Possible HIV Knockout?
Group B: Ana Rita Domingues, Nicholas Gauthier, Ilka Hoof, Eleonora Kulberkyte, and Nicolas Rapin Immunological Bioinformatics, June 2006
Acquired immunodeficiency syndrome (AIDS) is one of the worst diseases affecting mankind today. Since it was discovered in 1981, AIDS has become a major pandemic, and has killed approximately 16.3 million people. AIDS is caused by HIV (human immunodeficiency virus) and is spread by sexual contact, infected blood, and can be passed from mother to infant. It is estimated that more than 34 million people are infected worldwide, most of which are in Sub-Saharan Africa and South/Southeast Asia Figure 1: Diagram of HIV with proteins . [1,2]. HIV is a retrovirus, which means it carries its genetic information in the form of RNA and replicates via a DNA intermediate. HIV infects the components of the human immune system such as CD4+ T-cells, dendritic cells and macrophages. Much scientific research has been done to find a treatment/vaccine for HIV. The most common therapies used today are antiretroviral drugs that either interfere with reverse transcription or inhibit the viral protease . Finding a vaccine is a difficult task as HIV mutates frequently and the infection can remain latent for long periods before causing AIDS. This poster aims to present an in silico approach to developing a vaccine for HIV. We have chosen several epitopes from HIV-1 that are predicted to trigger Bcell and T-cell responses. The proteins we focused on were gp120, a surface protein that is involved in the binding of virus to the host cell, and gag, a structural protein from the virus core. The polyprotein gag is cleaved into several sub-proteins of which p24 and p17 are the largest in size.
The C-terminal cleavage probability is predicted to be high (see Fig. 3 below) for all MHC class I epitopes, with only one of them containing a strong internal cleavage site.
Figure 3: Epitope Atlas of the polytope...
References:  - Immunobiology. Janeway, C. et al, Garland Publishing, 2001;  - Immunology. Goldsby, R. et al, W.H.Freeman and Company, 2003;  - http://en.wikipedia.org/wiki/HIV  - An integrative approach to CTL epitope prediction. A combined algorithm integrating MHC-I binding, TAP transport efficiency, and proteasomal cleavage predictions. Larsen M.V., Lundegaard C., Kasper Lamberth, Buus S,. Brunak S., Lund O., and Nielsen M. European Journal of Immunology. 35(8): 2295-303. 2005  - Nine major HLA class I supertypes account for the vast preponderance of HLA-A and -B polymorphism. Sette, A., and J. Sidney. 1999. Immunogenetics 50:201-212.  - http://hiv-web.lanl.gov  - Improved prediction of MHC class I and class II epitopes using a novel Gibbs sampling approach. Nielsen M, Lundegaard C, Worning P, Hvid CS, Lamberth K, Buus S, Brunak S, Lund O. Bioinformatics. 2004 20:1388-97  - Prediction of discontinuous antibody binding epitopes in proteins. Pernille H. Andersen, Morten Nielsen and Ole Lund 2006, submitted  - CPHmodels 2.0: X3M a Computer Program to Extract 3D Models. O. Lund, M. Nielsen, C. Lundegaard, P. Worning.. Abstract at the CASP5 conferenceA102, 2002.
Figure 2: 3D-structure of HIV-1 p24 and p17 structural proteins. The four predicted MHC class I epitopes are highlighted by overall conservation. Note that the two epitopes in p17 overlap.
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