Impact of Unexplored Data Sources on the Historical Distribution of Three Vector Tick Species in Illinois.

We updated the Illinois historical (1905-December 2017) distribution and status (not reported, reported or established) maps for Amblyomma americanum (L.) (Acari: Ixodidae), Dermacentor variabilis (Say) (Acari: Ixodidae), and Ixodes scapularis (Say) (Acari: Ixodidae) by compiling publicly available, previously unexplored or newly identified published and unpublished data (untapped data). Primary data sources offered specific tick-level information, followed by secondary and tertiary data sources. For A. americanum, D. variabilis, and I. scapularis, primary data contributed to 90% (4,045/4,482), 80% (2,124/2,640), and 32% (3,490/10,898) tick records vs 10%, 20%, and 68%, respectively from secondary data; primary data updated status in 95% (62/65), 94% (51/54) and in 90% (9/10) of the updated counties for each of these tick species; by 1985 there were tick records in 6%, 68%, and 0% of the counties, compared to 20%, 72%, and 58% by 2004, and 77%, 96%, and 75% of the counties by 2017, respectively for A. americanum, D. variabilis, and I. scapularis. We document the loss of tick records due to unidentified, not cataloged tick collections, unidentified ticks in tick collections, unpublished data or manuscripts without specific county location, and tick-level information, to determine distribution and status. In light of the increase in tick-borne illnesses, updates in historical distributions and status maps help researchers and health officials to identify risk areas for a tick encounter and suggest targeted areas for public outreach and surveillance efforts for ticks and tick-borne diseases. There is a need for a systematic, national vector surveillance program to support research and public health responses to tick expansions and tick-borne diseases.

Modeling reproduction of whitetail deer and its applications.

Many environmental factors, such as annual precipitation, temperature variations, and the embedded stochasticity of natural systems, affect resource availability from one region to the next, such that animal survival and reproduction rates differ by region. For species exhibiting phenotypic plasticity, embedding phenotypes in a model of population dynamics becomes important, as region-driven plastic responses play a significant role when estimating parameters values. In this paper, we discuss how to include observable characteristics and climate patterns in estimates of reproduction rates of whitetail deer (Odocoileus virginianus). Using many studies already available in the literature, we establish a strong correlation between reproduction rate and both body weight and USDA plant hardiness zone. We demonstrate the accuracy of the estimated whitetail deer fecundity rates for various geographical regions in North America and show that Bergmann's rule is necessary to maintain similar biological fitness between various spatial distributions of deer populations. We demonstrate that the standard deviation of the weight distribution has almost no effect on reproduction rate estimates for adult deer populations. However, statistical analysis reveals sensitivity of fawn reproduction rates to environmental stochasticity. We incorporate the reproduction function in a stage- and gender-based model and prove the existence of a stable solution. Finally, we demonstrate a possible application of the model using harvested deer weights, without collecting reproduction data directly.

Vesicular Stomatitis Virus Pseudotyped with Ebola Virus Glycoprotein Serves as a Protective, Noninfectious Vaccine against Ebola Virus Challenge in Mice.

The recent Ebola virus (EBOV) epidemic in West Africa demonstrates the potential for a significant public health burden caused by filoviral infections. No vaccine or antiviral is currently FDA approved. To expand the vaccine options potentially available, we assessed protection conferred by an EBOV vaccine composed of vesicular stomatitis virus pseudovirions that lack native G glycoprotein (VSVΔG) and bear EBOV glycoprotein (GP). These pseudovirions mediate a single round of infection. Both single-dose and prime/boost vaccination regimens protected mice against lethal challenge with mouse-adapted Ebola virus (ma-EBOV) in a dose-dependent manner. The prime/boost regimen provided significantly better protection than a single dose. As N-linked glycans are thought to shield conserved regions of the EBOV GP receptor-binding domain (RBD), thereby blocking epitopes within the RBD, we also tested whether VSVΔG bearing EBOV GPs that lack GP1 N-linked glycans provided effective immunity against challenge with ma-EBOV or a more distantly related virus, Sudan virus. Using a prime/boost strategy, high doses of GP/VSVΔG partially or fully denuded of N-linked glycans on GP1 protected mice against ma-EBOV challenge, but these mutants were no more effective than wild-type (WT) GP/VSVΔG and did not provide cross protection against Sudan virus. As reported for other EBOV vaccine platforms, the protection conferred correlated with the quantity of EBOV GP-specific Ig produced but not with the production of neutralizing antibodies. Our results show that EBOV GP/VSVΔG pseudovirions serve as a successful vaccination platform in a rodent model of Ebola virus disease and that GP1 N-glycan loss does not influence immunogenicity or vaccination success.IMPORTANCE The West African Ebola virus epidemic was the largest to date, with more than 28,000 people infected. No FDA-approved vaccines are yet available, but in a trial vaccination strategy in West Africa, recombinant, infectious VSV encoding the Ebola virus glycoprotein effectively prevented virus-associated disease. VSVΔG pseudovirion vaccines may prove as efficacious and have better safety, but they have not been tested to date. Thus, we tested the efficacy of VSVΔG pseudovirions bearing Ebola virus glycoprotein as a vaccine platform. We found that wild-type Ebola virus glycoprotein, in the context of this platform, provides robust protection of EBOV-challenged mice. Further, we found that removal of the heavy glycan shield surrounding conserved regions of the glycoprotein does not enhance vaccine efficacy.

