Subversion of innate and adaptive immunity: Immune evasion from antibody and complement

Many herpesviruses encode immune evasion molecules that interfere with activities mediated by antibody and complement, suggesting the importance of antibody and complement in host defense against herpes infections. How does this observation reconcile with the clinical findings that severe infections develop mostly in subjects with T-cell deficiencies, such as transplant recipients or those with advanced HIV infection? An explanation that we favor is that T-cells assume a pivotal role in host defense partly because herpesviruses are very effective at limiting the activities of antibody and complement. Support for this hypothesis comes from experimental studies using mutant HSV-1 strains defective in antibody and complement immune evasion that demonstrate a marked increased in effectiveness of antibody and complement in host defense against the mutant viruses (Lubinski et al., 2002). Newborns lack mature T-cell repertoires and generally have low serum complement levels; therefore, observations in human newborns provide opportunities to assess the contributions of antibodies independent of T-cells and perhaps complement in host defense against herpesviruses. The severity of HSV and CMV infection in the fetus and newborn are greatly reduced when the infection in the mother is recurrent rather than primary. In recurrent infection, antibodies pass transplacentally to the fetus and protect against the infection. Passive transfer of VZV antibodies from mother to fetus protects the newborn from severe chickenpox when exposed days to weeks after delivery.