Host Specialisation, Immune Cross-Reaction and the Composition of Communities of Co-circulating Borrelia Strains

We use mathematical modelling to examine how microbial strain communities are structured by the host specialisation traits and antigenic relationships of their members. The model is quite general and broadly applicable, but we focus on Borrelia burgdorferi, the Lyme disease bacterium, transmitted by ticks to mice and birds. In this system, host specialisation driven by the evasion of innate immunity has been linked to multiple niche polymorphism, while antigenic differentiation driven by the evasion of adaptive immunity has been linked to negative frequency dependence. Our model is composed of two host species, one vector, and multiple co-circulating pathogen strains that vary in their host specificity and their antigenic distances from one another. We explore the conditions required to maintain pathogen diversity. We show that the combination of host specificity and antigenic differentiation creates an intricate niche structure. Unequivocal rules that relate the stability of a strain community directly to the trait composition of its members are elusive. However, broad patterns are evident. When antigenic differentiation is weak, stable communities are typically composed entirely of generalists that can exploit either host species equally well. As antigenic differentiation increases, more diverse stable communities emerge, typically around trait compositions of generalists, generalists and very similar specialists, and specialists roughly balanced between the two host species.

Genetic, Morphological and Antigenic Relationships between Mesonivirus Isolates from Australian Mosquitoes and Evidence for Their Horizontal Transmission

The Mesoniviridae are a newly assigned family of viruses in the order Nidovirales. Unlike other nidoviruses, which include the Coronaviridae, mesoniviruses are restricted to mosquito hosts and do not infect vertebrate cells. To date there is little information on the morphological and antigenic characteristics of this new group of viruses and a dearth of mesonivirus-specific research tools. In this study we determined the genetic relationships of recent Australian isolates of Alphamesonivirus 4 (Casuarina virus—CASV) and Alphamesonivirus 1 (Nam Dinh virus—NDiV), obtained from multiple mosquito species. Australian isolates of NDiV showed high-level similarity to the prototype NDiV isolate from Vietnam (99% nucleotide (nt) and amino acid (aa) identity). Isolates of CASV from Central Queensland were genetically very similar to the prototype virus from Darwin (95–96% nt and 91–92% aa identity). Electron microscopy studies demonstrated that virion diameter (≈80 nm) and spike length (≈10 nm) were similar for both viruses. Monoclonal antibodies specific to CASV and NDiV revealed a close antigenic relationship between the two viruses with 13/34 mAbs recognising both viruses. We also detected NDiV RNA on honey-soaked nucleic acid preservation cards fed on by wild mosquitoes supporting a possible mechanism of horizontal transmission between insects in nature.

Selective Reactivity of Anti-Japanese Encephalitis Virus NS4B Antibody Towards Different Flaviviruses

Studies investigating West Nile virus (WNV) NS4B protein function are hindered by the lack of an antibody recognizing WNV NS4B protein. Few laboratories have produced WNV NS4B antibodies, and none have been shown to work consistently. In this report, we describe a NS4B antibody against Japanese encephalitis virus (JEV) NS4B protein that cross-reacts with the NS4B protein of WNV but not of dengue virus (DENV). This JEV NS4B antibody not only recognizes WNV NS4B in infected cells, but also recognizes the NS4B protein expressed using transfection. It is evident from this data that the JEV NS4B antibody is specific to NS4B of WNV but not to NS4B of the four DENV serotypes. The specificity of this antibody may be due to the notable differences that exist between the amino acid sequence identity and antigenic relationships within the NS4B protein of the WNV, DENV, and JEV.

Dengue genetic divergence generates within-serotype antigenic variation, but serotypes dominate evolutionary dynamics

Dengue virus (DENV) exists as four genetically distinct serotypes, each of which is historically assumed to be antigenically uniform. Recent analyses suggest that antigenic heterogeneity may exist within each serotype, but its source, extent and impact remain unclear. Here, we construct a sequence-based model to directly map antigenic change to underlying genetic divergence. We identify 49 specific substitutions and four colinear substitution clusters that robustly predict dengue antigenic relationships. We report moderate antigenic diversity within each serotype, resulting in genotype-specific patterns of heterotypic cross-neutralization. We also quantify the impact of antigenic variation on real-world DENV population dynamics, and find that serotype-level antigenic fitness is a dominant driver of dengue clade turnover. These results provide a more nuanced understanding of the relationship between dengue genetic and antigenic evolution, and quantify the effect of antigenic fitness on dengue evolutionary dynamics.