Human antibody reactivity against the lower matrix protein (pp65) produced by cytomegalovirus

The lower matrix protein (pp65) is a major product of many laboratory strains of cytomegalovirus (CMV). It is thus an integral part of many CMV serological assays based on native antigen. Recombinant fragments of pp65 have previously been investigated for their usefulness in more-defined assays. The latter antigens have, however, failed to develop a positive response with serum samples derived from a substantial number of infected individuals. Here we show that the human humoral immune response to CMV pp65 is highly diverse and recognizes at least seven distinct but in some cases partly overlapping epitopes. Most of these epitopes could not be mimicked by any of the investigated recombinant or synthetic antigens. Furthermore, when we investigated the ability of human CMV-seropositive serum samples to block the reactivity of pp65-specific antibodies recognizing five different epitopes within pp65, it was evident that several sera did not contain significant levels of antibodies against any of these or overlapping structures. It was thus concluded that the antibody response against CMV pp65 is weak in some CMV-infected individuals, making this antigen unsuitable for use alone in serological screening systems for CMV infection.