C-reactive protein mediates the effect of apolipoprotein E on cytomegalovirus infection

Background. Although the apolipoprotein (APOE)-epsilon 4 allele has been shown to determine the outcome of several infections, its relationship with cytomegalovirus (CMV) has not been explored. We examine whether APOE determines CMV and herpes simplex virus type 1 (HSV-1) antibody levels and assess whether C-reactive protein (CRP) mediates any observed relationships. Methods. We conducted a cross-sectional analysis of a randomly selected subset (n = 1561/1789) of participants aged 60-101 in the Sacramento Area Latino Study on Aging. Blood samples were tested for APOE genotype, CRP, and immunoglobulin G antibodies to CMV and HSV-1. Multivariate logistic regression was used to examine the association between epsilon 4 and CMV and HSV antibody levels. We also assessed whether CRP mediates the effects of any observed associations between epsilon 4 and viral antibody levels. Results. CMVantibody and CRP levels varied significantly by APOE genotype. The association between CRP and CMV antibody was strengthened in the presence of epsilon 4. In contrast, this effect was not observed in HSV-1. We found that APOE-epsilon 4 carriers had significantly lower levels of CRP yet significantly higher levels of CMV antibodies, suggesting a mediating pathway. Conclusions. APOE-epsilon 4 carriers may experience immunological aberrations that lead to lower levels of CRP and correspondingly higher CMV antibody levels.