One important practical consequence of the involvement of many distinct rare variants in host defense is that it likely will be necessary to completely sequence candidate susceptibility genes in large samples of affected individuals and control subjects to identify disease association.
The breadth of the WNV CP40 mutant swarm was shown to be directly correlated with virus adaptation, and reverse genetics studies demonstrated that consensus mutations were not solely responsible for the adaptive phenotype, indicating the importance of mutant swarm variants in host adaptation and overall viral fitness [ 19, 22].
These autologous neutralization data suggest that the "late" SHIV-1157ipd3N4 arose as a neutralization escape variant in host RPn-8 by selective pressure exerted by high-level nAbs.
In order to further investigate the role of each PilC variant in host cell motility independently from possible artefacts caused by IPTG induction, we used time-lapse microscopy to monitor PilC1- or PilC2-mediated adhesion of the meningococcal isogenic Nm604a and Nm910f strains to ME180 cells.
It becomes clear that searching for evidence of selective pressures on genes involved in immunity-related processes or host pathogen interactions represents a complementary strategy for identifying functionally important genes and variants involved in host immunity to infection and disease outcome (Olson 2002; Bamshad and Wooding 2003; Bradbury 2004).
This effect appears to be a particular impediment to optimizing vaccination strategies for reducing the transmission and adaptation rates of new variants in the host population.
In our model, a single parameter summarizes the within-host dynamics: the mutation-selection balance between nonadapted and resistance-breaking pathogen variants in S hosts.
For HIV-1, GWAS demonstrate that some naturally selected variants in the host-pathogen protein interaction networks continue to have functional consequences for susceptibility to these pathogens.
In particular, to recover differences in patterns of infection among hosts, the rank order of the parasite variants' baseline multiplication factors differed between hosts (i.e. the fastest growing variant in one host was not the fastest growing in all hosts, Molineaux et al., 2001).
However, as the diversity and order of PfEMP1 variants in the human host is influenced by immune responses and other host factors (Kyriacou et al., 2006; Warimwe et al., 2009), attempts to elucidate the underlying patterns of antigenic change and estimate related switching parameters are commonly based on in vitro cultured parasites in the absence of selection pressure.
There are many technical challenges to increasing cellulose-specific performance, including development of representative and predictive screens, expression of variants in an appropriate host, measurement of specific activity which includes high-throughput specific protein determination, and the ability to query cellulase activity in a background of confounding activities.
