Naturally Occurring Alkaloids with Anti-HIV Activity
Namrita Lall in Medicinal Plants for Cosmetics, Health and Diseases, 2022
The amino acid 2-amino-3-(3’,4’-dihydroxyphenyl) propionic acid (DOPA) is a key precursor to a broad variety of structurally unique alkaloids in marine invertebrates. A few DOPA-derived pyrrole alkaloids—namely, baculiferins A-O (60–74), purpurone (75) and ningalin A (76)—were isolated from the alcoholic extract of Chinese marine sponge Iotrochota baculifera Ridley (Figure 20.8). Alkaloids 60–74 displayed good anti—HIV-1 activity against IIIB strain in human T cells (MT-4) and a HeLa cell clone expressing human CD4 and HIV-LTR-β gal (MAGI or HeLa-CD4-LTR-b- gal cells). The IC50 values for these alkaloids against MT-4 cells were found to be in the range of 1.4–8.4 μg/mL, while that against MAGI cells was found to be in the range of < 0.1–4.4 μg/mL. The IC50 for purpurone (75) was found to be > 25 μg/mL in both the host cells (MT-4 and MAGI), while alkaloid 76 was not tested. These alkaloids act by inhibiting the recombinant gp41 (a transmembrane protein of HIV-1), viral infectivity factor of HIV-1 (Vif) and a human innate intracellular anti-viral factor (APOBEC3G) as it showed interesting binding affinity to these target proteins (Fan et al., 2010).
Current Application of CRISPR/Cas9 Gene-Editing Technique to Eradication of HIV/AIDS
Yashwant Pathak in Gene Delivery, 2022
As the restriction factors act on HIV-1 at different stages within the life cycle, and therefore the expression of some restriction factors is merely induced by infection, better understanding of the molecular mechanisms of HIV-1 counteraction with restriction factors will provide more options and rationale for the look of CRISPR/Cas9. Additionally, several restriction factors have dual functions in immunomodulation and different expression levels in various cells, which makes its more complex within the activation of gene expression by CRISPR/Cas9. However, the enforced long-term activation of restriction factors expression has side effects in vivo and desires further investigation. For instance, the virus restriction factor APOBEC3G, which is induced by IFNs, has an antiviral effect on HIV-1 and HBV. These are different expression levels in various cells. But their activated expression in several cells over an extended period of your time isn’t bound to exhibit deleterious effects in vivo just because it has not been reported at the present. [71]
Viral subversion of APOBEC3s: Lessons for anti-tumor immunity and tumor immunotherapy
Published in International Reviews of Immunology, 2018
Faezeh Borzooee, Mahdi Asgharpour, Emma Quinlan, Michael D. Grant, Mani Larijani
APOBEC3G (A3G) and APOBEC3F (A3F) are DNA-editing enzymes expressed in CD4+ T cells, macrophages, and dendritic cells, which are targets of HIV infection.9 A3G/F convert cytidine (C) to uridine (U) in signature trinucleotide mutational “hotspots” (CCC and TCC for A3G; TTC for A3F) in the reverse transcribed single stranded (ssDNA) copy of the HIV genome, registering as guanine (G) to adenine (A) substitutions in the coding DNA strand.10–19 In addition to mutating the viral genome, A3G/F physically interfere with reverse transcription, RNA encapsidation or host genome integration of the viral genome. Through these collective activities, A3G/F diminish the replication capacity of HIV.20–33 Since their discovery 15 years ago and for the majority of time since then, A3G/F have been considered innate immune anti-viral host restriction factors.10,34–41 Within the A3 family, A3G/F have been the most well-studied members for viral restriction, because they carry the most potent HIV restriction ability. However, the other A3 family members (A3A, B, C, D, H) also exhibit varying but generally lesser degrees of anti-viral activities.42,43
MiRNAs roles in the diagnosis, prognosis and treatment of colorectal cancer
Published in Expert Review of Proteomics, 2019
Daniel G. Sur, Marius Colceriu, Genel Sur, Cornel Aldea, Ciprian Silaghi, Gabriel Samasca, Iulia Lupan, Călin Căinap, Claudia Burz, Alexandru Irimie
From another perspective, miRs-29a was analyzed in serum correlated with the clinical-pathological expression of colorectal tumor patients. The conclusion was that miR-29a expression was higher in patients with colorectal tumors associated with liver metastases than in nonmetastatic patients [24]. Based on specificity and sensitivity of differentiating metastatic from non-metastatic patients, serum miR-29a is a possible candidate for early detection of liver metastases in CRC. In an orthotopic mouse model of CRC, a set of genes has been identified to play a significant role in the mediation of liver metastases. The apolipoprotein B mRNA editing enzyme catalytic subunit 3G (APOBEC3G) gene was found to be overexpressed clinically in a cohort of human liver metastases and their primary colorectal tumors, suggesting that it is possible to use these genes to anticipate liver metastases. The other genes analyzed were CD133, LIPC, and S100P who were also highly overexpressed. The final data have revealed a new mechanism by which apolipoprotein B mRNA editing enzyme catalytic subunit 3G (APOBEC3G) promotes hepatic metastasis of CRC by inhibiting miR-29 mediated suppression of MMP2 [25].
Extracellular vesicles mediate the horizontal transfer of an active LINE-1 retrotransposon
Published in Journal of Extracellular Vesicles, 2019
Yumi Kawamura, Anna Sanchez Calle, Yusuke Yamamoto, Taka-Aki Sato, Takahiro Ochiya
The expression and activity of L1 elements involves a complex interplay between a variety of host cellular factors that have been shown to restrict or support their activity within a cell [33]. In line with previous reports, we have observed the upregulation of host mechanisms such as APOBEC3 proteins that are known to restrict L1 integration and limit the activity of L1 elements [39–43]. During the period of co-culture with L1-EGFP cells, cellular factors including APOBEC3 proteins could be involved in the inhibition of L1 activity in recipient cells by interacting with L1 RNA and encoded proteins. Other studies have shown that L1 RNPs accumulate in cytoplasmic stress granules and processing bodies for degradation of L1 RNA and machinery [33,36,42–44]. Alternatively, it is also plausible that de novo L1 insertions occurred in recipient cells without the expression of the EGFP reporter gene. L1 insertions may indeed occur in transcriptionally inactive sites, undergo epigenetic silencing or 5ʹ truncation during or soon after retrotransposition that render EGFP copies inactive. Defining the mechanisms that regulate the site and frequency of de novo L1 insertions in somatic cells would help to better define the prevalence and conditions accommodating L1 activity in host cells. Nonetheless, the detection of EGFP in recipient cells indicates an active L1 retrotransposition event and demonstrates the horizontal transfer of a L1 retrotransposon mediated by EVs.