Viral Proteins U41 and U70 of Human Herpesvirus 6A Are Dispensable for Telomere Integration
AbstractHuman 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. View Full-Text
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Wight, D.J.; Wallaschek, N.; Sanyal, A.; Weller, S.K.; Flamand, L.; Kaufer, B.B. Viral Proteins U41 and U70 of Human Herpesvirus 6A Are Dispensable for Telomere Integration. Viruses 2018, 10, 656.
Wight DJ, Wallaschek N, Sanyal A, Weller SK, Flamand L, Kaufer BB. Viral Proteins U41 and U70 of Human Herpesvirus 6A Are Dispensable for Telomere Integration. Viruses. 2018; 10(11):656.Chicago/Turabian Style
Wight, Darren J.; Wallaschek, Nina; Sanyal, Anirban; Weller, Sandra K.; Flamand, Louis; Kaufer, Benedikt B. 2018. "Viral Proteins U41 and U70 of Human Herpesvirus 6A Are Dispensable for Telomere Integration." Viruses 10, no. 11: 656.
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