Nonhistone Chromosomal Protein Fractions of Regulatory Character Synthesized in Spleen Cells During the Immune Response
Isaac Bekhor, Carol J. Mirell, C. C. Liew in Progress in Nonhistone Protein Research, 1985
Another hypothesis may be established for fraction A (molecular weight 160,000), found in chromatin of normal, nonimmunized spleen cells, where it was depleted at the beginning of the immune reaction and again synthesized at the termination of the reaction. For this reason we suggested it to be a repressor.12,21 Enzymes causing repression of genes are well known, and the greatest attention has been paid to methylases.2 Data on methylases appears to be somewhat controversial. There are investigators who showed that the pattern of methylation of endogenous virus sequences is specifically altered during tumorigenesis.35,36 De-methylation caused activation of the oncogenic viruses and tumorigenesis, and methylation had an opposite effect, i.e., inactivation of the virus and lack of tumorigenesis. On the other hand, the opposite effect of methylation on gene activity was found to occur in X chromosomes isolated from normal human cells.37 A molecular mechanism for inactivating X chromosomes was suggested.37 Nevertheless, we suggest that the fraction A described by us may be a specific methylase or an enzyme possessing functions capable of modifying DNA structure in a specific manner that prevents gene activation.
Endogenous Proviruses
Pimentel Enrique in Oncogenes, 2020
A correlation between induced endogenous virus products and neoplastic changes in mice during hormonal mammary carcinogenesis has not been established.74 Different variants of MMTV may have different properties in relation to mammary gland tumorigenesis. For example, the MMTV variant RIII has low tumorigenic action and, on the contrary, may induce lobuloalveolar differentiation, whereas the variant C3H of the same virus shows low differentiative activity and high tumorigenic activity.75 The molecular mechanisms related to such differential effects remain undetermined but possible explanations include different sites of virus integration in the host genome and/or different sensitivity of the infected mammary cells to hormones. Additional studies are required for a better characterization of the role of endogenous and exogenous MMTV, in conjunction with genetic and hormonal factors, in mouse mammary tumorigenesis.
Cancer-Causing Viruses
Satya Prakash Gupta in Cancer-Causing Viruses and Their Inhibitors, 2014
Human endogenous retrovirus (HERV) is an HIV-like retrovirus, but where HIV is exogenous (meaning that it is originated outside the organism’s body), HERV is endogenous (meaning that it is the part of human genome). There are many families of endogenous retroviruses that exist throughout the human genome. Unlike HIV, these retroviruses purportedly integrated themselves into the genome long ago and have since accumulated mutations that have rendered them unable to produce infectious, exogenous viruses. HERVs are supposed to be “junk DNA.” The regulatory role of HERVs has been demonstrated in the liver, placenta, colon, and other locations (Bannert and Kurth 2004). One of the families of HERVs, HERV-K, is proposed to be fairly young (less than five million years old) because it still contains a complete set of genes (albeit with mutations) necessary for a retrovirus to produce infectious viruses (Bannert and Kurth 2004; Dewanneiux et al. 2006). Some HERVs have been implicated in human malignancy because of increased expression of HERV messenger RNA (mRNA) (Andersson et al. 1998), functional protein (Sauter et al. 1995), and retrovirus-like particles (Lower et al. 1993) in certain cancers. Studies are being made on the association of HERV-K with a number of cancers such as germ cell tumors like seminomas (Sauter et al. 1995, 1996), breast cancer, myeloproliferative disease, ovarian cancer (Wang-Johanning et al. 2007a, b), melanoma (Muster et al. 2003; Buscher et al. 2005), and prostate cancer (Tomlins et al. 2007). However, it could not be firmly established so far that HERV-K expression contributes to the development of any kind of cancer (McLaughlin-Drubin and Munger 2008).
