The Role of Human Transportation Networks in Mediating the Genetic Structure of Seasonal Influenza in the United States.

Recent studies have demonstrated the importance of accounting for human mobility networks when modeling epidemics in order to accurately predict spatial dynamics. However, little is known about the impact these movement networks have on the genetic structure of pathogen populations and whether these effects are scale-dependent. We investigated how human movement along the aviation and commuter networks contributed to intra-seasonal genetic structure of influenza A epidemics in the continental United States using spatially-referenced hemagglutinin nucleotide sequences collected from 2003-2013 for both the H3N2 and H1N1 subtypes. Comparative analysis of these transportation networks revealed that the commuter network is highly spatially-organized and more heavily traveled than the aviation network, which instead is characterized by high connectivity between all state pairs. We found that genetic distance between sequences often correlated with distance based on interstate commuter network connectivity for the H1N1 subtype, and that this correlation was not as prevalent when geographic distance or aviation network connectivity distance was assessed against genetic distance. However, these patterns were not as apparent for the H3N2 subtype at the scale of the continental United States. Finally, although sequences were spatially referenced at the level of the US state of collection, a community analysis based on county to county commuter connections revealed that commuting communities did not consistently align with state geographic boundaries, emphasizing the need for the greater availability of more specific sequence location data. Our results highlight the importance of utilizing host movement data in characterizing the underlying genetic structure of pathogen populations and demonstrate a need for a greater understanding of the differential effects of host movement networks on pathogen transmission at various spatial scales

Aviation (A) and commuter (B) network models for the continental US.

<p>Edge colors represent the number of individuals traveling between each state pair per day. Bar plots directly below each network depict the weight (total number of individuals moving in (colored red) and out (colored blue) of a state; top) and degree (total number of connections in (colored red) and out (colored blue) of a state; bottom) for each of that network’s nodes, ordered from left to right by the longitude of each state’s population center.</p

Mantel r correlation coefficients measuring the association between matrices of genetic, temporal, geographic, aviation network and commuter network distance for H1N1 sequences.

<p>Significant p-values are based on a Bonferroni correction, computed to account for multiple clade comparisons within a single season. When more than one distance metric is correlated with genetic distance, asterisks denote those metrics that remained significant after partial Mantel tests were conducted (at the p = 0.05 level).</p><p>⁺ Neither metric remained significant after a partial mantel test was performed (at the p = 0.05 level).</p><p>Mantel r correlation coefficients measuring the association between matrices of genetic, temporal, geographic, aviation network and commuter network distance for H1N1 sequences.</p

US commuting communities.

<p>Two realizations using the simulated annealing algorithm to partition the US into communities based on an unweighted network (A) and weighted network (B) of county-to-county commuter flows. Modularity is similar across all realizations for a given network type, although exact community compositions differ. In all realizations, community boundaries do not neatly coincide with state borders.</p

Phylogeography of rubella virus in Asia: Vaccination and demography shape synchronous outbreaks

© 2019 The Authors Rubella virus causes mild disease in children but for women in the early stages of pregnancy, it can cause spontaneous abortion, congenital rubella syndrome (CRS) and associated birth defects. Despite the availability of an effective vaccine, rubella virus continues to circulate endemically in several regions of the world. This is particularly true in East and Southeast (E/SE) Asia, where control efforts vary widely among countries that are well connected through travel and immigration. It is therefore important to understand how the regional persistence of rubella is affected both by dynamics occurring across countries and susceptibility within countries. Here, we use genetic and epidemiological data from countries in E/SE Asia to explore the phylogeography of rubella virus in this region. Our results underline that metapopulation dynamics are key for rubella persistence and highlight the source-sink population structure of the region. We identify countries that contribute to the regional metapopulation network and link epidemic dynamics to susceptibility profiles within each country. Our results indicate that human movement plays an important role in driving epidemic dynamics in E/SE Asia

Transgenic Parasites Stably Expressing Full-Length \u3ci\u3ePlasmodium falciparum\u3c/i\u3e Circumsporozoite Protein as a Model for Vaccine Down- Selection in Mice Using Sterile Protection as an Endpoint

Circumsporozoite protein (CSP) of Plasmodium falciparum is a protective human malaria vaccine candidate. There is an urgent need for models that can rapidly down-select novel CSP-based vaccine candidates. In the present study, the mouse-mosquito transmission cycle of a transgenic Plasmodium berghei malaria parasite stably expressing a functional full-length P. falciparum CSP was optimized to consistently produce infective sporozoites for protection studies. A minimal sporozoite challenge dose was established, and protection was defined as the absence of blood-stage parasites 14 days after intravenous challenge. The specificity of protection was confirmed by vaccinating mice with multiple CSP constructs of differing lengths and compositions. Constructs that induced high NANP repeat-specific antibody titers in enzyme-linked immunosorbent assays were protective, and the degree of protection was dependent on the antigen dose. There was a positive correlation between antibody avidity and protection. The antibodies in the protected mice recognized the native CSP on the parasites and showed sporozoite invasion inhibitory activity. Passive transfer of anti-CSP antibodies into naive mice also induced protection. Thus, we have demonstrated the utility of a mouse efficacy model to down-select human CSP-based vaccine formulations

Small genome of the fungus Escovopsis weberi, a specialized disease agent of ant agriculture

Many microorganisms with specialized lifestyles have reduced genomes. This is best understood in beneficial bacterial symbioses, where partner fidelity facilitates loss of genes necessary for living independently. Specialized microbial pathogens may also exhibit gene loss relative to generalists. Here, we demonstrate that Escovopsis weberi, a fungal parasite of the crops of fungus-growing ants, has a reduced genome in terms of both size and gene content relative to closely related but less specialized fungi. Although primary metabolism genes have been retained, the E. weberi genome is depleted in carbohydrate active enzymes, which is consistent with reliance on a host with these functions. E. weberi has also lost genes considered necessary for sexual reproduction. Contrasting these losses, the genome encodes unique secondary metabolite biosynthesis clusters, some of which include genes that exhibit up-regulated expression during host attack. Thus, the specialized nature of the interaction between Escovopsis and ant agriculture is reflected in the parasite's genome