Human cytomegalovirus pp65 peptide-induced autoantibodies cross-reacts with TAF9 protein and induces lupus-like autoimmunity in BALB/c mice.

Publisher: Nature Publishing Group Country of Publication: England NLM ID: 101563288 Publication Model: Electronic Cited Medium: Internet ISSN: 2045-2322 (Electronic) Linking ISSN: 20452322 NLM ISO Abbreviation: Sci Rep Subsets: MEDLINE

Original Publication: London : Nature Publishing Group, copyright 2011-

Autoantibodies/*metabolism ; Cytomegalovirus/*metabolism ; Lupus Erythematosus, Systemic/*immunology ; TATA-Binding Protein Associated Factors/*immunology ; Transcription Factor TFIID/*immunology ; Viral Matrix Proteins/*immunology; Animals ; Case-Control Studies ; Cross Reactions ; Cytomegalovirus/immunology ; DNA/immunology ; Disease Models, Animal ; Humans ; Lupus Erythematosus, Systemic/metabolism ; Mice ; Mice, Inbred BALB C ; Molecular Mimicry ; Proof of Concept Study ; Viral Matrix Proteins/chemistry

Human cytomegalovirus (HCMV) has been linked to the triggering of systemic lupus erythematosus (SLE). We proposed that B cell epitope region of HCMV phosphoprotein 65 (HCMVpp65) 422-439 mimics an endogenous antigen and initiates lupus-like autoimmunity. Amino acid homology between HCMVpp65 422-439 and TAF9 134-144 (TATA-box binding protein associated factor 9, TAF9) was investigated using a similarity search in NCBI protein BLAST program (BLASTP). A murine model was used to confirm their antigenicity and ability to induce lupus-like symptoms. HCMVpp65 422-439 induced immune responses with the presence of specific antibodies against HCMVpp65 422-439 and TAF9 134-144 , as well as anti-nuclear and anti-double-stranded (ds)DNA antibodies that are characteristic of SLE. In addition, the majority of HCMVpp65 422-439 and TAF9 134-144 immunized mice developed proteinuria, and their renal pathology revealed glomerulonephritis with typical abnormalities, such as mesangial hypercellularity and immune complex deposition. Immunoglobulin eluted from the glomeruli of HCMVpp65 422-439 immunized mice showed cross-reactivity with TAF9 134-144 and dsDNA. Increased anti-TAF9 antibody activity was also observed in the sera from SLE patients compared with healthy people and disease controls. Molecular mimicry between HCMVpp65 peptide and host protein has the potential to drive lupus-like autoimmunity. This proof-of-concept study highlights the mechanisms underlying the link between HCMV infection and the induction of SLE.

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0 (Autoantibodies)
0 (TAF9 protein, human)
0 (TATA-Binding Protein Associated Factors)
0 (Transcription Factor TFIID)
0 (Viral Matrix Proteins)
0 (cytomegalovirus matrix protein 65kDa)
9007-49-2 (DNA)

Date Created: 20200617 Date Completed: 20201209 Latest Revision: 20210615

20240829

PMC7295797

10.1038/s41598-020-66804-1

32541894