Please use this identifier to cite or link to this item: https://doi.org/10.1038/s41598-019-46329-y
Title: Characterisation of a human antibody that potentially links cytomegalovirus infection with systemic lupus erythematosus.
Authors: Neo, Jie Ying Jacklyn 
Wee, Seng Yin Kelly
Bonne, Isabelle 
Tay, Sen Hee 
Raida, Manfred
Jovanovic, Vojislav 
Fairhurst, Anna-Marie
Lu, Jinhua 
Hanson, Brendon J
MacAry, Paul A 
Issue Date: 10-Jul-2019
Publisher: Springer Science and Business Media LLC
Citation: Neo, Jie Ying Jacklyn, Wee, Seng Yin Kelly, Bonne, Isabelle, Tay, Sen Hee, Raida, Manfred, Jovanovic, Vojislav, Fairhurst, Anna-Marie, Lu, Jinhua, Hanson, Brendon J, MacAry, Paul A (2019-07-10). Characterisation of a human antibody that potentially links cytomegalovirus infection with systemic lupus erythematosus.. Sci Rep 9 (1) : 9998-. ScholarBank@NUS Repository. https://doi.org/10.1038/s41598-019-46329-y
Abstract: Human cytomegalovirus (HCMV) is a ubiquitous herpesvirus that has been linked with the development of systemic lupus erythematosus (SLE). Thus far, molecular mimicry has been implicated as the principal mechanism that explains this association. In this study, we characterise a potential alternative process whereby HCMV contributes to SLE. In a cohort of SLE patients, we show a significant association between HCMV infection and SLE through a human antibody response that targets UL44. UL44 is an obligate nuclear-resident, non-structural viral protein vital for HCMV DNA replication. The intracellular nature of this viral protein complicates its targeting by the humoral response - the mechanism remains unresolved. To characterise this response, we present a thorough molecular analysis of the first human monoclonal antibody specific for UL44 derived from a HCMV seropositive donor. This human antibody immunoprecipitates UL44 from HCMV-infected cells together with known nuclear-resident SLE autoantigens - namely, nucleolin, dsDNA and ku70. We also show that UL44 is redistributed to the cell surface during virus-induced apoptosis as part of a complex with these autoantigens. This phenomenon represents a potential mechanism for the bystander presentation of SLE autoantigens to the humoral arm of our immune system under circumstances that favour a break in peripheral tolerance.
Source Title: Sci Rep
URI: https://scholarbank.nus.edu.sg/handle/10635/157004
ISSN: 2045-2322
2045-2322
DOI: 10.1038/s41598-019-46329-y
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