Submitted to: Virology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 9/6/2006
Publication Date: 3/1/2007
Citation: Niikura, M., Kim, T., Hunt, H.D., Burnside, J., Morgan, R., Dodgson, J., Cheng, H.H. 2007. Marek's disease virus up-regulates major histocompatibility complex class II cell surface expression in infected cells. Virology. 359(1): 212-219. Interpretive Summary: Marek’s disease (MD) is an economically-important disease of chickens caused by a pathogenic virus known as the Marek’s disease virus (MDV). Currently, vaccines have controlled the problem but new emerging viral strains that vaccines cannot control are being encountered more frequently. Thus, understanding the biology of how MDV induces tumors in susceptible chickens is critical for long-term control. In this paper, we show that MDV is unique among all herpesviruses in that it up-regulates MHC class II, a key component of the immune system, on the surface of infected cells. As MDV is a highly cell-associated virus, this result suggests MDV tricks the immune system to allow cell-to-cell spread of virions to other immune cells. This information enhances our understanding of MDV pathogenicity and suggests possibilities for improved control of MD.
Technical Abstract: Many herpesviruses modulate major histocompatibility complex (MHC) expression on the cell surface as an immune evasion mechanism. We report here that Marek's disease virus (MDV), a lymphotrophic avian alphaherpesvirus, up-regulates MHC class II cell surface expression in infected cells, contrary to all other herpesviruses examined to date. This MDV-induced class II up-regulation was detected both in vitro and in vivo. The up-regulation was not solely an indirect effect of interferon, which is a highly potent natural inducer of MHC class II expression, since MHC class II up-regulation in cultured primary fibroblast cells was confined to the infected cells only. MHC class II up-regulation was also observed in infected cells of the bursa of Fabricius during the lytic phase of MDV infection in birds and upon reactivation of MDV from latency in an MDV-transformed cell line. As MDV is a strictly cell-associated virus and requires activated T cells for its life cycle, this up-regulation of MHC class II in infected cells may contribute to virus spread within the infected host by increasing the chance of contact between productively infected cells and susceptible activated T cells.