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Bovine herpesvirus 1 downregulates the expression of bovine MHC class I molecules
C Nataraj1, S Eidmann, M J Hariharan
1Department of Veterinary and Biomedical Sciences, University of Nebraska-Lincoln, USA.
Insights
Bovine herpesvirus 1 (BHV-1) infection selectively downregulates major histocompatibility complex (MHC) class I expression, hindering immune evasion. This viral mechanism affects MHC class I synthesis and transport, impacting host cytotoxic T-lymphocyte responses.
Area of Science:
- Immunology
- Virology
- Molecular Biology
Background:
- Bovine herpesvirus 1 (BHV-1) is known to cause immunosuppression in cattle.
- Understanding the mechanisms of viral immune evasion is crucial for developing effective vaccines and treatments.
Purpose of the Study:
- To investigate the effect of BHV-1 infection on the expression of major histocompatibility complex (MHC) class I molecules.
- To elucidate the viral components and pathways involved in BHV-1-induced immunosuppression.
Main Methods:
- Flow cytometry was used to detect MHC class I and class II expression on infected cells.
- Pulse-chase analysis was employed to study the synthesis and transport of MHC class I molecules.
- Metabolic inhibitors (cycloheximide, phosphonoacetic acid) were used to identify viral proteins responsible for downregulation.
Main Results:
- BHV-1 infection selectively downregulated MHC class I expression, while MHC class II expression remained unaffected.
- Downregulation was observed as early as 8 hours post-infection and was dose-dependent.
- Immediate early and/or early viral proteins were implicated in the downregulation of MHC class I expression.
- BHV-1 infection interfered with the synthesis, assembly, and transport of MHC class I molecules.
Conclusions:
- BHV-1 actively interferes with the host's antigen presentation machinery by downregulating MHC class I molecules.
- This downregulation likely contributes to viral immune evasion by impairing cytotoxic T-lymphocyte recognition.
- The findings provide insights into the molecular mechanisms of BHV-1 pathogenesis and immune evasion strategies.
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.