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Proc Natl Acad Sci U S A. 1987 Jan; 84(2): 570–574.
PMCID: PMC304252

Antibody responses to Epstein-Barr virus-determined nuclear antigen (EBNA)-1 and EBNA-2 in acute and chronic Epstein-Barr virus infection.


Five distinct Epstein-Barr virus (EBV)-determined nuclear antigens (EBNA-1 to EBNA-5) were recently identified. Antibody responses to these antigens could conceivably differ, and thus prove of serodiagnostic value, in EBV-associated disease processes. As a first step, murine or human cell lines transfected with appropriate EBV DNA fragments and stably expressing either EBNA-1 or EBNA-2 were used to determine the frequency and time of emergence of antibodies to these two antigens in the course of acute and chronic infectious mononucleosis (IM) and to assess their titers in so-called chronic active EBV infections. Following IM, antibodies to EBNA-2 arose first and, after reaching peak titers, declined again in time to lower persistent or even nondetectable levels. Antibodies to EBNA-1 emerged several weeks or months after anti-EBNA-2 and gradually attained the titers at which they persisted indefinitely. The ratios between the anti-EBNA-1 and anti-EBNA-2 titers therefore were generally well below 1.0 during the first 6-12 months after IM and turned to well above 1.0 during the second year. In clear cases of chronic IM, the inversion of this ratio was delayed or prevented. In the less well-defined chronic EBV infections, low ratios were observed in only some of the patients. Because many of these illnesses were not ushered in by a proven IM and often showed EBV-specific antibody profiles within the normally expected range, a causal role of the virus in these cases remains doubtful.

