Publikationsdatenbank

Viral Proteins U41 and U70 of Human Herpesvirus 6A Are Dispensable for Telomere Integration (2018)

Art

Zeitschriftenartikel / wissenschaftlicher Beitrag

Autoren

Wight, Darren J (WE 5)

Wallaschek, Nina

Sanyal, Anirban (WE 5)

Weller, Sandra K

Flamand, Louis

Kaufer, Benedikt B (WE 5)

Quelle

Viruses

Bandzählung: 10

Heftzählung: 11

Seiten: e656

ISSN: 1999-4915

Sprache

Englisch

Verweise

DOI: 10.3390/v10110656

Pubmed: 30469324

Kontakt

Institut für Virologie

Robert-von-Ostertag-Str. 7-13
14163 Berlin
+49 30 838 51833
virologie@vetmed.fu-berlin.de

Abstract / Zusammenfassung

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.