Hypothesis: Link Between Endogenous Retroviruses and Cardiovascular Disease

Bing, O.; Sirokman, Geza; Humphries, Donald E.

doi:10.1006/jmcc.1998.0723

Cited by 8 publications

(6 citation statements)

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“…Several hypotheses have so far been proposed about possible implication of HERV expression in certain pathogeneses, including autoimmune diseases such as insulin-dependent diabetes mellitus (21), tumor development, and even cardiovascular disease (22). In addition, numerous possible roles have been proposed for HERVs in reproductive physiopathology (reviewed in Ref.…”

mentioning

confidence: 99%

Inhibition of Human Endogenous Retrovirus-K10 Protease in Cell-free and Cell-based Assays

Kuhelj¹,

Rizzo²,

Chang

et al. 2001

Journal of Biological Chemistry

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A full-length and C-terminally truncated version of human endogenous retrovirus (HERV)-K10 protease were expressed in Escherichia coli and purified to homogeneity. Both versions of the protease efficiently processed HERV-K10 Gag polyprotein substrate. HERV-K10 Gag was also cleaved by human immunodeficiency virus, type 1 (HIV-1) protease, although at different sites. To identify compounds that could inhibit protein processing dependent on the HERV-K10 protease, a series of cyclic ureas that had previously been shown to inhibit HIV-1 protease was tested. Several symmetric bisamides acted as very potent inhibitors of both the truncated and full-length form of HERV-K10 protease, in subnanomolar or nanomolar range, respectively. One of the cyclic ureas, SD146, can inhibit the processing of in vitro translated HERV-K10 Gag polyprotein substrate by HERV-K10 protease. In addition, in virus-like particles isolated from the teratocarcinoma cell line NCCIT, there is significant accumulation of Gag and Gag-Pol precursors upon treatment with SD146, suggesting the compound efficiently blocks HERV-K Gag processing in cells. This is the first report of an inhibitor able to block cell-associated processing of Gag polypeptides of an endogenous retrovirus.

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mentioning

confidence: 99%

Inhibition of Human Endogenous Retrovirus-K10 Protease in Cell-free and Cell-based Assays

Kuhelj¹,

Rizzo²,

Chang

et al. 2001

Journal of Biological Chemistry

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“…Recent studies have demonstrated that endogenous retrovirus genes are closely related to various diseases, including diabetes mellitus (Marquerat et al, 2004), cardiovascular diseases (Katsumata et al, 1999;Bing et al, 1998), cancer (Shulte et al, 2000;Shiavetti et al, 2005), and lupus erythematosus (Adelman and Marchalonis, 2000;Adelman et al, 2004). However, the relationship of endogenous retrovirus genes, as well as infections with various ''pathogens'', with these diseases is reasonable to interpret as disturbance of the normal microbial function.…”

Section: Pathogenicity Infectivity and Susceptibilitymentioning

confidence: 93%

Infection: A hypothesis on active susceptibilty and species immunity with implications for aids prevention

Malyshkin

2010

Immunobiology

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“…There is evidence to indicate that diverse mobile elements are activated by a variety of stimuli, including chemicals similar to TCDD. 48,52 Particularly interesting is the correlation between elevated levels of certain endogenous retroviral transcripts in myocardium and cardiovascular disease in rats, 53,54 and the suggestion that L1Md may be involved in atherogenesis. 55 EZR1 transcript abundances were dose-dependently increased by doses of TCDD that cause cardiovascular toxicity and disrupted cardiomyocyte gene expression.…”

Section: Biological Implications Of Ezr1 Expressionmentioning

confidence: 99%

EZR1: A Novel Family of Highly Expressed Retroelements Induced by TCDD and Regulated by a NF-κB-Like Factor in Embryos of Zebrafish (Danio rerio)

Goldstone

Tokunaga²,

Schlezinger³

et al. 2012

Zebrafish

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Transcript profiling using a zebrafish heart cDNA library previously revealed abundant expressed sequence tags (ESTs) upregulated in zebrafish embryos treated with the aryl hydrocarbon receptor (AHR) agonist 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Here, we identify those ESTs as LTR-containing retroelements termed EZR1 (Expressed-Zebrafish-Retroelement group 1). EZR1 is highly redundant in the genome and includes canonical long terminal repeats (LTRs) flanking an integrase-like open reading frame and a region similar to retroviral envelope protein genes. EZR1 sequences lack reverse transcriptase, RNase H, or protease, indicating retrotransposition would be nonautonomous. No AHR binding motifs were found in the EZR1 promoter region. A putative NF-jB-binding site was found, and TCDD-treated zebrafish embryos had significantly increased levels of nuclear protein(s) binding to this sequence. Protein-EZR1 DNA complex formation was partially competed by a mammalian consensus jB sequence, consistent with NF-jB-like activation contributing to increased protein binding to this site. Mobility of the TCDD-induced protein-EZR1 complex differed from that of authentic NF-jB protein bound to the consensus jB site. The results suggest that EZR1 is regulated by interaction with NF-jB or NF-jB-like protein(s) different from the NF-jB protein binding to the consensus jB site. The nature of the NF-jB-like protein and the relationship between EZR1 induction and cardiovascular toxicity caused by TCDD warrant further investigation.

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Hypothesis: Link Between Endogenous Retroviruses and Cardiovascular Disease

Cited by 8 publications

References 0 publications

Inhibition of Human Endogenous Retrovirus-K10 Protease in Cell-free and Cell-based Assays

Inhibition of Human Endogenous Retrovirus-K10 Protease in Cell-free and Cell-based Assays

Infection: A hypothesis on active susceptibilty and species immunity with implications for aids prevention

EZR1: A Novel Family of Highly Expressed Retroelements Induced by TCDD and Regulated by a NF-κB-Like Factor in Embryos of Zebrafish (Danio rerio)

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