|HEARN, CARI - Michigan State University|
|PREEYANON, LIKIT - Michigan State University|
|YORK, IAN - Centers For Disease Control And Prevention (CDC) - United States|
Submitted to: Virology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 11/4/2014
Publication Date: 11/27/2014
Publication URL: http://handle.nal.usda.gov/10113/60128
Citation: Hearn, C., Preeyanon, L., Hunt, H.D., York, I.A. 2014. AN MHC class I immune evasion gene of Marek's disease virus. Virology. 475:88-95. doi:10.1016/j.virol.2014.11.008.
Interpretive Summary: The herpesvirus Marek’s Disease Virus (MDV) causes tumors in chickens and results in economic costs to the poultry industry. Like most herpesviruses, this virus interacts with the host’s immune system to prevent effective control of infection; it has previously been shown that infection with MDV reduces the expression of major histocompatibility complex (MHC) class I molecules, an important component of the host defense mechanism on the surface of infected cells, likely interfering with a robust T cell response. We explored the mechanism of this effect and demonstrated that the viral gene named MDV012 was able to reduce MHC class I on two chicken cell lines. We additionally showed that a likely cellular target for MDV012’s effects is the transporter associated with antigen processing molecule named TAP upstream of MHC class I-peptide binding, as we could restore MHC I class expression by providing peptides that did not require transport by TAP to reach MHC class I. Finally, we demonstrated that the MDV012 gene is present in other members of the Mardivirus family, which suggests that genes that evade MHC class I-based immunity have been conserved within the alpha-herpesviruses for at least 100 million years.
Technical Abstract: Marek's disease virus (MDV) is a widespread a-herpesvirus of chickens that causes T cell tumors. Acute, but not latent, MDV infection has previously been shown to lead to downregulation of cell-surface MHC class I (Virology 282:198–205 (2001)), but the gene(s) involved have not been identified. Here we demonstrate that an MDV gene, MDV012, is capable of reducing surface expression of MHC class I on chicken cells. Co-expression of an MHC class I-binding peptide targeted to the endoplasmic reticulum (bypassing the requirement for the TAP peptide transporter) partially rescued MHC class I expression in the presence of MDV012, suggesting that MDV012 is a TAP-blocking MHC class I immune evasion protein. This is the first unique non-mammalian MHC class I immune evasion gene identified, and suggests that a-herpesviruses have conserved this function for at least 100 million years.