Viral Proteins U41 and U70 of Human Herpesvirus 6A Are Dispensable for Telomere Integration

Viruses. 2018 Nov 21;10(11):656. doi: 10.3390/v10110656.


Human herpesvirus-6A and -6B (HHV-6A and -6B) are two closely related betaherpesviruses that infect humans. Upon primary infection they establish a life-long infection termed latency, where the virus genome is integrated into the telomeres of latently infected cells. Intriguingly, HHV-6A/B can integrate into germ cells, leading to individuals with inherited chromosomally-integrated HHV-6 (iciHHV-6), who have the HHV-6 genome in every cell. It is known that telomeric repeats flanking the virus genome are essential for integration; however, the protein factors mediating integration remain enigmatic. We have previously shown that the putative viral integrase U94 is not essential for telomere integration; thus, we set out to assess the contribution of potential viral recombination proteins U41 and U70 towards integration. We could show that U70 enhances dsDNA break repair via a homology-directed mechanism using a reporter cell line. We then engineered cells to produce shRNAs targeting both U41 and U70 to inhibit their expression during infection. Using these cells in our HHV-6A in vitro integration assay, we could show that U41/U70 were dispensable for telomere integration. Furthermore, additional inhibition of the cellular recombinase Rad51 suggested that it was also not essential, indicating that other cellular and/or viral factors must mediate telomere integration.

Keywords: HHV-6A; human herpesvirus 6A; latency; recombination; telomere integration.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line
  • Gene Silencing
  • Herpesvirus 6, Human / physiology*
  • Humans
  • Telomere / virology*
  • Viral Proteins / genetics
  • Viral Proteins / metabolism*
  • Virus Integration*


  • Viral Proteins