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

• 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-1alpha, and MIP-1beta 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.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Mikrobiologi inom det medicinska området (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Microbiology in the medical area (hsv//eng)

Nyckelord

Chemokine CCL3

biosynthesis

immunology

Chemokine CCL4

biosynthesis

immunology

Cholera Toxin

pharmacology

CpG Islands

Cytokines

immunology

Enzyme-Linked Immunosorbent Assay

Flow Cytometry

HIV

drug effects

physiology

HIV Core Protein p24

analysis

immunology

HIV Infections

drug therapy

immunology

virology

HIV-1

drug effects

physiology

HIV-2

drug effects

physiology

Humans

Immunoconjugates

immunology

pharmacology

Leukocytes

Mononuclear

virology

Oligonucleotides

genetics

immunology

pharmacology

Receptors

CCR5

biosynthesis

metabolism

Receptors

CXCR4

biosynthesis

immunology

Virus Replication

drug effects

chemokines

CTB

CpG

antivirals

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