Primary and recurrent cytomegalovirus infections have different effects on human herpesvirus-6 antibodies in immunosuppressed organ graft recipients: absence of virus cross-reactivity and evidence for virus interaction.

Abstract

The relationship between serum antibodies to human herpesvirus-6 (HHV-6) and cytomegalovirus (CMV) infection was studied in immunosuppressed adult organ graft recipients all of whom had IgG to both HHV-6 and Epstein-Barr virus capsid antigen (EBVCA) before operation and who had received an organ or organs from HHV-6 seropositive donors. In primary CMV infection the titre of IgG to HHV-6 rose substantially (between 32- and 512-fold) in eight out of eight patients whereas IgG to EBVCA only rose 32-fold in two patients. Moreover, the HHV-6 responses coincided closely with the CMV seroconversion. Serum absorption studies gave no evidence for antibody cross-reaction between CMV and HHV-6 because the CMV antibody titre could be reduced specifically without affecting HHV-6 antibody titres and vice versa. In recurrent CMV infection, HHV-6 antibody levels rose (32-fold) in three out of eight patients but these changes did not coincide with the CMV antibody response. Similarly, in the complete absence of CMV infection, five out of eight patients showed antibody rises to HHV-6 (between four- and 16-fold). IgG titres to EBVCA were stable in both these groups of patients. It is concluded that there is serological evidence (rising titre greater than or equal to four-fold) for genuine HHV-6 reactivation or, alternatively, for reinfection in 16 out of the 24 patients. This phenomenon was most frequent in primary CMV infection where the largest HHV-6 antibody responses were seen probably because of an, as yet, undetermined interaction between the two viruses.