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  • Henie G, Henle W, Horwitz CA. Antibodies to Epstein-Barr virus-associated nuclear antigen in infectious mononucleosis. J Infect Dis. 1974 Sep;130(3):231–239. [PubMed]
  • Henle W, Henle G. Epstein-Barr virus-specific serology in immunologically compromised individuals. Cancer Res. 1981 Nov;41(11 Pt 1):4222–4225. [PubMed]
  • Strnad BC, Schuster TC, Hopkins RF, 3rd, Neubauer RH, Rabin H. Identification of an Epstein-Barr virus nuclear antigen by fluoroimmunoelectrophoresis and radioimmunoelectrophoresis. J Virol. 1981 Jun;38(3):996–1004. [PMC free article] [PubMed]
  • Summers WP, Grogan EA, Shedd D, Robert M, Liu CR, Miller G. Stable expression in mouse cells of nuclear neoantigen after transfer of a 3.4-megadalton cloned fragment of Epstein-Barr virus DNA. Proc Natl Acad Sci U S A. 1982 Sep;79(18):5688–5692. [PMC free article] [PubMed]
  • Hennessy K, Kieff E. One of two Epstein-Barr virus nuclear antigens contains a glycine-alanine copolymer domain. Proc Natl Acad Sci U S A. 1983 Sep;80(18):5665–5669. [PMC free article] [PubMed]
  • Dillner J, Kallin B, Ehlin-Henriksson B, Timar L, Klein G. Characterization of a second Epstein-Barr virus-determined nuclear antigen associated with the BamHI WYH region of EBV DNA. Int J Cancer. 1985 Mar 15;35(3):359–366. [PubMed]
  • Rymo L, Klein G, Ricksten A. Expression of a second Epstein-Barr virus-determined nuclear antigen in mouse cells after gene transfer with a cloned fragment of the viral genome. Proc Natl Acad Sci U S A. 1985 May;82(10):3435–3439. [PMC free article] [PubMed]
  • Hennessy K, Fennewald S, Kieff E. A third viral nuclear protein in lymphoblasts immortalized by Epstein-Barr virus. Proc Natl Acad Sci U S A. 1985 Sep;82(17):5944–5948. [PMC free article] [PubMed]
  • Dillner J, Kallin B, Ehlin-Henriksson B, Rymo L, Henle W, Henle G, Klein G. The Epstein-Barr virus determined nuclear antigen is composed of at least three different antigens. Int J Cancer. 1986 Feb 15;37(2):195–200. [PubMed]
  • Kallin B, Dillner J, Ernberg I, Ehlin-Henriksson B, Rosén A, Henle W, Henle G, Klein G. Four virally determined nuclear antigens are expressed in Epstein-Barr virus-transformed cells. Proc Natl Acad Sci U S A. 1986 Mar;83(5):1499–1503. [PMC free article] [PubMed]
  • Dillner J, Kallin B, Alexander H, Ernberg I, Uno M, Ono Y, Klein G, Lerner RA. An Epstein-Barr virus (EBV)-determined nuclear antigen (EBNA5) partly encoded by the transformation-associated Bam WYH region of EBV DNA: preferential expression in lymphoblastoid cell lines. Proc Natl Acad Sci U S A. 1986 Sep;83(17):6641–6645. [PMC free article] [PubMed]
  • Yates J, Warren N, Reisman D, Sugden B. A cis-acting element from the Epstein-Barr viral genome that permits stable replication of recombinant plasmids in latently infected cells. Proc Natl Acad Sci U S A. 1984 Jun;81(12):3806–3810. [PMC free article] [PubMed]
  • Menezes J, Leibold W, Klein G. Biological differences between Epstein-Barr virus (EBV) strains with regard to lymphocyte transforming ability, superinfection and antigen induction. Exp Cell Res. 1975 May;92(2):478–484. [PubMed]
  • Dillner J, Sternås L, Kallin B, Alexander H, Ehlin-Henriksson B, Jörnvall H, Klein G, Lerner R. Antibodies against a synthetic peptide identify the Epstein-Barr virus-determined nuclear antigen. Proc Natl Acad Sci U S A. 1984 Aug;81(15):4652–4656. [PMC free article] [PubMed]
  • Mueller-Lantzsch N, Lenoir GM, Sauter M, Takaki K, Béchet JM, Kuklik-Roos C, Wunderlich D, Bornkamm GW. Identification of the coding region for a second Epstein-Barr virus nuclear antigen (EBNA 2) by transfection of cloned DNA fragments. EMBO J. 1985 Jul;4(7):1805–1811. [PMC free article] [PubMed]
  • Hennessy K, Kieff E. A second nuclear protein is encoded by Epstein-Barr virus in latent infection. Science. 1985 Mar 8;227(4691):1238–1240. [PubMed]
  • Dillner J, Kallin B, Klein G, Jörnvall H, Alexander H, Lerner R. Antibodies against synthetic peptides react with the second Epstein-Barr virus-associated nuclear antigen. EMBO J. 1985 Jul;4(7):1813–1818. [PMC free article] [PubMed]
  • Marklund G, Henle W, Henle G, Ernberg I. IgA antibodies to Epstein-Barr virus in infectious mononucleosis. Scand J Infect Dis. 1986;18(2):111–119. [PubMed]
  • Horwitz CA, Henle W, Henle G, Rudnick H, Latts E. Long-term serological follow-up of patients for Epstein-Barr virus after recovery from infectious mononucleosis. J Infect Dis. 1985 Jun;151(6):1150–1153. [PubMed]
  • Andersson J, Britton S, Ernberg I, Andersson U, Henle W, Sköldenberg B, Tisell A. Effect of acyclovir on infectious mononucleosis: a double-blind, placebo-controlled study. J Infect Dis. 1986 Feb;153(2):283–290. [PubMed]
  • Marklund G, Ernberg I, Lundberg C, Henle W, Henle G. Differences in EBV-specific antibody patterns at onset of infectious mononucleosis. Scand J Infect Dis. 1986;18(1):25–32. [PubMed]
  • Straus SE, Tosato G, Armstrong G, Lawley T, Preble OT, Henle W, Davey R, Pearson G, Epstein J, Brus I, et al. Persisting illness and fatigue in adults with evidence of Epstein-Barr virus infection. Ann Intern Med. 1985 Jan;102(1):7–16. [PubMed]
  • Edson CM, Cohen LK, Henle W, Strominger JL. An unusually high-titer human anti-Epstein Barr virus (EBV) serum and its use in the study of EBV-specific proteins synthesized in vitro and in vivo. J Immunol. 1983 Feb;130(2):919–924. [PubMed]
  • Schooley RT, Carey RW, Miller G, Henle W, Eastman R, Mark EJ, Kenyon K, Wheeler EO, Rubin RH. Chronic Epstein-Barr virus infection associated with fever and interstitial pneumonitis. Clinical and serologic features and response to antiviral chemotherapy. Ann Intern Med. 1986 May;104(5):636–643. [PubMed]
  • Henle W, Henle GE, Horwitz CA. Epstein-Barr virus specific diagnostic tests in infectious mononucleosis. Hum Pathol. 1974 Sep;5(5):551–565. [PubMed]
  • Reedman BM, Klein G. Cellular localization of an Epstein-Barr virus (EBV)-associated complement-fixing antigen in producer and non-producer lymphoblastoid cell lines. Int J Cancer. 1973 May;11(3):499–520. [PubMed]
  • Miller G, Grogan E, Fischer DK, Niederman JC, Schooley RT, Henle W, Lenoir G, Liu CR. Antibody responses to two Epstein-Barr virus nuclear antigens defined by gene transfer. N Engl J Med. 1985 Mar 21;312(12):750–755. [PubMed]
  • Niederman JC, Miller G. Kinetics of the antibody response to BamHI-K nuclear antigen in uncomplicated infectious mononucleosis. J Infect Dis. 1986 Aug;154(2):346–349. [PubMed]
  • DuBois RE, Seeley JK, Brus I, Sakamoto K, Ballow M, Harada S, Bechtold TA, Pearson G, Purtilo DT. Chronic mononucleosis syndrome. South Med J. 1984 Nov;77(11):1376–1382. [PubMed]
  • Jones JF, Ray CG, Minnich LL, Hicks MJ, Kibler R, Lucas DO. Evidence for active Epstein-Barr virus infection in patients with persistent, unexplained illnesses: elevated anti-early antigen antibodies. Ann Intern Med. 1985 Jan;102(1):1–7. [PubMed]
  • Masucci G, Mellstedt H, Masucci MG, Szigeti R, Ernberg I, Björkholm M, Tsukuda K, Henle G, Henle W, Pearson G, et al. Immunological characterization of Hodgkin's and non-Hodgkin's lymphoma patients with high antibody titers against Epstein-Barr virus-associated antigens. Cancer Res. 1984 Mar;44(3):1288–1300. [PubMed]
  • Sixbey JW, Nedrud JG, Raab-Traub N, Hanes RA, Pagano JS. Epstein-Barr virus replication in oropharyngeal epithelial cells. N Engl J Med. 1984 May 10;310(19):1225–1230. [PubMed]

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