Aberrant Epstein-Barr viral infection in systemic lupus erythematosus.
Serologic association, cross-reactivity of select EBV-specific antibodies with SLE autoantigens, SLE-like autoimmunity after immunization with EBV peptides, increased EB viral load in SLE patients, and SLE-specific alterations in EBV humoral and cellular immunity implicate Epstein-Barr virus (EBV) in the development of systemic lupus erythematosus (SLE). To investigate SLE-specific differences in EBV gene expression, levels of eight EBV genes were compared between SLE patients and controls by using both ex vivo-infected and un-manipulated peripheral blood mononuclear cells (PBMCs). Expression levels of mRNA were significantly greater by Wilcoxen signed rank test in the ex vivo-infected SLE patient-derived cells for 4 of 8 EBV genes, including BLLF1, 3.2-fold (p<0.004); LMP-2, 1.7-fold (p<0.008); EBNA-1, 1.7-fold (p<0.01); and BcRF1, a proposed DNA binding protein, 1.7-fold (p<0.02). The frequency of LMP-1 gene expression was significantly greater by Chi square analysis in the peripheral blood from SLE patients than controls (44% of patients, 10% of controls p<0.05). PBMCs from SLE patients had greater expression of latent genes as well as increased expression of both latent and lytic genes after infection, suggesting that EBV may participate in SLE etiology through several mechanisms. Such altered infection patterns may contribute to the increased levels of EBV and the molecular mimicry seen in sera from SLE patients.
Poole
Brian D
BD
Department of Microbiology and Molecular Biology, Brigham Young University, Provo, UT, United States.
Templeton
Amanda K
AK
Guthridge
Joel M
JM
Brown
Eric J
EJ
Harley
John B
JB
James
Judith A
JA
D000328:Adult; D000956:Antigens, Viral / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D020031:Epstein-Barr Virus Infections / Q000150:complications* / Q000276:immunology / Q000821:virology; D005260:Female; D004854:Herpesvirus 4, Human / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000209:etiology* / Q000276:immunology / Q000821:virology*; D008297:Male; D008875:Middle Aged; D018716:Molecular Mimicry; D016133:Polymerase Chain Reaction / Q000379:methods; D015854:Up-Regulation; D014764:Viral Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*
D000956:Antigens, Viral; D014764:Viral Proteins