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bioRxiv · 10.1101/514075

Modulation and recruitment of TRF2 at viral telomeres during human herpesvirus 6A/B infection

Gilbert-Girard, S.·Gravel, A.·Collin, V.·Wight, D. J.·Kaufer, B. B.·Lazzerini, E.·Flamand, L.
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Abstract

Human herpesviruses 6A and 6B (HHV-6A/B) can integrate their genomes into the telomeres of host chromosomes. The HHV-6A/B genomes contain telomeric repeats essential for integration. Whether HHV-6A/B infections impact telomere homeostasis remains to be studied. We report that during infection, a massive increase in telomeric signals is observed. Such telomeric signals are detected in viral replication compartments (VRC) that colocalize with the viral IE2 and P41 proteins. Infection with HHV-6A mutants lacking telomeric repeats did not reproduce this phenotype. HHV-6A/B infections lead to increased expression of three shelterin genes, TRF1, TRF2 and TPP1. TRF2 was recruited to VRC and binding to the HHV-6A/B telomeric repeats demonstrated by chromatin immunoprecipitation and ELISA. Lastly, the HHV-6A IE2 protein colocalized with shelterin proteins at telomeres during infection. In summary, HHV-6A/B infections results in an excess of telomeric repeats that stimulates the expression of shelterin genes. TRF2 binds to viral telomeres during infection and localizes with HHV-6A IE2 protein. Our results highlight a potential role for shelterin complex proteins and IE2 during infection and possibly during integration of HHV-6A/B into host chromosomes.

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Gilbert-Girard, S., Gravel, A., Collin, V., Wight, D. J., Kaufer, B. B., Lazzerini, E., Flamand, L.. 2019-01-09. Modulation and recruitment of TRF2 at viral telomeres during human herpesvirus 6A/B infection. https://doi.org/10.1101/514075

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