Abstract
The innate immune response provides a first line of defense against pathogens by targeting generic differential features that are present in foreign organisms but not in the host. These innate responses generate selection forces acting both in pathogens and hosts that further determine their co-evolution. Here we analyze the nucleic acid sequence fingerprints of these selection forces acting in parallel on both host innate immune genes and ssRNA viral genomes. We do this by identifying dinucleotide biases in the coding regions of innate immune response genes in plasmacytoid dendritic cells, and then use this signal to identify other significant host innate immune genes. The persistence of these biases in the orthologous groups of genes in humans and chickens is also examined. We then compare the significant motifs in highly expressed genes of the innate immune system to those in ssRNA viruses and study the evolution of these motifs in the H1N1 influenza genome. We argue that the significant under-represented motif pattern of CpG in an AU context - which is found in both the ssRNA viruses and innate genes, and has decreased throughout the history of H1N1 influenza replication in humans - is immunostimulatory and has been selected against during the co-evolution of viruses and host innate immune genes. This shows how differences in host immune biology can drive the evolution of viruses that jump into species with different immune priorities than the original host.
Highlights
The innate immune system encompasses the non-specific response of an organism to broad classes of foreign pathogens [1]
As a first step we compare the CpG profiles from mouse and human genes to determine if they are similar enough to warrant the use of mouse plasmacytoid dendritic cells (pDCs) expression data as the basis of this study
It is clear that there are shared di, tetra, and hexanucleotide sequence biases between ssRNA viruses and the mRNAs of host innate immune genes. These common evolutionary pressures could be due to common mutational processes or common selection forces
Summary
The innate immune system encompasses the non-specific response of an organism to broad classes of foreign pathogens [1]. The ability of a pathogen to avoid or trigger recognition by the innate immune system will likely affect its survival. In the evolution of RNA viruses, for instance, where the genetic mutation rate is orders of magnitude higher than in the host’s genome, one would expect that a virus’s evolutionary history strongly reflects its exposure to host recognition receptors. One should be able to use an RNA virus replication time series to identify possible triggers of non-self material. If many different RNA viruses coinfecting the same host species have avoided certain sequence motifs for reasons that are not functional or structural, one may hypothesize that these patterns are PAMPs that the virus has evolved to avoid
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