A synthetic peptide for detecting antibodies to Epstein-Barr virus nuclear antigen in sera from patients with infectious mononucleosis

When humans are infected with Epstein-Barr virus (EBV), the causative agent of infectious mononucleosis (IM), a variety of antibody responses develop against several viral encoded proteins. These viral antigens include viral capsid antigen (VCA), two distinct early antigens, and the Epstein-Barr Virus nuclear antigen (EBNA) [1]. Infectious mononucleosis may be diagnosed serologically with the heterophil test, but it has been shown that MO^o of adult patients do not have a heterophil response [2-5]; this percentage may be higher in children [6]. Recently, Hennessy and Kieff [7, 8] have identified the segment of EBV DNA that contained the nucleotide sequence specifying the EBNA protein. They described a repeating DNA region (IR-3) that contained only glycine and alanine residues [7]. Synthetic peptides representing this region were synthesized; one peptide, P62, was shown to be highly specific in detecting human antibodies to EBV [9, 10]. We have used the ELISA with peptide P62 to examine the antibody response to the EBNA-specific peptide in several panels of well-defined sequential sera from patients with IM. We found that all patients, whether or not they were heterophil-positive, had an early IgM response to the P62 peptide, whereas the IgG response was usually delayed for several months or more. Thus, a high ratio of IgM-to-IgG antibody to P62 was characteristic of primary EBV infection. We also found IgA antibody to P62 in 10 of 13 patients with IM.