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Naturally Occurring Alkaloids with Anti-HIV Activity
Published in Namrita Lall, 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
Published in Yashwant Pathak, Gene Delivery, 2022
Prachi Pandey, Jayvadan Patel, Samarth Kumar
Several proteins in mammalian cells function as restriction factors during infection by HIV-1 and other viruses. However, these host factors are often weakly expressed in infected cells. Simultaneous activation of the expression of restriction factors may represent an alternate strategy to stop HIV-1 replication. The Cas9-based approach has been utilized to induce the expression of the restriction factors APOBEC3G (A3G) and APOBFC3B (A3B) in human cells. They also found that using two sgRNAs had higher efficiency than single sgRNA, and both activated proteins could block Vif-deficient HIV-1 infection by inducing dC residues to dU residues (dC-to-Du) editing of HIV-1 genome [70]. However, studies on the applying of CRISPR/Cas9 technology in activating cellular host factors to inhibit HIV-1 infection are very limited.
Extracellular vesicles and chronic inflammation during HIV infection
Published in Journal of Extracellular Vesicles, 2019
Paula Soledad Pérez, María Albertina Romaniuk, Gabriel A. Duette, Zezhou Zhao, Yiyao Huang, Lorena Martin-Jaular, Kenneth W Witwer, Clotilde Théry, Matías Ostrowski
Different mechanisms have been proposed to explain the observation that EVs produced by HIV-infected cells are able to inhibit HIV infection of target cells. For instance, it has been shown that CD4+ EVs produced by a CD4 + T cell line can inhibit the infectivity of HIV particles by binding to the viral envelope protein (gp120), which would thus not be available to bind to the CD4 receptor expressed on target cells [75]. In addition, EVs can transfer antiviral effector molecules to the recipient cells, thus blocking viral infection or restricting viral propagation. Along these lines, it has been postulated that infected cells can transfer family members of the host restriction factor APOBEC3, thus conferring resistance to HIV infection to bystander uninfected T cells [76]. However, in this study, the presence of other factors in EVs that contribute to HIV inhibition cannot be ruled out. Finally, Haque et al studied the role of EVs produced by monocytic cells exposed to cigarette smoke condensate (CSC) on HIV-1 replication, showing that CSC-treated monocytes produce EVs with increased anti-HIV activity, likely due to modified incorporation of antioxidant molecules into EVs [77].
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].
Recent advances in the discovery and development of TLR ligands as novel therapeutics for chronic HBV and HIV infections
Published in Expert Opinion on Drug Discovery, 2018
Keye Du, Jia Liu, Ruth Broering, Xiaoyong Zhang, Dongliang Yang, Ulf Dittmer, Mengji Lu
Previous studies indicate that TLR ligands can suppress the replication of retroviruses both in vitro and in vivo. HIV replication can be inhibited in DC, monocytes, macrophages, and activated T cells by TLR ligand stimulation. An inhibition of HIV replication was found after the stimulation of infected cells with TLR3, −4, −7, −8, or −9 ligands. TLR7 and TLR8 were potent in reducing virus propagation in macrophages [102–104]. Several mechanisms of the antiviral activity of TLR7/8 ligands in macrophages were discovered including vitamin D-mediated autophagy [104], and MyD88-dependent IFN-α induction [103]. Also the HIV susceptibility of DCs was influenced by TLRs and C-type lectins, including TLR3 and TLR4 ligands and NOD2 [105]. HIV replication in immature DC could be fully prevented if Poly(I:C) was added immediately after virus pulsing in vitro [106]. One study analyzed the total PBMCs and found that TLR3, −7, −8, and −9 blocked HIV replication, with an involvement of the antiviral proteins APOBEC3G and SAMHD1 in virus suppression [107].