Sequence Analysis of Human Endogenous Retrovirus Clone 4-1 in Systemic Lupus Erythematosus

Ogasawara, Hitoshi; Hishikawa, Takashi; Sekigawa, Iwao; Hashimoto, Hiroshi; Yamamoto, Naoki; Maruyama, Naoki

doi:10.3109/08916930108994105

Cited by 41 publications

(31 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Expression of HERV-E4-1 appears to be increased in patients with SLE due to DNA hypomethylation [56]. Interestingly, higher expression levels in SLE lymphocytes correlate with production of U1 snRNP [57] which includes a 70 kDa protein with a region of homology to gag antigens of infectious and ERV [24,58].…”

Section: Activation Of Erv By Dna Demethylationmentioning

confidence: 99%

Molecular mimicry and immunomodulation by the HRES-1 endogenous retrovirus in SLE

et al. 2008

View full text Add to dashboard Cite

Genetic and environmental factors are believed to influence development of systemic lupus erythematosus (SLE). Endogenous retroviruses (ERV) correspond to the integrated proviral form of infectious retroviruses, which are trapped within the genome due to mutations. ERV represent a key molecular link between the host genome and infectious viral particles. ERV-encoded proteins are recognized by antiviral immune responses and become targets of autoreactivity. Alternatively, ERV protein may influence cellular processes and the life cycle of infectious viruses. As examples, the HRES-1 human ERV encodes a 28-kDa nuclear autoantigen and a 24-kDa small GTP-ase, termed HRES-1/Rab4. HRES-1/p28 is a nuclear autoantigen recognized by crossreactive antiviral antibodies, while HRES-1/Rab4 regulates surface expression of CD4 and the transferrin receptor (TFR) through endosome recycling. Expression of HRES-1/Rab4 is induced by the tat gene of HIV-1, which in turn down-regulates expression of CD4 and susceptibility to reinfection by HIV-1. CD4 and the TFR play essential roles in formation of the immunological synapse (IS) during normal T-cell activation by a cognate MHC class II peptide complex. The key intracellular transducer of T-cell activation, Lck, is brought to the IS via binding to CD4. T-cell receptorζ (TCRζ) chain binds to the TFR. Abnormal T-cell responses in SLE have been associated with reduced lck and TCRζ chain levels. HRES-1 is centrally located on chromosome 1 at q42 relative to lupus-linked microsatellite markers and polymorphic HRES-1 alleles have been linked to the development of SLE. 1q42 is one of the three most common fragile sites in the human genome, and is inducible by DNA demethylation, a known mechanism of retroviral gene activation. Molecular mimicry and immunomodulation by a ERV, such as HRES-1, may contribute to self-reactivity and abnormal Tand B-cell functions in SLE. (Table I). HERVs are commonly designated as HERV followed by a single letter amino acid code corresponding to a tRNA. The 3′ terminus of tRNA is predicted to initiate reverse transcription by annealing to an 18 nucleotide long primer-binding site (PBS) at the 5′ LTR. While expression of murine ERV can lead to production of infectious virus and cause viremia, no production of infectious virion has been documented by HERV. High copy number of most ERV families makes it difficult to distinguish which members of a group are expressed. Although, no single provirus with intact LTRs and uninterrupted gag, pol, and env ORFs has been identified, the HERV-K ERV, as a family, has been shown to encode gag HHS Public Access Author Manuscript Author ManuscriptAuthor ManuscriptAuthor Manuscript the LTR region, is functionally analogous to the HIV-1 rev and HTLV-I/II rex proteins. HERV-K rev binds to both the nuclear export factor Crm1 and to a cis-acting viral RNA to activate nuclear export of unspliced RNAs [39]. Alternatively, the HERV-K LTR is also recognized by HIV-1 rev, suggesting a potential interaction between these exogeneous a...

show abstract

Section: Activation Of Erv By Dna Demethylationmentioning

confidence: 99%

Molecular mimicry and immunomodulation by the HRES-1 endogenous retrovirus in SLE

et al. 2008

View full text Add to dashboard Cite

show abstract

“…The LTRs of HERV-E contain a promoter known to affect transcription of several cellular genes. Moreover, HERV-E transcripts have been seen in both normal and diseased tissues (52,65). To retrieve HERV-E(4-1) Env-encoding sequences, the same type of TBLASTN search that was initially made with ERV3 Env was also made with HERV-E Env.…”

