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Wolverhampton Intellectual Repository and E-Theses > School of Applied Sciences > Research Centre in Applied Sciences  > Applied Microbiology Research Group > A role for human endogenous retrovirus-K (HML-2) in rheumatoid arthritis: investigating mechanisms of pathogenesis.

Please use this identifier to cite or link to this item: http://hdl.handle.net/2436/117096
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Title: A role for human endogenous retrovirus-K (HML-2) in rheumatoid arthritis: investigating mechanisms of pathogenesis.
Authors: Freimanis, Graham L.
Hooley, Paul
Ejtehadi, H Dava
Ali, H. A.
Veitch, A.
Rylance, P.
Alawi, A.
Axford, J.
Nevill, Alan M.
Murray, Paul G.
Nelson, Paul N.
Citation: Clinical and experimental immunology, 160 (3):340-7
Publisher: Wiley-Blackwell
Journal: Clinical and experimental immunology
Issue Date: 2010
URI: http://hdl.handle.net/2436/117096
DOI: 10.1111/j.1365-2249.2010.04110.x
PubMed ID: 20345981
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.
Type: Article
Language: en
MeSH: 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
ISSN: 1365-2249
Appears in Collections: Applied Microbiology Research Group
Cancer Research Group

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