Mystery: Why was ciHHV-6A integration lost with tumor formation?

Royle at confernece copyNicola Royle’s laboratory at the University of Leicester in the UK has reported that a ciHHV-6A patient with an HHV-8-negative primary effusion-like lymphoma had fully integrated genomes in the blood, but lost the integration in the tumor. Did the release of HHV-6A genomes play a role in tumor formation?

Primary effusion lymphoma (PEL) is usually associated with HHV-8 (Kaposi’s sarcoma-associated herpesvirus) infection in immunocompromised patients. Occasionally, lymphomas are found that are HHV-8 negative. In one such case, chromosomally integrated HHV-6 was found in the blood but not the tumor.

The authors propose that there may have been telomere-loop formation within the ciHHV-6 genome that was followed by excision, allowing release of the viral genome from the telomere. They state that the loss of the integrated genome could have been a coincidence, or the loss of the genome may have contributed to the development of the PEL like lymphoma via a novel mechanism, possibly by disrupting telomere function or the expression of nearby subtelomeric genes.

The patient was a 73 year-old immunocompetent woman with no prior history of infections.

For more information the full paper (Zhang 2016).