Humoral immune response to proteins of human cytomegalovirus latency-associated transcripts

Latent human cytomegalovirus (CMV) infection of hematopoietic progenitor ce lls is associated with the presence of latency-associated transcripts that may express 6 proteins larger than 44 amino acids in size (open reading fra me [ORF] 55, ORF45, ORF94, ORF59, ORF154, ORF152/UL124). The serologic resp onse to these proteins was evaluated in healthy seropositive individuals as well as in individuals undergoing active CMV infection. Individual recombi nant GST-fusion proteins, prepared from bacteria, were found by enzyme-link ed immunosorbent assay to be recognized by between 8% and 44% long-term hea lthy seropositive individuals, with ORF94 and ORF55 being the most broadly and significantly recognized. Although nearly all of serum samples (85%) re cognized at least 1 of these proteins, none reacted with all 6. Patterns of antibody prevalence to these proteins in long-term seropositive individual s were similar to many antigens expressed during productive replication (IE 1, ppUL57, ppUL83/pp65), but none were broadly detected by a majority of in dividuals, a characteristic of only a few productive-phase antigens, includ ing ppUL44/ICP36 and ppUL32/pp150. Consistent with prevalence in long-term seropositive individuals, commercial preparations of pooled human gamma glo bulin were also found to recognize latency-associated proteins. Serologic r eactivity to latency-associated proteins was slow to develop following prim ary infection, in a pattern distinct from any of the characterized replicat ion-phase proteins tested here, and was boosted late after secondary infect ion or reactivation in solid-organ transplant recipients without showing a correlation with viremia or disease. These results provide evidence that pr oteins expressed from the latent region during natural infection exhibit im munogenicity comparable with most other characterized viral antigens, altho ugh the narrow response to individual latency-associated proteins likely pr ecludes their use in serologic assays to investigate clinical correlates or outcome in transplant recipients.