CHARACTERISATION OF A HUMAN ANTIBODY RESPONSE THAT LINKS CYTOMEGALOVIRUS INFECTION WITH SYSTEMIC LUPUS ERYTHEMATOSUS

Abstract

Human cytomegalovirus (HCMV) is a ubiquitous herpesvirus that has been linked with systemic lupus erythematosus (SLE) pathogenesis. This study focuses on the detailed characterisation of 3A11, an antibody specific for UL44. UL44 encodes the HCMV DNA polymerase processivity factor, a nuclear-resident, non-structural protein vital for HCMV DNA replication. The intracellular nature of this viral protein complicates its targeting by the humoral response. 3A11 immunoprecipitates UL44 from HCMV-infected cells with known nuclear SLE autoantigens – namely, nucleolin, dsDNA and ku70. We show that UL44 is redistributed to the cell surface during virus-induced apoptosis with these autoantigens. In a cohort of SLE patients, we also show significant associations between anti-HCMV IgG and anti-UL44 IgG antibody levels with SLE. Taken together, these results suggest a new mechanism where host nuclear antigens may be adjuvantised through their co-expression on the cell surface with a HCMV viral antigen, potentially increasing the risk of SLE development.