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SV40 Virions Encode Transgenerational Epigenetic Information from Cellular Viral Chromatin

It is becoming increasingly clear that the epigenetic modification of histones plays a significant role in regulating cellular processes. In order to determine whether epigenetics also plays a role in regulating the life cycle of chromatinized DNA viruses, we have analyzed SV40 chromatin for the presence of modified histones. We found that the modified histones present at late times in wild‐type infection were organized into one of five epigenomes, each of which consisted of a specific combination of co‐localized modified histones. Derepression of early transcription with a mutant, cs1085, which does not bind T‐antigen and cannot down‐regulate early transcription resulted in significant reductions in the levels of H3K4me1, H3K4me2 and H3K9me1, while derepression with a mutant, SM, which fails to produce a repressive miRNA resulted in an increase in H3K9 methylation which was maximal for H3K9me2. Interestingly, the epigenetic changes observed in the mutant minichromosomes as well as in other variant infections could also be observed in chromatin isolated from the corresponding virions. These results indicate that viral minichromosomes utilize epigenetic modifications in their regulatory processes like cellular chromatin and that the viral chromatin is capable of transferring information epigenetically from one infection to a subsequent infection through histone modifications present in virions.