On the dynamics of acute EBV infection and the pathogenesis of infectious mononucleosis
Department of Pediatrics; Program in Molecular Medicine
Acute Disease; Cell Proliferation; Cytotoxicity, Immunologic; Herpesvirus 4, Human; Immunologic Memory; Infectious Mononucleosis; Time Factors
Immunology and Infectious Disease | Pediatrics
Memory B cells latently infected with Epstein-Barr virus (mB(Lats)) in the blood disappear rapidly on presentation with acute symptomatic primary infection (acute infectious mononucleosis [AIM]). They undergo a simple exponential decay (average half-life: 7.5 +/- 3.7 days) similar to that of normal memory B cells. The cytotoxic T lymphocyte (CTL) response to immediate early (IE) lytic antigens (CTL(IEs)) also decays over this time period, but no such correlation was observed for the CTL response to lytic or latent antigens or to the levels of virions shed into saliva. We have estimated the average half-life of CTL(IEs) to be 73 (+/- 23) days. We propose that cycles of infection and reactivation occur in the initial stages of infection that produce high levels of mB(Lats) in the circulation. Eventually the immune response arises and minimizes these cycles leaving the high levels of mB(Lats) in the blood to decay through simple memory B-cell homeostasis mechanisms. This triggers the cells to reactivate the virus whereupon most are killed by CTL(IEs) before they can release virus and infect new cells. The release of antigens caused by this large-scale destruction of infected cells may trigger the symptoms of AIM and be a cofactor in other AIM-associated diseases.
DOI of Published Version
Blood. 2008 Feb 1;111(3):1420-7. Epub 2007 Nov 8. Link to article on publisher's site
Hadinoto, Vey; Shapiro, Michael; Greenough, Thomas C.; Sullivan, John L.; Luzuriaga, Katherine; and Thorley-Lawson, David A., "On the dynamics of acute EBV infection and the pathogenesis of infectious mononucleosis" (2008). Immunology/Infectious Disease. 60.