Abstract
Administration of oligodeoxynucleotides (ODNs) containing CpG motifs generates a rapid and potent response of CC-chemokines, known as ligands of the HIV-1 co-receptor CCR5, in the murine female genital tract. The present study explored the potential HIV inhibitory activities of different human CpG prototypes either alone or conjugated to the non-toxic subunit of cholera toxin (CTB). Results showed that in vitro replication of both HIV-1 and HIV-2 can be suppressed by different human CpG prototypes. Importantly, the conjugation of CpG ODN to CTB (CTB-CpG) enhanced the antiviral activity of CpG against primary HIV-1 isolates of both R5 and X4 phenotypes in peripheral blood mononuclear cells (PBMC) as well as U87.CD4 co-receptor indicator cells. CTB-CpGs triggered higher amounts of MIP-1α, and MIP- 1β in PBMC than the corresponding CpG ODNs, which may explain the superior antiviral effect of CTB-CpG against R5 virus in PBMC. Incubation of PBMC with CpG ODN and CTB-CpG did not alter surface expression of HIV-1 receptors indicating that the observed anti-HIV-1 effect is not mediated through down regulation of HIV-1 receptors on target cells. Further, the enhanced antiviral effect of CTB-CpG was dependent on the presence of phosphorothioate backbone in the ODN, whereas the presence of CpG motif in ODNs was dispensable. These results have implications for the development of novel intervention strategies to prevent HIV infection.
Keywords: HIV, antivirals, CpG, CTB, chemokines
Current HIV Research
Title: Suppression of HIV Replication In Vitro by CpG and CpG Conjugated to the Non Toxic B Subunit of Cholera Toxin
Volume: 6 Issue: 3
Author(s): Salma Nowroozalizadeh, Marianne Jansson, Jenni Adamsson, Marianne Lindblad, Eva-Maria Fenyo, Jan Holmgren and Ali M. Harandi
Affiliation:
Keywords: HIV, antivirals, CpG, CTB, chemokines
Abstract: Administration of oligodeoxynucleotides (ODNs) containing CpG motifs generates a rapid and potent response of CC-chemokines, known as ligands of the HIV-1 co-receptor CCR5, in the murine female genital tract. The present study explored the potential HIV inhibitory activities of different human CpG prototypes either alone or conjugated to the non-toxic subunit of cholera toxin (CTB). Results showed that in vitro replication of both HIV-1 and HIV-2 can be suppressed by different human CpG prototypes. Importantly, the conjugation of CpG ODN to CTB (CTB-CpG) enhanced the antiviral activity of CpG against primary HIV-1 isolates of both R5 and X4 phenotypes in peripheral blood mononuclear cells (PBMC) as well as U87.CD4 co-receptor indicator cells. CTB-CpGs triggered higher amounts of MIP-1α, and MIP- 1β in PBMC than the corresponding CpG ODNs, which may explain the superior antiviral effect of CTB-CpG against R5 virus in PBMC. Incubation of PBMC with CpG ODN and CTB-CpG did not alter surface expression of HIV-1 receptors indicating that the observed anti-HIV-1 effect is not mediated through down regulation of HIV-1 receptors on target cells. Further, the enhanced antiviral effect of CTB-CpG was dependent on the presence of phosphorothioate backbone in the ODN, whereas the presence of CpG motif in ODNs was dispensable. These results have implications for the development of novel intervention strategies to prevent HIV infection.
Export Options
About this article
Cite this article as:
Nowroozalizadeh Salma, Jansson Marianne, Adamsson Jenni, Lindblad Marianne, Fenyo Eva-Maria, Holmgren Jan and Harandi M. Ali, Suppression of HIV Replication In Vitro by CpG and CpG Conjugated to the Non Toxic B Subunit of Cholera Toxin, Current HIV Research 2008; 6 (3) . https://dx.doi.org/10.2174/157016208784325038
DOI https://dx.doi.org/10.2174/157016208784325038 |
Print ISSN 1570-162X |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4251 |
Call for Papers in Thematic Issues
HIV vaccine development
The development of a safe and effective vaccine that impedes HIV-1 transmission and/or limits the severity of infection remains a public health priority. The HIV-1/AIDS pandemic continues to have a disproportionate impact on vulnerable and under-served communities in the USA and globally. In the USA, minority communities that have relatively ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
Related Articles
-
Resveratrol in Cancer: Cellular and Mitochondrial Consequences of Proton Transport Inhibition
Current Pharmaceutical Design Serotonin and Cancer: What Is the Link?
Current Molecular Medicine Strategies to Overcome Multi-Drug Resistance in Cancer Cells: the Contribution of siRNA and Nanotechnologies
Current Organic Chemistry Therapeutic Targeting of CPT-11 Induced Diarrhea: A Case for Prophylaxis
Current Drug Targets The Macrophage Stimulating Protein/Ron Pathway as a Potential Therapeutic Target to Impede Multiple Mechanisms Involved in Breast Cancer Progression
Current Drug Targets Cancer Stem Cells Equipped with Powerful Hedgehog Signaling and Better Epigenetic Memory: Avenues to Look for Cancer Therapeutics
Current Cancer Drug Targets Population-based Study of Risk Polymorphisms Associated with Vascular Disorders and Dementia
Current Genomics New Trends of Deep Learning in Clinical Cardiology
Current Bioinformatics Synthesis and Characterization of Two New Thiophene Acetyl Salicylic Acid Esters and their ortho- and para-effect on Anticancer Activity
Anti-Cancer Agents in Medicinal Chemistry MicroRNA-490-5P Targets CCND1 to Suppress Cellular Proliferation in Glioma Cells and Tissue Through Cell Cycle Arrest
Current Neurovascular Research Cytotoxic Activity of Polysubstituted 7-chloro-4-quinolinylhydrazone Derivatives
Letters in Drug Design & Discovery ETS Proteins and MMPs: Partners in Invasion and Metastasis
Medicinal Chemistry Reviews - Online (Discontinued) Endocannabinoid Signaling in Midbrain Dopamine Neurons: More than Physiology?
Current Neuropharmacology Polyisoprenylation Potentiates the Inhibition of Polyisoprenylated Methylated Protein Methyl Esterase and the Cell Degenerative Effects of Sulfonyl Fluorides
Current Cancer Drug Targets Anti-Epidermal Growth Factor Receptor Strategies to Enhance Radiation Action
Current Medicinal Chemistry - Anti-Cancer Agents Recent Advancements in Fuzzy C-means Based Techniques for Brain MRI Segmentation
Current Medical Imaging Expression of Rab3b in Human Glioma: Influence on Cell Proliferation and Apoptosis
Current Pharmaceutical Design The Non-Canonical IκB Kinases IKKε and TBK1 as Potential Targets for the Development of Novel Therapeutic Drugs
Current Molecular Medicine Therapeutic Strategies for Targeting BRAF in Human Cancer
Reviews on Recent Clinical Trials Role of Inflammatory Mediators in Angiogenesis
Current Drug Targets - Inflammation & Allergy