A large scale whole genome sequencing study sheds light on HHV-6 integration events

Over many millennia, viral and bacterial organisms have “invaded” and altered the human genome. Bacteria produced mitochondria, and mitochondrial DNA. Viruses, too, have infected germ cells and left viral DNA remnants in human genomes. Indeed, endogenous retroviruses constitute 8% of human DNA. Human herpesvirus-6A and -6B also have integrated their DNA into human germ cells on multiple occasions in human and hominin history.

In a study led by Nicholas Parrish, 3,332 high coverage WGS datasets (including the 1,000 Genomes project and the Human Genome Diversity Project) were studied for virus-derived variation. After endogenous retroviral sequences, the most common viral DNA was from inherited chromosomally integrated HHV-6 (iciHHV-6).

Four previously unreported full-length endogenous HHV-6 sequences were also found, as independent integrations into 17p, the chromosome with the shortest telomere. In addition, the group found an instance of endogenization that included not the full HHV-6 genome but just a fusion of the two direct repeat (DR) regions at either end of the viral DNA: a solo-DR form of integrated HHV-6. The finding of solo-DR sequences provides support for the theory that viral reactivation is preceded by recombination and excision of HHV-6 from the chromosome. Endogenization of partial HHV-6 sequences has been noted previously by Ruth Jarrett (Zhang 2016) and by other investigators.

As have others, this report finds that some iciHHV-6 endogenous sequences have some similarity to circulating clades of exogenous HHV-6. In summary, this report expands our knowledge of iciHHV-6. 

Read the full article: Kojima 2021