Publikationsdatenbank

Role for the shelterin protein TRF2 in human herpesvirus 6A/B chromosomal integration (2020)

Art

Zeitschriftenartikel / wissenschaftlicher Beitrag

Autoren

Gilbert-Girard, Shella

Gravel, Annie

Collin, Vanessa

Wight, Darren J. (WE 5)

Kaufer, Benedikt B. (WE 5)

Lazzerini-Denchi, Eros

Flamand, Louis

Quelle

PLoS pathogens

Bandzählung: 16

Heftzählung: 4

Seiten: e1008496

ISSN: 1553-7374

Sprache

Englisch

Verweise

URL (Volltext): https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1008496

DOI: 10.1371/journal.ppat.1008496

Pubmed: 32320442

Kontakt

Institut für Virologie

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

Abstract / Zusammenfassung

Human herpesviruses 6A and 6B (HHV-6A/B) are unique among human herpesviruses in their ability to integrate their genome into host chromosomes. Viral integration occurs at the ends of chromosomes within the host telomeres. The ends of the HHV-6A/B genomes contain telomeric repeats that facilitate the integration process. Here, we report that productive infections are associated with a massive increase in telomeric sequences of viral origin. The majority of the viral telomeric signals can be detected within viral replication compartments (VRC) that contain the viral DNA processivity factor p41 and the viral immediate-early 2 (IE2) protein. Components of the shelterin protein complex present at telomeres, including TRF1 and TRF2 are also recruited to VRC during infection. Biochemical, immunofluorescence coupled with in situ hybridization and chromatin immunoprecipitation demonstrated the binding of TRF2 to the HHV-6A/B telomeric repeats. In addition, approximately 60% of the viral IE2 protein localize at cellular telomeres during infection. Transient knockdown of TRF2 resulted in greatly reduced (13%) localization of IE2 at cellular telomeres (p<0.0001). Lastly, TRF2 knockdown reduced HHV-6A/B integration frequency (p<0.05), while no effect was observed on the infection efficiency. Overall, our study identified that HHV-6A/B IE2 localizes to telomeres during infection and highlight the role of TRF2 in HHV-6A/B infection and chromosomal integration.