Chromatin and viral integration in immunity: The challenge of silencing non-self genes

Several viruses hide in the genome of their host. To complete their replication cycle, they need to integrate in the form of a provirus and express their genes. In vertebrates, integrated viruses can be silenced by chromatin, implying that some specific mechanisms exist to detect non-self genes. The known mechanisms depend on sequence features of retroelements, but the fluctuations of virus expression suggest that other determinants also exist. Here we review the mechanisms allowing chromatin to silence integrated viruses and propose that DNA repair may help flag them as ‘non-self’ shortly after their genomic insertion.