Downregulation of HLA-I by the molluscum contagiosum virus mc080 impacts NK-cell recognition and promotes CD8+ T-cell evasion
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Molluscum contagiosum virus (MCV) is a common cause of benign skin lesions in young children and currently the only endemic human poxvirus. Following the infection of primary keratinocytes in the epidermis, MCV induces the proliferation of infected cells and this results in the production of wart-like growths. Full productive infection is observed only after the infected cells differentiate. During this prolonged replication cycle the virus must avoid elimination by the host immune system. We therefore sought to investigate the function of the two major histocompatibility complex class-I-related genes encoded by the MCV genes mc033 and mc080. Following insertion into a replication-deficient adenovirus vector, codon-optimized versions of mc033 and mc080 were expressed as endoglycosidase-sensitive glycoproteins that localized primarily in the endoplasmic reticulum. MC080, but not MC033, downregulated cell-surface expression of endogenous classical human leucocyte antigen (HLA) class I and non-classical HLA-E by a transporter associated with antigen processing (TAP)-independent mechanism. MC080 exhibited a capacity to inhibit or activate NK cells in autologous assays in a donor-specific manner. MC080 consistently inhibited antigen-specific T cells being activated by peptide-pulsed targets. We therefore propose that MC080 acts to promote evasion of HLA-I-restricted cytotoxic T cells.
Journal of General Virology;
Elasifer, H., Wang, E.C., Prod’homme, V., Davies, J., Forbes, S., Stanton, R.J., Patel, M., Fielding, C.A., Roberts, D., Traherne, J.A. and Gruber, N. (2020) 'Downregulation of HLA-I by the molluscum contagiosum virus mc080 impacts NK-cell recognition and promotes CD8+ T-cell evasion', Journal of General Virology, p.jgv001417.
Article published in Journal of General Virology on 08 June 2020, available open access at: https://doi.org/10.1099/jgv.0.001417.
Cardiff Metropolitan University (Grant ID: Cardiff Metropolian (Internal))
Dr H Elasifer’s PhD studentship was funded by a grant from the Libyan Ministry of Higher Education and Scientific Research. The project received funding from Wellcome Trust and the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation programme (grant agreement No. 695551).