Possibly more importantly, Zhou and Deems [54] have argued that, in dengue (for which there are four known viral subtypes), OAS is augmented when infection with a highly antigenic subtype is followed by infection with a cross-reactive subtype that is significantly sub-dominant to the first, and is muted in the reverse situation (first infection by a sub-dominant subtype followed by second infection with a more dominant subtype). This evidence concerns the gene SMOC1 and dengue disease.