| The binding affinity of double-stranded RNA motifs to HIV-1 Tat protein affects transactivation and the neutralizing capacity of anti-Tat antibodies elicited after intranasal immunization. | |
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MedLine Citation:
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PMID: 15789358 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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In this study we examined the hypothesis that the binding affinity of two double-stranded (ds) RNA motifs to HIV-1 Tat protein might affect transactivation and the type of anti-Tat immune responses. Using surface plasmon resonance technology we demonstrated the capacity of the poly(A):poly(U) (pA:pU) motif to bind with high affinity to a totally synthetic Tat protein and to inhibit more efficiently the Tat/transactivation response element (TAR) RNA interaction as compared to the poly(I):poly(C) (pI:pC) motif. Furthermore, the pA:pU motif was tenfold more effective in inhibiting Tat-driven transactivation than the pI:pC motif. Following intranasal immunization of mice, both dsRNA motifs enhanced the antibody (serum and mucosal) and cellular responses to Tat. However, only the serum samples of mice immunized with Tat + pI:pC inhibited Tat-driven transactivation. The profile of serum antibody subclasses together with the secreted cytokines by Tat-stimulated splenocyte cultures indicated that both dsRNA motifs favored the induction of a balanced Th1 and Th2 immune response. The demonstration in this study that two dsRNA motifs had a marked effect on Tat/TAR RNA interaction and on the neutralizing capacity of anti-Tat specific antibody responses highlights their potential for biological applications and the importance of selecting the appropriate motif as an adjuvant for vaccine design. |
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Authors:
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Charalambos D Partidos; Johan Hoebeke; Emmanuel Moreau; Olivier Chaloin; Mélanie Tunis; Guillaume Belliard; Jean-Paul Briand; Claude Desgranges; Sylviane Muller |
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Publication Detail:
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Type: Comparative Study; Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: European journal of immunology Volume: 35 ISSN: 0014-2980 ISO Abbreviation: Eur. J. Immunol. Publication Date: 2005 May |
Date Detail:
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Created Date: 2005-05-02 Completed Date: 2005-06-28 Revised Date: 2008-11-21 |
Medline Journal Info:
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Nlm Unique ID: 1273201 Medline TA: Eur J Immunol Country: Germany |
Other Details:
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Languages: eng Pagination: 1521-9 Citation Subset: IM |
Affiliation:
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UPR 9021, Institut de Biologie Moléculaire et Cellulaire, CNRS, Strasbourg, France. H.Partidos@ibmc.u-strasbg.fr |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Administration, Intranasal Animals Antibody Specificity / immunology Enzyme-Linked Immunosorbent Assay Female Gene Products, tat / immunology, metabolism* HIV-1 / immunology, metabolism* Interferon-gamma / immunology Interleukin-2 / immunology Mice Mice, Inbred BALB C RNA, Double-Stranded / administration & dosage, immunology*, metabolism* RNA, Viral / administration & dosage, immunology, metabolism Surface Plasmon Resonance T-Lymphocytes / immunology Transcriptional Activation* tat Gene Products, Human Immunodeficiency Virus |
| Chemical | |
Reg. No./Substance:
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0/Gene Products, tat; 0/Interleukin-2; 0/RNA, Double-Stranded; 0/RNA, Viral; 0/tat Gene Products, Human Immunodeficiency Virus; 82115-62-6/Interferon-gamma |
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