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Title: The influence of host genetics on Marek's disease virus evolution

item Hunt, Henry
item Dunn, John

Submitted to: Avian Diseases
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 12/28/2012
Publication Date: 1/15/2013
Citation: Hunt, H.D., Dunn, J.R. 2013. The influence of host genetics on Marek's disease virus evolution. Avian Diseases. 57(2):474-482.

Interpretive Summary: Marek’s disease is a cancer-like disease of chickens induced by the Marek’s disease virus (MDV). Over the past 50 years MDV has become more virulent requiring poultry producers to employ more potent vaccines and select for more resistant genetic stocks to control the disease. The nature of this increased virulence is not well understood and the effects of poultry genetics on virus evolution are unknown. This report assesses the importance of genetic resistance on MDV evolution and will undoubtedly help poultry breeders in their selection process.

Technical Abstract: Since the first report of a polyneuritis in chickens by Joseph Marek in 1907 (24), the clinical nature of the disease has changed. Over the last five decades, the pathogenicity of the Marek's disease virus (MDV) has continued to evolve from the relatively mild strains (mMDV) observed in the 1960s to the more severe strains labeled very virulent plus (vv+MDV) currently observed in today's outbreaks. To understand the influence of host genetics, specifically the major histocompatibility complex (MHC), on virus evolution a bacterial artificial chromosome derived MDV (Md5B40BAC) was passed in vivo (IVP) through resistant (MHC-B21) and susceptible (MHC-B13) "semi-congenic" Line 0 chickens. Criteria for selecting virus isolates for in vivo passage were based on virus replication in white blood cells (WBCs) 21 days after challenge and evaluation of MD pathology at necropsy. In the MHC-B13 susceptible line the Md5B40BAC virulence consistently increased from 18% Marek's disease (MD) after in vivo passage one (B13-IVP1 Md5B40BAC) to 94% MD after B13-IVP5 Md5B40BAC challenge. In the MHC-B21 resistant line Marek's disease virulence fluctuated from 28% at B21-IVP1 Md5B40BAC to a high of 65% in B21-IVP2 Md5B40BAC back to a low of 23% in B21-IVP5 Md5B40BAC challenged chicks. Although the B21-IVP5 Md5B40BAC isolates were relatively mild in the MHC-B21 chicken line (56% MDV) they were highly virulent in the MHC-B13 line (100% MDV respectively). From this series of experiments it would appear that MDV evolution toward greater virulence occurs in both susceptible and resistant MHC haplotypes but the resulting increase in pathogenicity is constrained by the resistant MHC haplotype.