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Suppression of HIV replication in vitro by CpG and CpG conjugated to the non toxic B subunit of cholera toxin

Nowroozalizadeh, Salma LU ; Jansson, Marianne LU ; Adamsson, Jenni; Lindblad, Marianne; Fenyö, Eva Maria LU ; Holmgren, Jan and Harandi, Ali M (2008) In Current HIV Research 6(3). p.230-238
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... (More)
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-1 alpha, and MIP-1 beta 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. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
chemokines, CTB, CpG, HIV, antivirals
in
Current HIV Research
volume
6
issue
3
pages
230 - 238
publisher
Bentham Science Publishers
external identifiers
  • wos:000256616100006
  • scopus:47749130824
ISSN
1570-162X
DOI
10.2174/157016208784325038
language
English
LU publication?
yes
id
9f375707-5703-4b55-834d-b8d9165917ff (old id 1191479)
date added to LUP
2008-09-08 16:28:24
date last changed
2017-01-01 05:03:38
@article{9f375707-5703-4b55-834d-b8d9165917ff,
  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-1 alpha, and MIP-1 beta 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.},
  author       = {Nowroozalizadeh, Salma and Jansson, Marianne and Adamsson, Jenni and Lindblad, Marianne and Fenyö, Eva Maria and Holmgren, Jan and Harandi, Ali M},
  issn         = {1570-162X},
  keyword      = {chemokines,CTB,CpG,HIV,antivirals},
  language     = {eng},
  number       = {3},
  pages        = {230--238},
  publisher    = {Bentham Science Publishers},
  series       = {Current HIV Research},
  title        = {Suppression of HIV replication in vitro by CpG and CpG conjugated to the non toxic B subunit of cholera toxin},
  url          = {http://dx.doi.org/10.2174/157016208784325038},
  volume       = {6},
  year         = {2008},
}