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The frequent targeting of Gag and the contrasting lack of responses to Vif, Vpu, Rev, Tat and envelope also correlate with observations from clade B CD4+ T cell epitope mapping [20].
The reason for the frequent targeting of Gag by CD4+ T cells and the link with control of viremia, could be associated with the high number of Gag molecules (1500 molecules of Gag and 100 of the precursor Gag-Pol molecules in a single immature virus particle), coupled with a relatively high degree of conservancy of this protein [32], [33].
The frequent targeting of microcephaly genes by selection also raises important questions about the functional effects of substitutions in these loci.
In addition, loss of chromosome 9 is frequent, targeting CDKN2A at 9p21 (encoding the cell cycle regulator p16INK4A and the activator of p53 p14and) and various genes on 9q, such as TSC1 (an inhibitor of mTOR).
A scenario that may explain frequent targeting of the DAPK1 promoter by aberrant DNA methylation is the aberrant recruitment of DNA methyltransferase activity to the DAPK1 promoter by oncogenic proteins (Brenner et al., 2005, Di Croce et al., 2002).
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