MHC class I expression in intestinal cells is reduced by rotavirus infection and increased in bystander cells lacking rotavirus antigen

Gavan Holloway,Barbara S Coulson,Fiona E Fleming

doi:10.1038/s41598-017-18464-x

Gavan Holloway, Barbara S Coulson + Show 1 more

Open Access

https://doi.org/10.1038/s41598-017-18464-x

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Abstract

Detection of viral infection by host cells leads to secretion of type I interferon, which induces antiviral gene expression. The class I major histocompatibility complex (MHCI) is required for viral antigen presentation and subsequent infected cell killing by cytotoxic T lymphocytes. STAT1 activation by interferon can induce NLRC5 expression, promoting MHCI expression. Rotavirus, an important pathogen, blocks interferon signalling through inhibition of STAT1 nuclear translocation. We assessed MHCI expression in HT-29 intestinal epithelial cells following rotavirus infection. MHCI levels were upregulated in a partially type I interferon-dependent manner in bystander cells lacking rotavirus antigen, but not in infected cells. MHCI and NLRC5 mRNA expression also was elevated in bystander, but not infected, cells, suggesting a transcriptional block in infected cells. STAT1 was activated in bystander and infected cells, but showed nuclear localisation in bystander cells only. Overall, the lack of MHCI upregulation in rotavirus-infected cells may be at least partially due to rotavirus blockade of interferon-induced STAT1 nuclear translocation. The reduced MHCI protein levels in infected cells support the existence of an additional, non-transcriptional mechanism that reduces MHCI expression. It is possible that rotavirus also may suppress MHCI expression in vivo, which might limit T cell-mediated killing of rotavirus-infected enterocytes.

Highlights

The class I major histocompatibility complex (MHCI) is ubiquitously expressed on the cell surface and required for recognition and subsequent killing of infected cells by cytotoxic T lymphocytes (CTLs)
We determined cell-surface MHCI (HLA-A/B/C) and intracellular rotavirus antigen levels by flow cytometry in HT-29 cell cultures inoculated with the Rhesus monkey rotavirus strain RRV, and in mock-infected HT-29 cells
The presentation of peptides via MHCI to CTL is crucial for the adaptive immune response to viral infections

Summary

Introduction

The class I major histocompatibility complex (MHCI) is ubiquitously expressed on the cell surface and required for recognition and subsequent killing of infected cells by cytotoxic T lymphocytes (CTLs). Due to the importance of MHCI in CTL recognition of virus-infected cells and the ability of rotavirus to inhibit STAT1 signaling (a process intimately linked to MHCI regulation), we assessed MHCI expression in an intestinal cell culture model following rotavirus infection. MHCI and NLRC5 mRNA expression was elevated in bystander, but not infected cells, supporting the possibility of a transcriptional block as a mechanism for the lack of MHCI elevation in infected cells. MHCI levels in infected cells were reduced compared to mock-infected cells, suggesting an additional non-transcriptional mechanism of MHCI downregulation. These findings provide preliminary evidence to support the hypothesis that inhibition of MHCI expression may be important for immune evasion by rotavirus

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