Interferon-γ Inhibits Ebola Virus Infection.

Ebola virus outbreaks, such as the 2014 Makona epidemic in West Africa, are episodic and deadly. Filovirus antivirals are currently not clinically available. Our findings suggest interferon gamma, an FDA-approved drug, may serve as a novel and effective prophylactic or treatment option. Using mouse-adapted Ebola virus, we found that murine interferon gamma administered 24 hours before or after infection robustly protects lethally-challenged mice and reduces morbidity and serum viral titers. Furthermore, we demonstrated that interferon gamma profoundly inhibits Ebola virus infection of macrophages, an early cellular target of infection. As early as six hours following in vitro infection, Ebola virus RNA levels in interferon gamma-treated macrophages were lower than in infected, untreated cells. Addition of the protein synthesis inhibitor, cycloheximide, to interferon gamma-treated macrophages did not further reduce viral RNA levels, suggesting that interferon gamma blocks life cycle events that require protein synthesis such as virus replication. Microarray studies with interferon gamma-treated human macrophages identified more than 160 interferon-stimulated genes. Ectopic expression of a select group of these genes inhibited Ebola virus infection. These studies provide new potential avenues for antiviral targeting as these genes that have not previously appreciated to inhibit negative strand RNA viruses and specifically Ebola virus infection. As treatment of interferon gamma robustly protects mice from lethal Ebola virus infection, we propose that interferon gamma should be further evaluated for its efficacy as a prophylactic and/or therapeutic strategy against filoviruses. Use of this FDA-approved drug could rapidly be deployed during future outbreaks.

The Nectin-4/Afadin Protein Complex and Intercellular Membrane Pores Contribute to Rapid Spread of Measles Virus in Primary Human Airway Epithelia.

UNLABELLED: The discovery that measles virus (MV) uses the adherens junction protein nectin-4 as its epithelial receptor provides a new vantage point from which to characterize its rapid spread in the airway epithelium. We show here that in well-differentiated primary cultures of airway epithelial cells from human donors (HAE), MV infectious centers form rapidly and become larger than those of other respiratory pathogens: human respiratory syncytial virus, parainfluenza virus 5, and Sendai virus. While visible syncytia do not form after MV infection of HAE, the cytoplasm of an infected cell suddenly flows into an adjacent cell, as visualized through wild-type MV-expressed cytoplasmic green fluorescent protein (GFP). High-resolution video microscopy documents that GFP flows through openings that form on the lateral surfaces between columnar epithelial cells. To assess the relevance of the protein afadin, which connects nectin-4 to the actin cytoskeleton, we knocked down its mRNA. This resulted in more-limited infectious-center formation. We also generated a nectin-4 mutant without the afadin-binding site in its cytoplasmic tail. This mutant was less effective than wild-type human nectin-4 at promoting MV infection in primary cultures of porcine airway epithelia. Thus, in airway epithelial cells, MV spread requires the nectin-4/afadin complex and is based on cytoplasm transfer between columnar cells. Since the viral membrane fusion apparatus may open the passages that allow cytoplasm transfer, we refer to them as intercellular membrane pores. Virus-induced intercellular pores may contribute to extremely efficient measles contagion by promoting the rapid spread of the virus through the upper respiratory epithelium. IMPORTANCE: Measles virus (MV), while targeted for eradication, still causes about 120,000 deaths per year worldwide. The recent reemergence of measles in insufficiently vaccinated populations in Europe and North America reminds us that measles is extremely contagious, but the processes favoring its spread in the respiratory epithelium remain poorly defined. Here we characterize wild-type MV spread in well-differentiated primary cultures of human airway epithelial cells. We observed that viral infection promotes the flow of cytoplasmic contents from infected to proximal uninfected columnar epithelial cells. Cytoplasm flows through openings that form on the lateral surfaces. Infectious-center growth is facilitated by afadin, a protein connecting the adherens junction and the actin cytoskeleton. The viral fusion apparatus may open intercellular pores, and the cytoskeleton may stabilize them. Rapid homogenization of cytoplasmic contents in epithelial infectious centers may favor rapid spread and contribute to the extremely contagious nature of measles.