Regulation of MHC class I after infection by pseudorabies virus.

摘要

Many herpes viruses have been shown to regulate cell surface expression of major histocompatibility class I (MHC I) on the surface of cells. These include pseudorabies virus (PRV), herpes simplex virus, bovine herpes virus type-1 (BHV-1), varicella zoster virus (VZV), Epstein-Barr virus, and murine and human cytomegalovirus. The viral gene products involved in regulating MHC I during infections by PRV,VZV and BHV-1 have not yet been identified. Therefore, we characterized how PRV regulates MHC I during infection and the viral gene products that are involved.;Our data suggests that there are at least three viral gene products that regulate MHC I expression on the surface of cells. These gene products can act in an allele-specific manner such that a proportion of the MHC I on the cell surface is affected by PRV infection. For example, during infection of a murine fibroblast cell line, L929 cells, PRV infection does not alter the total amount of MHC I on the surface of cells. Instead it increases the expression of the Kk allele and decreases the expression of the D k allele. This effect is not isolated to infections of L929 cells as infections of one swine kidney cell line, PK15, results in the decrease of a proportion of the MHC I early in infection and the rest of the MHC I late in infection. In contrast, infections of another swine kidney cell line, Max, results in the increase of one MHC I allele but no change in another MHC I allele.;PRV utilizes at least one viral gene product to increase MHC I and two viral gene products to cell decrease MHC I. One early viral gene product acts to inhibit MHC I by reducing the stability of the complex. This gene product is regulated by the Us3 gene. A second, late gene product reduces MHC I by interfering with the synthesis of the complex. This gene product is regulated by the UL41 protein. A third viral gene product induces the expression of MHC I on the cell surface. This viral gene product is mutant in the vaccine strain, PRV-Bartha.