Section: Downloaded Frommentioning

confidence: 99%

ERV3 and Related Sequences in Humans: Structure and RNA Expression

Andersson¹,

Yun²,

Sperber

et al. 2005

J Virol

View full text Add to dashboard Cite

The ERV3 locus at chromosome 7q11 is a much studied human endogenous retroviral (HERV) sequence, owing to an env open reading frame (ORF) and placental RNA and protein expression. An analysis of the human genome demonstrated that ERV3 is one of a group of 41 highly related elements (ERV3-like HERVs) which use proline, isoleucine, or arginine tRNA in their primer binding sites. In addition to elements closely related to ERV3, the group included the previously known retinoic acid-inducible element, RRHERVI, also referred to as HERV15, but was separate from the related HERV-E elements. The ERV3-like elements are defective. The only element with an ORF among gag, pro, pol, and env genes was the env ORF of the original ERV3 locus. A search in dbEST revealed ERV3 RNA expression in placenta, skin, carcinoid tumor, and adrenal glands. Expression was also studied with newly developed real-time quantitative PCRs (QPCR) of ERV3 and HERV-E(4-1) env sequences. Results from a novel histone 3.3 RNA QPCR result served as the expression control. QPCR results for ERV3 were compatible with previously published results, with a stronger expression in adrenal gland and placenta than in 15 other human tissues. The expression of the envelope (env) of ERV3 at chromosome 7q11 was also studied by using stringent in situ hybridization. Expression was found in corpus luteum, testis, adrenal gland, Hassal's bodies in thymus, brown fat, pituitary gland, and epithelium of the lung. We conclude that ERV3 env is most strongly expressed in adrenal and sebaceous glands as well as in placenta.

show abstract

“…When we considered the following data such as FGS/Kist mice are inbred mice (24), they have immune complexes and retroviral envelop antigen in their kidney (25), the morphology of renal disease of FGS/Kist mice resemble the pathology of the kidney disease of human immunodeficiency acquired disease (personal communication), there is a possibility that the disease of FGS/Kist mice might be related with endogenous retroviruses (ERV). Some diseases such as rheumatoid arthritis, systemic lupus erythematosus, which are known to related with ERV, have some gender preferences (35)(36)(37). Therefore, if the disease of FGS/Kist mice was related with ERV, there could be some differences in the development of the disease in male and female.…”

Section: Discussionmentioning

confidence: 99%

Pirfenidone Suppressed the Development of Glomerulosclerosis in the FGS/Kist mouse

et al. 2003

View full text Add to dashboard Cite

Pirfenidone (PFD) is a newly developed anti-fibrotic agent. We evaluated the effect of PFD for the prevention of renal fibrosis using a spontaneous progressive glomerulosclerosis animal model, FGS/Kist mice. Male and female FGS/Kist mice were fed a diet containing 0.5% PFD or the same control diet (CD) without PFD, for 1, 2, or 3-month periods. Body weight was monitored for the general effect of PFD on the mice. Proteinuria and glomerular filtration rate (GFR) were evaluated for renal function. The sclerosis index was examined for the morphological changes. There were no significant changes in body weight between the PFD and control groups in both sexes. Proteinuria levels were low in all the PFD groups compared to the corresponding CD groups. The sclerosis scores were also reduced in both sexes of the 3-month PFD groups (p<0.05), and glomerular filtration rates were increased in both sexes of the 3-month PFD groups compared to the CD groups. The treatment of PFD for 1 or 2-month periods did not have statistic significances but the treatment for 3 months had statistic significances in sclerosis and GFR compared to CD groups. These results suggested that long-term administration of PFD suppressed the progression of glomerulosclerosis and improved renal function of the FGS/Kist mice.

show abstract

Sequence Analysis of Human Endogenous Retrovirus Clone 4-1 in Systemic Lupus Erythematosus

Cited by 41 publications

References 28 publications

Molecular mimicry and immunomodulation by the HRES-1 endogenous retrovirus in SLE

Molecular mimicry and immunomodulation by the HRES-1 endogenous retrovirus in SLE

ERV3 and Related Sequences in Humans: Structure and RNA Expression

Pirfenidone Suppressed the Development of Glomerulosclerosis in the FGS/Kist mouse

Contact Info

Product

Resources

About