The HIV hide and seek game: an immunogenomic analysis of the HIV epitope repertoire.
BACKGROUND
Viruses employ various means to evade immune detection. One common evasion strategy is the removal of CD8 cytotoxic T-lymphocyte (CTL) epitopes.


METHODS
Here, we use bioinformatic tools to compute the HIV CTL epitope repertoire presented by over 8000 HIV sequences in multiple Human Leukocyte Antigen alleles. We define the 'Size of Immune Repertoire' (SIR) score, which represents the ratio between the number of the predicted epitopes within a protein and their expected number within a scrambled version of the same protein.


RESULTS
We show that HIV proteins present less epitopes than expected and that the number of epitopes gradually decreases from SIV to recent HIV sequences. The decrease of the SIR score of HIV is accompanied by a high frequency of replacement mutations within epitopes. The SIR score of the different HIV proteins is not uniform. The regulatory proteins, Tat and Rev, expressed early during cellular infection have a low SIR score, whereas virion-associated genes that are expressed later, such as Env, Pol and Gag, have a higher SIR score. Actually, the SIR score of Gag keeps increasing over time.


CONCLUSIONS
We hypothesize that our results reflect an HIV immune evasion strategy. This involves the targeting of the CTL immune response to viral structural and enzyme proteins, allowing the virus a time interval to propagate before its host cells are destroyed by CTLs. An efficient anti-HIV CTL response against HIV should thus also target the regulatory genes that HIV seeks to hide from the immune system.
Vider-Shalit
Tal
T
Math Department and Gonda Brain Research Center, Bar Ilan University, Ramat Gan, Israel.
Almani
Michal
M
Sarid
Ronit
R
Louzoun
Yoram
Y
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D000939:Epitopes / Q000235:genetics / Q000276:immunology*; D015967:Gene Expression Regulation, Viral; D006678:HIV / Q000235:genetics / Q000276:immunology*; D015658:HIV Infections / Q000235:genetics / Q000276:immunology*; D006680:HLA Antigens / Q000235:genetics / Q000276:immunology; D054298:Human Immunodeficiency Virus Proteins / Q000235:genetics / Q000276:immunology; D006801:Humans; D016097:Simian Acquired Immunodeficiency Syndrome / Q000235:genetics / Q000276:immunology*; D015302:Simian Immunodeficiency Virus / Q000235:genetics / Q000276:immunology*
D000939:Epitopes; D006680:HLA Antigens; D054298:Human Immunodeficiency Virus Proteins