Bovine Herpesvirus 1 Downregulates the Expression of Bovine MHC Class I Molecules

Abstract

The mechanism of immunosuppression induced by bovine herpesvirus 1 (BHV-1) was investigated by studying the effects of the virus on the expression of major histocompatibility complex (MHC) class I molecules. After infection with the virus, the expression of class I molecules was detected by flow cytometry and pulse-chase analysis. A selective downregulation of expression of class I molecules was seen in the infected cells, while the class II expression remained unaffected. The reduction in surface expression was evident as early as 8 hours postinfection, reaching significant levels by 12 hours. The downregulation was seen with a multiplicity of infection as low as 0.1. A modified live vaccine strain of BHV-1 also induced the downregulation of class I expression. Analysis of the viral proteins(s) involved in this downregulation with metabolic inhibitors (cycloheximide or phosphonoacetic acid), suggested that the immediate early and/or early proteins of the virus mediate this effect. Pulse-chase analysis revealed that the synthesis of the class I heavy chain, and the assembly/transport of class I molecules were affected by the virus infection. These results suggest that BHV-1 interferes with the molecular mechanisms involved in the synthesis, and assembly/transport of MHC-class I molecules. This interference with the class I antigen processing pathway might help the virus to evade the cytotoxic T-lymphocyte response of the host.

Bovine herpesvirus 1 infection and infectious bovine rhinotracheitis

“…In order to diminish the detection and the elimination of virus-infected cells by cytotoxic T lymphocytes, BoHV-1 was shown to down-regulate antigen presentation by the class I major histocompatibility complex (MHC class I) [95,96,115,146]. Two independent mechanisms are responsible for down-regulation of MHC class I molecules.…”

Non-classical Major Histocompatibility Complex Class Makes a Crucial Contribution to Reproduction in the Dairy Cow

“…MHC class I molecules are composed of a single membrane-spanning heavy chain (including α1, α2 and α3 domains) paired with the soluble protein β2 microglobulin (β2m), which construct a groove in their membrane distal domain (α1α2 or α1β2) that binds peptides in order to display them to the T cells of the cellular immune response [45]. MHC-I heavy chain RNA could be downregulated by bovine papillomavirus E5 oncoproteins and bovine herpes virus [46,47]. A bovine B cell line infected by bovine leukemia virus (BL3.1) is distinguished by a loss of expression of surface MHC-I, which correlates with a diminution in MHC-I heavy chain transcription due to loss of a transactivator [48].…”

How Mannheimia haemolytica defeats host defence through a kiss of death mechanism

“…The latter is known to decrease host defence amongst others by diminishing the activities of T lymphocytes, B lymphocytes, monocytes and macrophages [24,67] and by interfering with the host's antigen presentation machinery to evade the host's immune response in vivo [74,134]. Moreover, it has been shown that leukocyte exposure to inflammatory cytokines released in response to BHV-1 infection (interleukin-1 beta, interleukin-8, tumour necrosis factor alpha and interferon gamma) can modulate the migration and functional activation of bovine leukocytes [26,105,106].…”