Study of structure and function relationship in HIV-1 proteins
(1997)
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- Authors
- Supervisors
- Burtonboy, Guy
- Abstract
- The past decade has been a rapid evolution of knowledge and technology in virology, both fundamental and applied. The advances in the diagnosis of viral infections and in research on the viral pathogenic mechanisms and the relationship between virus and host cells, owe much to the rapid development in the fields of immunology and molecular biology. The work we present here has evolved together with the availability of new techniques and illustrates how, starting from very practical questions on the diagnosis and the epidemiology of human immunodeficiency virus (HIV), one arrives at more fundamental questions on viral diversity and the characteristics of viral proteins. <BR> In our studies in 1990, we were interested in the epidemiology and the clinical correlates of HIV infections in Benin, where our institution has longstanding contacts with des University of Cotonou. Serological and virological studies indicated a much wider diversity of HIV-1 in part of Africa than what is seen in industrialized countries. This diversity has been further described by different groups and led to the categorization of HIV-1 in subgroups and subtypes. Our approach, which is described in the second part, was to generate monoclonal antibodies against the Gag (“group specific antigen”)-encoded proteins with the aim of better defining the antigenic structure and diversity of these conserved genome products. Through mapping of the antigenic sites recognized on the HIV-1 protein Cap24 (the major capsid protein) we were able to describe a previously unrecognized epitope and to identify one monoclonal against a putative conformational epitope. The availability of monoclonals allowed us to go beyond the purely descriptive and to investigate the structure-function relationships, particularly with the anti-nucleocapsid (NCp15 and NCp7) mAbs. These functional studies led us to the third part of our work, where we applied recombinant technology to produce and characterize regulatory proteins of HIV-1. The interaction of these proteins with cellular elements could thus be studied, with particular attention for Nef, whose role is still debated, but which seems to be essential for disease progression. Finally, difficulties in the production of recombinant Vpr led us to investigate its role in the inhibition of cell growth
- Affiliations
Citations
Bodéus, M. (1997). Study of structure and function relationship in HIV-1 proteins. https://hdl.handle.net/2078.5/111434