Highly stable oligomerization forms of HIV-1 Tat detected by monoclonal antibodies and requirement of monomeric forms for the transactivating function on the HIV-1 LTR

Details

Serval ID
serval:BIB_A908FE3742B5
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Highly stable oligomerization forms of HIV-1 Tat detected by monoclonal antibodies and requirement of monomeric forms for the transactivating function on the HIV-1 LTR
Journal
European Journal of Immunology
Author(s)
Tosi  G., Meazza  R., De Lerma Barbaro  A., D'Agostino  A., Mazza  S., Corradin  G., Albini  A., Noonan  D. M., Ferrini  S., Accolla  R. S.
ISSN
0014-2980 (Print)
Publication state
Published
Issued date
04/2000
Volume
30
Number
4
Pages
1120-6
Notes
Journal Article
Research Support, Non-U.S. Gov't --- Old month value: Apr
Abstract
The use of newly generated murine monoclonal antibodies directed against distinct epitopes of a functionally active, chemically synthesized HIV-1 Tat protein has permitted the identification of several molecular forms including monomers, dimers and trimers. Dimers and trimers are particularly stable and resistant to strong reducing conditions. Through epitope mapping it has been possible to demonstrate that the major immunodominant epitope is contained within the basic region of the Tat protein and is lost after oligomerization of the molecule. In contrast, N-terminal, C-terminal and conformation-dependent epitopes are still accessible to mAb specific recognition after Tat oligomerization. Moreover, by using a quantitative HIV-LTR transactivation assay depending upon exogenous Tat, we could extrapolate the amount of functional Tat produced by cell lines stably transfected with the viral transactivator. More importantly, we could show that only the monomeric form of exogenous Tat is the relevant functional form acting in cells harbouring the HIV-1 LTR promoter.
Keywords
Alkylation Amino Acid Sequence Antibodies, Monoclonal/*immunology/pharmacology Antibody Specificity/immunology Cell Line Dimerization Dose-Response Relationship, Drug Epitope Mapping Gene Expression Regulation, Viral/drug effects Gene Products, tat/chemical synthesis/*immunology/*metabolism/pharmacology HIV Antibodies/immunology/pharmacology HIV Long Terminal Repeat/*genetics HIV-1/*genetics Heat Humans Immunodominant Epitopes/chemistry/immunology Protein Binding/drug effects Protein Conformation/drug effects Protein Denaturation/drug effects Reducing Agents/pharmacology Solutions *Trans-Activation (Genetics)/drug effects Transfection
Pubmed
Web of science
Open Access
Yes
Create date
24/01/2008 14:55
Last modification date
20/08/2019 15:13
Usage data