Reactivation of Chromosomally Integrated Human Herpesvirus-6 by Telomeric Circle Formation

More than 95% of the human population is infected with human herpesvirus-6 (hhv-6) during early childhood and maintains latent hhv-6 genomes either in an extra-chromosomal form or as a chromosomally integrated hhv-6 (cihhv-6). in addition,approximately 1% of humans are born with an inheritable form of cihhv-6 integrated into the telomeres of chromosomes. immunosuppression and stress conditions can reactivate latent hhv-6 replication,which is associated with clinical complications and even death. we have previously shown that chlamydia trachomatis infection reactivates cihhv-6 and induces the formation of extra-chromosomal viral dna in cihhv-6 cells. here,we propose a model and provide experimental evidence for the mechanism of cihhv-6 reactivation. infection with chlamydia induced a transient shortening of telomeric ends,which subsequently led to increased telomeric circle (t-circle) formation and incomplete reconstitution of circular viral genomes containing single viral direct repeat (dr). correspondingly,short t-circles containing parts of the hhv-6 dr were detected in cells from individuals with genetically inherited cihhv-6. furthermore,telomere shortening induced in the absence of chlamydia infection also caused circularization of cihhv-6,supporting a t-circle based mechanism for cihhv-6 reactivation. © 2013 prusty et al.