Differential Regulation of D^kand K^kMajor Histocompatibility Complex Class I Proteins on the Cell Surface after Infection of Murine Cells by Pseudorabies Virus

Abstract

After pseudorabies virus (PRV) infection of murine L929 cells, the cell surface expression of major histocompatibility complex (MHC) class I proteins changes such that the total amount of MHC class I molecules remains relatively constant but the levels of the individual alleles Dk and Kk vary. This is an active process involving at least three PRV gene products that act in an allele-specific manner such that cell surface expression of MHC class I Dk is decreased and that of Kk is increased. Our results indicate that an early gene product mediates the overall reduction in Dk protein and a late gene product which is mutant in the attenuated PRV strain Bartha mediates the increase in Kk protein. We provide additional evidence for a third gene product involved in the regulation of the synthesis of both the Dk and Kk proteins. In addition, we show that the early decrease in the Dk protein is not due to a block in synthesis or processing of the complex through the secretory system.

The Attenuated Pseudorabies Virus Vaccine Strain Bartha K61: A Brief Review on the Knowledge Gathered during 60 Years of Research

“…MHC class I molecules present viral antigens and are recognized by cytotoxic T lymphocytes and natural killer (NK) cells. Hence, differential expression of MHC class I alleles might alter immune recognition of these infected cells [87]. Using both mice and rats, it was observed that neuronal infection of Bartha K61 induces a rapid recruitment of microglial cells to infected brain lesions, as part of the host response to the infection [88,89].…”

The UL41-encoded virion host shutoff (vhs) protein and vhs-independent mechanisms are responsible for down-regulation of MHC class I molecules by bovine herpesvirus 1

“…At present, viral gene products that subvert the MHC class I-restricted antigen presentation pathway have been identified for HSV1 and -2 (York et al , 1994 ), murine (MCMV; Reusch et al , 1999 ) and human cytomegalovirus (HCMV; Ahn et al , 1996 , 1997 ; Hengel et al , 1997 ; Jones et al , 1995 b , 1996 ; Wiertz et al , 1996 a , b ), human herpesvirus-8 (Coscoy & Ganem, 2000 ; Ishido et al , 2000 ), Epstein–Barr virus (Levitskaya et al , 1995 ) and gammaherpesvirus-68 (Stevenson et al , 2000 ). The varicelloviruses VZV (Cohen, 1998 ), BHV1 (Hariharan et al , 1993 ) and PrV (Sparks-Thissen & Enquist, 1999 ) have also been found to down-regulate MHC class I expression, but the viral gene products involved remain to be identified. None of these varicelloviruses code for proteins homologous to the presently known gene products from other (herpes) viruses that interfere with MHC class I antigen presentation.…”

Resveratrol Inhibits Pseudorabies Virus Replication by Targeting IE180 Protein

“…IE180 is a phosphorylated protein localized in the nucleus of an infection. It is translated in the cytoplasm and then returns to the nucleus to interact with DNA to activate transcription ( Sparks-Thissen and Enquist, 1999 ). According to the characteristic of IE180, we speculated that resveratrol might inhibit the function of IE180 protein, thus blocking the downstream gene expression.…”