Genome Sequence Analysis of Dengue Virus 1 Isolated in Key West, Florida

Dengue virus (DENV) is transmitted to humans through the bite of mosquitoes. In November 2010, a dengue outbreak was reported in Monroe County in southern Florida (FL), including greater than 20 confirmed human cases. The virus collected from the human cases was verified as DENV serotype 1 (DENV-1) and one isolate was provided for sequence analysis. RNA was extracted from the DENV-1 isolate and was used in reverse transcription polymerase chain reaction (RT-PCR) to amplify PCR fragments to sequence. Nucleic acid primers were designed to generate overlapping PCR fragments that covered the entire genome. The DENV-1 isolate found in Key West (KW), FL was sequenced for whole genome characterization. Sequence assembly, Genbank searches, and recombination analyses were performed to verify the identity of the genome sequences and to determine percent similarity to known DENV-1 sequences. We show that the KW DENV-1 strain is 99% identical to Nicaraguan and Mexican DENV-1 strains. Phylogenetic and recombination analyses suggest that the DENV-1 isolated in KW originated from Nicaragua (NI) and the KW strain may circulate in KW. Also, recombination analysis results detected recombination events in the KW strain compared to DENV-1 strains from Puerto Rico. We evaluate the relative growth of KW strain of DENV-1 compared to other dengue viruses to determine whether the underlying genetics of the strain is associated with a replicative advantage, an important consideration since local transmission of DENV may result because domestic tourism can spread DENVs

Exploiting evolutionary steering to induce collateral drug sensitivity in cancer

Drug resistance mediated by clonal evolution is arguably the biggest problem in cancer therapy today. However, evolving resistance to one drug may come at a cost of decreased fecundity or increased sensitivity to another drug. These evolutionary trade-offs can be exploited using 'evolutionary steering' to control the tumour population and delay resistance. However, recapitulating cancer evolutionary dynamics experimentally remains challenging. Here, we present an approach for evolutionary steering based on a combination of single-cell barcoding, large populations of 108-109 cells grown without re-plating, longitudinal non-destructive monitoring of cancer clones, and mathematical modelling of tumour evolution. We demonstrate evolutionary steering in a lung cancer model, showing that it shifts the clonal composition of the tumour in our favour, leading to collateral sensitivity and proliferative costs. Genomic profiling revealed some of the mechanisms that drive evolved sensitivity. This approach allows modelling evolutionary steering strategies that can potentially control treatment resistance

Meteorological variables and mosquito monitoring are good predictors for infestation trends of Aedes aegypti, the vector of dengue, chikungunya and Zika

BACKGROUND: Aedes aegypti is an important vector for arboviroses and widely distributed throughout the world. Climatic factors can influence vector population dynamics and, consequently, disease transmission. The aim of this study was to characterize the temporal dynamics of an Ae. aegypti population and dengue cases and to investigate the relationship between meteorological variables and mosquito infestation. METHODS: We monitored and analyzed the adult female Ae. aegypti population, the dengue-fever vector, in Porto Alegre, a subtropical city in Brazil using the MI-Dengue system (intelligent dengue monitoring). This system uses sticky traps to monitor weekly infestation indices. We fitted generalized additive models (GAM) with climate variables including precipitation, temperature and humidity, and a GAM that additionally included mosquito abundance in the previous week as an explanatory variable. Logistic regression was used to evaluate the effect of adult mosquito infestation on the probability of dengue occurrence. RESULTS: Adult mosquito abundance was strongly seasonal, with low infestation indices during the winters and high infestation during the summers. Weekly minimum temperatures above 18 °C were strongly associated with increased mosquito abundance, whereas humidity above 75% had a negative effect on abundance. The GAM model that included adult mosquito infestation in the previous week adjusted and predicted the observed data much better than the model which included only meteorological predictor variables. Dengue was also seasonal and 98% of all cases occurred at times of high adult Ae. aegypti infestation. The probability of dengue occurrence increased by 25%, when the mean number of adult mosquitos caught by monitoring traps increased by 0.1 mosquitoes per week. CONCLUSIONS: The results suggest that continuous monitoring of dengue vector population allows for more reliable predictions of infestation indices. The adult mosquito infestation index was a good predictor of dengue occurrence. Weekly adult dengue vector monitoring is a helpful dengue control strategy in subtropical Brazilian cities. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13071-017-2025-8) contains supplementary material, which is available to authorized users