A role for human endogenous retrovirus-K (HML-2) in rheumatoid arthritis: Investigating mechanisms of pathogenesis

Freimanis, G. and Hooley, P. and Ejtehadi, H.D. and Ali, H.A. and Veitch, A. and Rylance, P.B. and Alawi, A. and Axford, J. and Nevill, A. and Murray, P.G. and Nelson, P.N. (2010) A role for human endogenous retrovirus-K (HML-2) in rheumatoid arthritis: Investigating mechanisms of pathogenesis. Clinical and Experimental Immunology, 160 (3). pp. 340-347. ISSN 00099104 (ISSN)

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Abstract

Human endogenous retroviruses (HERVs) are remnants of ancient retroviral infections within the human genome. These molecular fossils draw parallels with present-day exogenous retroviruses and have been linked previously with immunopathology within rheumatoid arthritis (RA). Mechanisms of pathogenesis for HERV-K in RA such as molecular mimicry were investigated. To clarify a role for HERVs in RA, potential autoantigens implicated in autoimmunity were scanned for sequence identity with retroviral epitopes. Short retroviral peptides modelling shared epitopes were synthesized, to survey anti-serum of RA patients and disease controls. A novel real-time polymerase chain reaction (PCR) assay was also developed to quantify accurately levels of HERV-K (HML-2) gag expression, relative to normalized housekeeping gene expression. Both serological and molecular assays showed significant increases in HERV-K (HML-2) gag activity in RA patients, compared to disease controls. The real-time PCR assay identified significant up-regulation in HERV-K mRNA levels in RA patients compared to inflammatory and healthy controls. Exogenous viral protein expression and proinflammatory cytokines were also shown to exert modulatory effects over HERV-K (HML-2) transcription. From our data, it can be concluded that RA patients exhibited significantly elevated levels of HERV-K (HML-2) gag activity compared to controls. Additional factors influencing HERV activity within the synovium were also identified. The significant variation in RA patients, both serologically and transcriptionally, may be an indication that RA is an umbrella term for a number of separate disease entities, of which particular HERV polymorphisms may play a role in development. © 2010 British Society for Immunology.

Item Type: Article
Uncontrolled Keywords: Arthritis, Autoimmunity, Retrovirus, Rheumatology, Virus, autoantigen, cytokine, epitope, Gag protein, messenger RNA, article, autoimmunity, blood sampling, clinical article, controlled study, enzyme linked immunosorbent assay, gene expression, genetic polymorphism, genetic transcription, human, human cell culture, inflammation, nonhuman, nucleotide sequence, pathogenesis, priority journal, real time polymerase chain reaction, Retrovirus, rheumatoid arthritis, RNA extraction, serology, synoviocyte, synovium, upregulation, Adult, Aged, Arthritis, Rheumatoid, Autoantigens, Endogenous Retroviruses, Epitopes, Female, Gene Expression Regulation, Viral, Gene Products, gag, Humans, Male, Middle Aged, Molecular Mimicry, Peptides, Polymorphism, Genetic, RNA, Messenger, RNA, Viral, Synovial Membrane, Transcription, Genetic
Subjects: A300 Clinical Medicine
B900 Others in Subjects allied to Medicine
Divisions: UoA Collections > UoA 03: Allied Health Professions, Dentistry, Nursing & Pharmacy
Depositing User: Yasser Nawaz
Date Deposited: 22 May 2017 08:44
Last Modified: 22 May 2017 08:44
URI: http://www.open-access.bcu.ac.uk/id/eprint/2833

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