Silver nanoparticles suppress forskolin-induced syncytialization in BeWo cells
Published in Nanotoxicology, 2022
Yuji Sakahashi, Kazuma Higashisaka, Ryo Isaka, Rina Izutani, Jiwon Seo, Atsushi Furuta, Akemi Yamaki-Ushijima, Hirofumi Tsujino, Yuya Haga, Akitoshi Nakashima, Yasuo Tsutsumi
Construction of the syncytiotrophoblast via the cell fusion process is essential to the placental formation process. The endogenous retrovirus genes ERVW-1 and ERVFRD-1 play an important role in facilitating this fusion process (Orendi et al. 2010). Both ERVW-1 and ERVFRD-1 have cell-fusion activity, but there are differences in their expression patterns in placental cells. The ERVW-1 is expressed in not only syncytiotrophoblast cells but also mononuclear cytotrophoblast cells, whereas ERVFRD-1 is expressed only in mononuclear cytotrophoblast cells (Malassiné et al. 2007; Holder et al. 2012). Because of this difference, it is considered that ERVFRD-1 promotes fusion between mononuclear cells and ERVW-1 is involved in fusion between syncytiotrophoblast cells and mononuclear cytotrophoblast cells (Nakamura and Imakawa 2011). Moreover, it is reported that reduced expression of Syncytin-1 and Syncytin-2 correlates with severity of preeclampsia and impaired cell fusion and differentiation in placentae from patients with intrauterine growth restriction. Furthermore, Syncytin-2 knockdown BeWo cells more suppressed syncytialization compared to Syncytin-1 knockdown BeWo cells (Vargas et al. 2009) indicating that Syncytin-2 could play a critical role in syncytinization. Present study showed that nAg10 suppressed the expression of ERVFRD-1 mRNA. Thus, it is considered that nAg10 could be involved in placental hypoplasia by suppressing the expression of ERVFRD-1.
Perivascular tissue resident memory T cells as therapeutic target in multiple sclerosis
Published in Expert Review of Neurotherapeutics, 2020
Joost Smolders, Nina L. Fransen, Cheng-Chih Hsiao, Jörg Hamann, Inge Huitinga
An urgent question is the identification of the antigen(s) against which T-cell responses in MS and specifically the TRM-cell response is mounted. In other tissues, TRM cells have been mostly studied in and associated with virus infections [45,46]. Therefore, a viral antigen appears tempting. A vast body of literature associates MS with Epstein-Barr virus (EBV) infection[108]. Accumulation of EBV-infected B cells and EBV-directed CD8+ T cells has been described in MS CSF [109–111] and in MS lesions [76,85,112–114], although the reproducibility of these findings has also been debated [115–117]. Other viruses have also been associated with MS, including human herpesvirus (HHV)-6[118]. Moreover expression of endogenous retrovirus sequences has been described in MS lesions[119], which may also elicit a CD8+ T-cell response[120]. Alternatively, a potential role of autoantigen-directed TRM cells in autoimmune diseases has not been explored extensively yet.
Genomic and immunologic correlates of LAG-3 expression in cancer
Published in OncoImmunology, 2020
Anshuman Panda, Jeffrey A. Rosenfeld, Eric A. Singer, Gyan Bhanot, Shridar Ganesan
The expression of normally silenced endogenous retroviral RNAs has been shown to be a potential mechanism of activation of innate immune signaling.23 We recently showed that expression of the potentially immunogenic endogenous retrovirus ERV3-2 is correlated with overall immune infiltration in 14 solid cancer types.24 To determine whether ERV expression is associated with LAG-3 expression, we tested for correlation between ERV3-2 expression and LAG-3 expression in these 14 cancer types. In 11 of the 14 cancer types, ERV3-2 expression was significantly (P < .05) correlated with LAG-3 expression (Figure 3(e)), suggesting that ERV3-2 expression may be a predictor of response to LAG-3 blockade in these cancer types. In addition to LAG-3, ERV3-2 expression was also associated with the upregulation of PD-1 and CTLA-4 pathways in most of these cancer types,24 suggesting the coordinated upregulation of multiple immune checkpoint genes in ERV-expressing tumors. In contrast, ERV3-2 expression was associated with overexpression of other checkpoint genes in a more cancer type-specific manner, such as the BTLA-HVEM pathway in only six cancer types and the TIM3-GAL9 pathway in only five cancer types (Figure 3(f)). A pan-cancer analysis to identify ERVs whose expressions correlated (Spearman Rho > 0, P < .05) or anti-correlated (Spearman Rho < 0, P < .05) with LAG-3 expression showed that ERV3-2 expression is correlated with LAG-3 expression in more cancer types than any other ERV (Supplementary Figure 5). Association between ERV3-2 expression and response to LAG-3 blockade with or without PD-1 blockade in these cancer types should be investigated in clinical trials.
Related Knowledge Centers
- Gene Expression
- Genome
- Germline
- Provirus
- Retrotransposon
- Retrovirus
- Transposable Element
- Endogenous Viral Element
- Gene
- Regulation of Gene Expression