Powassan virus is an emerging tick-borne virus of concern for public health, but very little is known about its transmission patterns and ecology. Here, we expanded the genomic dataset by sequencing 279 Powassan viruses isolated from Ixodes scapularis ticks from the northeastern United States. Our phylogeographic reconstructions revealed that Powassan virus lineage II was likely introduced or emerged from a relict population in the Northeast between 1940-1975. Sequences strongly clustered by sampling location, suggesting a highly focal geographical distribution. Our analyses further indicated that Powassan virus lineage II emerged in the northeastern U.S. mostly following a south to north pattern, with a weighted lineage dispersal velocity of ~3 km/year. Since the emergence in the Northeast, we found an overall increase in the effective population size of Powassan virus lineage II, but with growth stagnating during recent years. The cascading effect of population expansion of white-tailed deer and I. scapularis populations likely facilitated the emergence of Powassan virus in the northeastern U.S. Significance statement Our work provides important fundamental insights in the local transmission dynamics of an emerging tick-borne pathogen of public health concern. Without the availability of vaccines or specific treatments, prevention of Powassan virus infection is dependent on education and control. We identified that Powassan virus is maintained in highly localized transmission foci that have been maintained for several years, without introductions of new virus clades. This provides both opportunities for better education about high risk areas and effective targeted control in Powassan virus foci with a long lasting impact.

/pdf/phylogeographic-reconstruction-of-the-emergence-and-spread-2l8dmad9.pdf

Phylogeographic reconstruction of the emergence and spread of Powassan virus in the northeastern United States

Lassa fever (LF) is a potentially lethal viral haemorrhagic infection of humans caused by Lassa mammarenavirus (LASV). It is an important endemic zoonotic disease in West Africa with growing evidence for increasing frequency and sizes of outbreaks. Phylogeographic and molecular epidemiology methods have projected expansion of the Lassa fever endemic zone in the context of future global change. The Natal multimammate mouse (Mastomys natalensis) is the predominant LASV reservoir, with few studies investigating the role of other animal species. To explore host sequencing biases, all LASV nucleotide sequences and associated metadata available on GenBank (n = 2,298) were retrieved. Most data originated from Nigeria (54%), Guinea (20%) and Sierra Leone (14%). Data from non-human hosts (n = 703) were limited and only 69 sequences encompassed complete genes. We found a strong positive correlation between the number of confirmed human cases and sequences at the country level (r = 0.93 (95% Confidence Interval = 0.71 - 0.98), p < 0.001) but no correlation exists between confirmed cases and the number of available rodent sequences (r = -0.019 (95% C.I. -0.71 - 0.69), p = 0.96). Spatial modelling of sequencing effort highlighted current biases in locations of available sequences, with increased effort observed in Southern Guinea and Southern Nigeria. Phylogenetic analyses showed geographic clustering of LASV lineages, suggestive of isolated events of human-to-rodent transmission and the emergence of currently circulating strains of LASV from the year 1498 in Nigeria. Overall, the current study highlights significant geographic limitations in LASV surveillance, particularly, in non-human hosts. Further investigation of the non-human reservoir of LASV, alongside expanded surveillance, are required for precise characterisation of the emergence and dispersal of LASV. Accurate surveillance of LASV circulation in non-human hosts is vital to guide early detection and initiation of public health interventions for future Lassa fever outbreaks.

/pdf/current-sampling-and-sequencing-biases-of-lassa-25squ29h.pdf

Current sampling and sequencing biases of Lassa mammarenavirus limit inference from phylogeography and molecular epidemiology in Lassa fever endemic regions.

Biosecurity and disease monitoring

Lassa fever, an endemic viral hemorrhagic fever in West Africa, is attributed to the Lassa virus as its causative agent, and this disease has led to the untimely death of many people in the affected areas. At present, the available treatment options for Lassa fever are limited and there is need for new drugs. This study aims to use computational tools to predict the efficacy of small molecules that can target the Lassa fever virus glycoprotein which is essential for viral entry into host cells. This study uses quantitative structure activity relationship (QSAR) to reduce the cost and time of preclinical evaluation of potential drugs. This study retrieves 7620 molecules that can inhibit Lassa virus glycoprotein from ChEMBL database and builds a regression model with random forest algorithm. Its performance was compared with other regression models by using lazy predict, and random forest performed better than most of the regression models. The coefficient of determination r 2 are 0.93 and 0.56 for the training and test set and root mean square error (RMSE) of 0.32 and 0.77 for the training set and test set, respectively. In conclusion, the model satisfies the acceptable QSAR model.

Computational prediction of small molecules targeting Lassa fever drug target using quantitative structure activity relationship (QSAR) and random forest algorithm

Lassa fever is listed among the diseases that pose the greatest risks to public health by the World Health Organization. This severe viral hemorrhagic fever is caused by Lassa virus, a zoonotic pathogen that repeatedly spills over to humans from its rodent reservoirs. It is currently not known how climate change, transformations in land use, and human population growth could affect the endemic area of this virus, currently limited to parts of West Africa. By exploring the environmental data associated with virus occurrence, we show how temperature, precipitation and the presence of pastures determine ecological suitability for virus circulation. We project that regions in Central and East Africa will likely become suitable for Lassa virus over the next decades and estimate that the total population living in areas suitable for Lassa virus may grow from about 100 million to 700 million by 2070. By analysing geotagged viral genomes, we find that in the event of Lassa virus being introduced into a new suitable region, its spread might remain spatially limited over the first decades. Our results highlight how the endemic area of Lassa virus may expand well beyond West Africa in the next decades due to human impact on the environment, putting hundreds of million more people at risk of infection.

/pdf/predicting-the-evolution-of-lassa-virus-endemic-area-and-4flyg5qmx0.pdf

Predicting the evolution of Lassa Virus endemic area and population at risk over the next decades

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Predicting the evolution of Lassa Virus endemic area and population at risk over the next decades