Changes of methylation at enhancers appear to be essential for HIV infection progression

Background We studied the influence of the European HIV-1 subtype B (most common in the Western and central Europe) and subtype A6 (prevalent in Eastern Europe including Ukraine and Russia) on host methylome during infection progression and in virus subtype specific manner. Results Our results show that regardless of virus subtype, in the initial phase of the infection, HIV related methylation changes more frequently affect parts of the genome with low expression activity including heterochromatin and quiescent regions. But, at stage four of the infection regions of the genome harbouring HIV related methylation changes are enhancers. We further showed that the effect of each of the virus subtype on host methylome is to a large extent similar. And both virus subtypes appear to induce hypomethylation of loci associated with key pathways involved in viral infection. Nevertheless, our results also indicate that each of the virus subtype at least to some extent affects host methylome in virus subtype specific manner. Lastly, we showed that infection progression related methylation changes that we identified, are reversed with antiretroviral therapy. Conclusions: Methylation changes at the enhances appear to be key mechanisms involved in HIV-1 subtype B and A6 infection progression. Despite general uniform effect of the virus subtype on host methylome, each of the virus subtype appears also to affects host methylome in specific manner.