TY - JOUR TI - Variation in human herpesvirus 6B telomeric integration, excision, and transmission between tissues and individuals AU - Wood, Michael L AU - Veal, Colin D AU - Neumann, Rita AU - Suárez, Nicolás M AU - Nichols, Jenna AU - Parker, Andrei J AU - Martin, Diana AU - Romaine, Simon PR AU - Codd, Veryan AU - Samani, Nilesh J AU - Voors, Adriaan A AU - Tomaszewski, Maciej AU - Flamand, Louis AU - Davison, Andrew J AU - Royle, Nicola J A2 - Brinkmann, Melanie M A2 - Sawyer, Sara L A2 - Kaufer, Benedikt B VL - 10 PY - 2021 DA - 2021/09/21 SP - e70452 C1 - eLife 2021;10:e70452 DO - 10.7554/eLife.70452 UR - https://doi.org/10.7554/eLife.70452 AB - Human herpesviruses 6A and 6B (HHV-6A/6B) are ubiquitous pathogens that persist lifelong in latent form and can cause severe conditions upon reactivation. They are spread by community-acquired infection of free virus (acqHHV6A/6B) and by germline transmission of inherited chromosomally integrated HHV-6A/6B (iciHHV-6A/6B) in telomeres. We exploited a hypervariable region of the HHV-6B genome to investigate the relationship between acquired and inherited virus and revealed predominantly maternal transmission of acqHHV-6B in families. Remarkably, we demonstrate that some copies of acqHHV-6B in saliva from healthy adults gained a telomere, indicative of integration and latency, and that the frequency of viral genome excision from telomeres in iciHHV-6B carriers is surprisingly high and varies between tissues. In addition, newly formed short telomeres generated by partial viral genome release are frequently lengthened, particularly in telomerase-expressing pluripotent cells. Consequently, iciHHV-6B carriers are mosaic for different iciHHV-6B structures, including circular extra-chromosomal forms that have the potential to reactivate. Finally, we show transmission of an HHV-6B strain from an iciHHV-6B mother to her non-iciHHV-6B son. Altogether, we demonstrate that iciHHV-6B can readily transition between telomere-integrated and free virus forms. KW - excision KW - integration KW - human herpesvirus 6 KW - latency KW - telomere JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -