1. Virus Ecology Section, Laboratory of Virology, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Rocky Mountain Laboratories, Hamilton, MT 59840, USA
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Dr. Stephanie Seifert
1. Virus Ecology Section, Laboratory of Virology, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Rocky Mountain Laboratories, Hamilton, MT 59840, USA
Maxent, one of the most commonly used methods for inferring species distributions and environmental tolerances from occurrence data, allows users to fit models of arbitrary complexity. Model complexity is typically constrained via a process known as L1 regularization, but at present little guidance is available for setting the appropriate level of regularization, and the effects of inappropriately complex or simple models are largely unknown. In this study, we demonstrate the use of information criterion approaches to setting regularization in Maxent, and we compare models selected using information criteria to models selected using other criteria that are common in the literature. We evaluate model performance using occurrence data generated from a known “true” initial Maxent model, using several different metrics for model quality and transferability. We demonstrate that models that are inappropriately complex or inappropriately simple show reduced ability to infer habitat quality, reduced ability to infer the relative importance of variables in constraining species' distributions, and reduced transferability to other time periods. We also demonstrate that information criteria may offer significant advantages over the methods commonly used in the literature.
Diurnal temperature fluctuations can fundamentally alter mosquito biology and mosquito-virus interactions in ways that impact pathogen transmission. We investigated the effect of two daily fluctuating temperature profiles on Aedes aegypti vector competence for dengue virus (DENV) serotype-1. A large diurnal temperature range of 18.6°C around a 26°C mean, corresponding with the low DENV transmission season in northwestern Thailand, reduced midgut infection rates and tended to extend the virus extrinsic incubation period. Dissemination was first observed at day 7 under small fluctuations (7.6°C; corresponding with high DENV transmission) and constant control temperature, but not until Day 11 for the large diurnal temperature range. Results indicate that female Ae. aegypti in northwest Thailand are less likely to transmit DENV during the low than high transmission season because of reduced DENV susceptibility and extended virus extrinsic incubation period. Better understanding of DENV transmission dynamics will come with improved knowledge of temperature effects on mosquito-virus interactions.
Middle East Respiratory Syndrome Coronavirus (MERS-CoV) likely originated in bats and passed to humans through dromedary camels; however, the genetic mechanisms underlying cross-species adaptation remain poorly understood. Variation in the host receptor, dipeptidyl peptidase 4 (DPP4), can block the interaction with the MERS-CoV spike protein and form a species barrier to infection. To better understand the species adaptability of MERS-CoV, we identified a suboptimal species-derived variant of DPP4 to study viral adaption. Passaging virus on cells expressing this DPP4 variant led to accumulation of mutations in the viral spike which increased replication. Parallel passages revealed distinct paths of viral adaptation to the same DPP4 variant. Structural analysis and functional assays showed that these mutations enhanced viral entry with suboptimal DPP4 by altering the surface charge of spike. These findings demonstrate that MERS-CoV spike can utilize multiple paths to rapidly adapt to novel species variation in DPP4.