Mapping the telomere integrated genome of human herpesvirus 6A and 6B

• HHV-6B integrates in telomeres during latency.
• The left end of both HHV-6A and HHV-6B is joined by telomere repeats.
• A single viral genome integrates in telomeres.
• Histone deacetylase Trichostatin A induces circularization/catenation of the integrated viral genome.

Human herpesvirus 6B (HHV-6B) is the causative agent of roseola infantum. HHV-6A and 6B can reactivate in immunosuppressed individuals and are linked with severe inflammatory response, organ rejection and central nervous system diseases. About 0.85% of the US and UK population carries an integrated HHV-6 genome in all nucleated cells through germline transmission. We have previously reported that the HHV-6A genome integrated in telomeres of patients suffering from neurological dysfunction and also in telomeres of tissue culture cells. We now report that HHV-6B also integrates in telomeres during latency. Detailed mapping of the integrated viral genomes demonstrates that a single HHV-6 genome integrates and telomere repeats join the left end of the integrated viral genome. When HEK-293 cells carrying integrated HHV-6A were exposed to the histone deacetylase inhibitor Trichostatin A, circularization and/or formation of concatamers were detected and this assay could be used to distinguish between lytic replication and latency.