Balancing Detection and Eradication for Control of Epidemics: Sudden Oak Death in Mixed-Species Stands

Culling of infected individuals is a widely used measure for the control of several plant and animal pathogens but culling first requires detection of often cryptically-infected hosts. In this paper, we address the problem of how to allocate resources between detection and culling when the budget for disease management is limited. The results are generic but we motivate the problem for the control of a botanical epidemic in a natural ecosystem: sudden oak death in mixed evergreen forests in coastal California, in which species composition is generally dominated by a spreader species (bay laurel) and a second host species (coast live oak) that is an epidemiological dead-end in that it does not transmit infection but which is frequently a target for preservation. Using a combination of an epidemiological model for two host species with a common pathogen together with optimal control theory we address the problem of how to balance the allocation of resources for detection and epidemic control in order to preserve both host species in the ecosystem. Contrary to simple expectations our results show that an intermediate level of detection is optimal. Low levels of detection, characteristic of low effort expended on searching and detection of diseased trees, and high detection levels, exemplified by the deployment of large amounts of resources to identify diseased trees, fail to bring the epidemic under control. Importantly, we show that a slight change in the balance between the resources allocated to detection and those allocated to control may lead to drastic inefficiencies in control strategies. The results hold when quarantine is introduced to reduce the ingress of infected material into the region of interest

3-O-(3′,3′-Dimethysuccinyl) Betulinic Acid Inhibits Maturation of the Human Immunodeficiency Virus Type 1 Gag Precursor Assembled In Vitro

3-O-(3′,3′-Dimethysuccinyl) betulinic acid (PA-457) has been shown to potently inhibit human immunodeficiency virus (HIV) replication in culture. In contrast to inhibitors that act upon the viral proteinase, PA-457 appears to block only the final maturational cleavage of p25CA-p2 to p24CA. However, attempts to replicate this effect in vitro using recombinant Gag have failed, leading to the hypothesis that activity is dependent upon the assembly state of Gag. Using a synthesis/assembly system for chimeric HIV type 1 Gag proteins, we have replicated the activity of PA-457 in vitro. The processing of assembled chimeric Gag can be inhibited by the addition of drug with only the final cleavage of p25CA-p2 to p24CA blocked. Consistent with our hypothesis and with previous findings, inhibition appears specific to Gag assembled into an immature capsid-like structure, since synthetic Gag that remains unassembled is properly processed in the presence of the compound. To further analyze the authenticity of the assay, PA-457 was tested in parallel with its inactive parental compound, betulinic acid. Betulinic acid had no effect upon p25 processing in this system. Analysis of a PA-457-resistant mutant, A1V, in this system pointed to more rapid cleavage as a possible mechanism for resistance. However, characterization of additional mutations at the cleavage site and in p2 suggests that resistance does not strictly correlate with the rate of cleavage. With the establishment of an in vitro assay for the detection of PA-457 activity, a more detailed characterization of its mechanism of action will be possible

Transcriptome of American Oysters, \u3cem\u3eCrassostrea virginica\u3c/em\u3e, in Response to Bacterial Challenge: Insights into Potential Mechanisms of Disease Resistance

The American oyster Crassostrea virginica, an ecologically and economically important estuarine organism, can suffer high mortalities in areas in the Northeast United States due to Roseovarius Oyster Disease (ROD), caused by the gram-negative bacterial pathogen Roseovarius crassostreae. The goals of this research were to provide insights into: 1) the responses of American oysters to R. crassostreae, and 2) potential mechanisms of resistance or susceptibility to ROD. The responses of oysters to bacterial challenge were characterized by exposing oysters from ROD-resistant and susceptible families to R. crassostreae, followed by high-throughput sequencing of cDNA samples from various timepoints after disease challenge. Sequence data was assembled into a reference transcriptome and analyzed through differential gene expression and functional enrichment to uncover genes and processes potentially involved in responses to ROD in the American oyster. While susceptible oysters experienced constant levels of mortality when challenged with R. crassostreae, resistant oysters showed levels of mortality similar to non-challenged oysters. Oysters exposed to R. crassostreae showed differential expression of transcripts involved in immune recognition, signaling, protease inhibition, detoxification, and apoptosis. Transcripts involved in metabolism were enriched in susceptible oysters, suggesting that bacterial infection places a large metabolic demand on these oysters. Transcripts differentially expressed in resistant oysters in response to infection included the immune modulators IL-17 and arginase, as well as several genes involved in extracellular matrix remodeling. The identification of potential genes and processes responsible for defense against R. crassostreae in the American oyster provides insights into potential mechanisms of disease resistance