Models of contrasting strategies of rhinovirus immune manipulation

Abstract

Rhinoviruses, consisting of well over one hundred serotypes that cause a plurality of common colds, are completely cleared by the host immune system after causing minimal cell death, but often without inducing long-term immune memory. We develop mathematical models of two kinds of rhinoviruses, the major group and minor group, that use different receptors to enter target cells. Roughly the 90 serotypes in the major group bind to ICAM-1, a molecule that is upregulated on antigen-presenting cells, and alter the timing, location and type of the immune response. The 12 members of the minor group do not so modulate the response. Our model predicts similar virus dynamics for the major and minor groups but with quite different underlying mechanisms. Over a range of key parameters that quantify immune manipulation, disease outcomes lie within a triangle in the plane describing damage and memory, of which the major and minor group form two corners. This model of infection by a highly adapted and low virulence virus provides a starting point for understanding the development of asthma and other pathologies.