities and grazing behavior. We used the resulting grazing pressure data to evaluate existing conceptual models of grazing pressure at a landscape level. We found that models that predict that grazing pressure is skewed towards the direction of water most accurately reflect the situation in the Logone floodplain in the dry season. However, we found that the higher grazing pressure is not only the result of a higher density of cattle but also a change in the grazing behavior of animals after watering. Finally, we caution that the models of grazing pressure in the dry season cannot simply be extrapolated to the landscape level because mobile pastoralists do not remain in one central place.     

Sex- and lineage-specific inheritance of depression-like behavior in the rat

The Wistar–Kyoto (WKY) rat exhibits physiological and behavioral similarities to endophenotypes of human depression. In the forced swim test (FST), a well-characterized antidepressant-reversible test for behavioral despair in rodents, WKYs express characteristics of behavioral despair; increased immobility, and decreased climbing. To map genetic loci linked to behavior in the FST, we conducted a quantitative trait loci (QTL) analysis of the segregating F2 generation of a WKY × Fisher 344 (F344) reciprocal intercross. Using linear-model-based genome scans to include covariate (sex or lineage)-by-QTL interaction effects, four significant QTL influencing climbing behavior were identified. In addition, we identified three, seven, and two suggestive QTL for climbing, immobility, and swimming, respectively. One of these loci was pleiotropic, affecting both immobility and climbing. As found in human linkage studies, several of these QTL showed sex- and/or lineage-dependent effects. A simultaneous search strategy identified three epistatic locus pairs for climbing. Multiple regression analysis was employed to characterize the joint contributions of these QTL and to clarify the sex- and lineage-dependent effects. As expected for complex traits, FST behavior is influenced by multiple QTL of small effect, each contributing 5%–10%, accounting for a total 10%–30% of the phenotypic variance. A number of loci mapped in this study share overlapping candidate regions with previously identified emotionality QTL in mice as well as with susceptibility loci recognized by linkage or genome scan analyses for major depression or bipolar disorder in humans. The presence of these loci across species suggests that these QTL may represent universal genetic factors contributing to mood disorders.     

DBA/2J Genetic Background Exacerbates Spontaneous Lethal Seizures but Lessens Amyloid Deposition in a Mouse Model of Alzheimer’s Disease

Alzheimer’s disease (AD) is a leading cause of dementia in the elderly and is characterized by amyloid plaques, neurofibrillary tangles (NFTs) and neuronal dysfunction. Early onset AD (EOAD) is commonly caused by mutations in amyloid precursor protein (APP) or genes involved in the processing of APP including the presenilins (e.g. PSEN1 or PSEN2). In general, mouse models relevant to EOAD recapitulate amyloidosis, show only limited amounts of NFTs and neuronal cell dysfunction and low but significant levels of seizure susceptibility. To investigate the effect of genetic background on these phenotypes, we generated APP^swe and PSEN1^de9 transgenic mice on the seizure prone inbred strain background, DBA/2J. Previous studies show that the DBA/2J genetic background modifies plaque deposition in the presence of mutant APP but the impact of PSEN1^de9 has not been tested. Our study shows that DBA/2J.APP^swePSEN1^de9 mice are significantly more prone to premature lethality, likely to due to lethal seizures, compared to B6.APP^swePSEN1^de9 mice—70% of DBA/2J.APP^swePSEN1^de9 mice die between 2-3 months of age. Of the DBA/2J.APP^swePSEN1^de9 mice that survived to 6 months of age, plaque deposition was greatly reduced compared to age-matched B6.APP^swePSEN1^de9 mice. The reduction in plaque deposition appears to be independent of microglia numbers, reactive astrocytosis and complement C5 activity.     

Construction and Immunogenicity Evaluation of Recombinant Influenza A Viruses Containing Chimeric Hemagglutinin Genes Derived from Genetically Divergent Influenza A H1N1 Subtype Viruses

Background and Objectives

Influenza A viruses cause highly contagious diseases in a variety of hosts, including humans and pigs. To develop a vaccine that can be broadly effective against genetically divergent strains of the virus, in this study we employed molecular breeding (DNA shuffling) technology to create a panel of chimeric HA genes.

Methods and Results

Each chimeric HA gene contained genetic elements from parental swine influenza A viruses that had a history of zoonotic transmission, and also from a 2009 pandemic virus. Each parental virus represents a major phylogenetic clade of influenza A H1N1 viruses. Nine shuffled HA constructs were initially screened for immunogenicity in mice by DNA immunization, and one chimeric HA (HA-129) was expressed on both a A/Puerto Rico/8/34 backbone with mutations associated with a live, attenuated phenotype (PR8_LAIV-129) and a A/swine/Texas/4199-2/98 backbone (TX98-129). When delivered to mice, the PR8_LAIV-129 induced antibodies against all four parental viruses, which was similar to the breadth of immunity observed when HA-129 was delivered as a DNA vaccine. This chimeric HA was then tested as a candidate vaccine in a nursery pig model, using inactivated TX98-129 virus as the backbone. The results demonstrate that pigs immunized with HA-129 developed antibodies against all four parental viruses, as well as additional primary swine H1N1 influenza virus field isolates.

Conclusion

This study established a platform for creating novel genes of influenza viruses using a molecular breeding approach, which will have important applications toward future development of broadly protective influenza virus vaccines.     

Francisella tularensis live vaccine strain induces macrophage alternative activation as a survival mechanism

Francisella tularensis (Ft), the causative agent of tularemia, elicits a potent inflammatory response early in infection, yet persists within host macrophages and can be lethal if left unchecked. We report in this study that Ft live vaccine strain (LVS) infection of murine macrophages induced TLR2-dependent expression of alternative activation markers that followed the appearance of classically activated markers. Intraperitoneal infection with Ft LVS also resulted in induction of alternatively activated macrophages (AA-Mphi). Induction of AA-Mphi by treatment of cells with rIL-4 or by infection with Ft LVS promoted replication of intracellular Ftn, in contrast to classically activated (IFN-gamma plus LPS) macrophages that promoted intracellular killing of Ft LVS. Ft LVS failed to induce alternative activation in IL-4Ralpha(-/-) or STAT6(-/-) macrophages and prolonged the classical inflammatory response in these cells, resulting in intracellular killing of Ft. Treatment of macrophages with anti-IL-4 and anti-IL-13 Ab blunted Ft-induced AA-Mphi differentiation and resulted in increased expression of IL-12 p70 and decreased bacterial replication. In vivo, Ft-infected IL-4Ralpha(-/-) mice exhibited increased survival compared with wild-type mice. Thus, redirection of macrophage differentiation by Ft LVS from a classical to an alternative activation state enables the organism to survive at the expense of the host.     

The relative importance of egg production rate, hatching success, hatching duration and egg sinking in population recruitment of two species of marine copepods

The disappearance of spawned copepod eggs can, at times, approach100% day^–1 and may be a bottleneck to population recruitmentof marine copepods. We examined the egg production rate andegg hatching success of Centropages hamatus and Temora longicomis(Copepoda: Calanoida) on natural diets, and the role of delayedhatching combined with high sinking rates in removing theireggs from the water column. Cumulative hatching success withinIS days was consistently high from March to June 1996: