Broad-Spectrum Drugs Against Viral Agents
Abstract
:1. Introduction
2. TLR3 agonists: dsRNA
2.1. Poly (ICLC) as prophylaxis
2.2. Poly (ICLC) as an adjuvant
2.3. Poly (ICLC) safety
3. TLR9 agonists: CpG ODNs
3.1. CpG ODN as prophylaxis
3.2. CpG ODN as an adjuvant
3.3 CpG ODN safety
4. TLR7 agonists
5. Influenza A H5N1: cytokine response
6. Influenza A H5N1: use of non-specific immune stimulators
6. Conclusions
References
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Species | Motif | Reference |
---|---|---|
Rodents | 5′ PuPuCGPyPy 3′ | [82, 83] |
Canines | 5′ ATCGAT 3′ | [84] |
Primates | 5′ GTCGTT 3′ | [82, 85, 86] |
Type | Features | Comments |
---|---|---|
D-type (CpG- A)
| - mixed phosphodiester / phosphorothioate backbone
- 1–2 CpG dinucleotides in a central phosphodiester region flanked on both the 5′ and 3′ ends with phosphorothioate nucleotides - CpG motif is located within a palindromic sequence - run of G’s at 3′ end [88, 93] | - stimulate NK cells to produce IFN-γ [13, 88, 93]
- stimulate pDCs to produce large amounts of IFN-α, IFN-β and TNF-α [13, 88, 93, 94] - stimulate IFN-α and IFN-γ secretion and maturation of human DCs in vitro [100] - induce IFN-α within the first 12 h with considerable amounts still produced at 24–48 h [93] - indirectly activate monocytes to differentiate into myeloid DCs and produce chemokines (IL-10) [88] - trigger the maturation of APCs [88] - do not stimulate B-cells or other subsets of DCs [89] - active in mice [89], nonhuman primates [100] - best activity in humans [13, 88, 93] |
K-type (CpG- B)
| - phosphorothioate backbone
- multiple TCGT/A motifs[88, 89] | - stimulate strong B-cell and NK cell activation [13]
- activate pDCs to produce IFN-α, -β, IL-6, -8, TNF-α and IP-10 but very little IFN-γ [89, 93, 101] - IFN-α induction is relatively low and limited to the first 12 h [93] - short-lived induction of IFN-γ, IL-6 and TNF-α in BALB/c mice but IL-12 remains elevated for at least 8 d [101] - stimulate B-cells to secrete IL-6, IL-10 and IgM [88, 89, 102] - stimulate cytokine production [13] - induce cell proliferation and IL-6 production from human PBMCs [100] - active in mice [89], human PBMC in vitro [100] - poorly active in primates [89] |
C-type (CpG- C) | - phosphorothioate backbone
- palindromic sequence - no poly(G) stretch - TCGTCG at the 5′ end - frequently contains a K-type motif (GTCGTT) [13, 88] | - stimulate strong B-cell and NK cell activation [13]
- stimulate pDCs to produce IFN-α [13, 88] - potent Th1 adjuvant [13] - stimulate B-cells to secrete IL-6, IL-10 and IgM [88, 89, 102] |
© 2008 by MDPI This article is an open-access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/3.0/).
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Christopher, M.E.; Wong, J.P. Broad-Spectrum Drugs Against Viral Agents. Int. J. Mol. Sci. 2008, 9, 1561-1594. https://doi.org/10.3390/ijms9091561
Christopher ME, Wong JP. Broad-Spectrum Drugs Against Viral Agents. International Journal of Molecular Sciences. 2008; 9(9):1561-1594. https://doi.org/10.3390/ijms9091561
Chicago/Turabian StyleChristopher, Mary E., and Jonathan P. Wong. 2008. "Broad-Spectrum Drugs Against Viral Agents" International Journal of Molecular Sciences 9, no. 9: 1561-1594. https://doi.org/10.3390/ijms9091561