Fig. 4. Age-dependent outcomes in herpesvirus immunomodulation.

(A). Herpesvirus latency as a mutualistic symbiosis to promote cross protection from secondary infection. This hypothesis postulates that all organisms are born with a basal level of innate resistance to infection. Specific pathogen-free mice represent this basal level. As humans acquire multiple herpesviruses during their early years of life, latency-driven immune responses trigger increased resistance to secondary infections. This cross protection may be transient or durable as described in the text. (B). If herpesviruses are acquired during early life, beneficial immune modulation including cross protection from infections and immune skewing away from Th2-driven allergic inflammation may result. In contrast, following herpesvirus infection later in life, latency-driven inflammation may exacerbate host inflammatory diseases. If infections are acquired predominantly in late childhood through adulthood, this model predicts that the primary outcomes for the host will be pathologic.