Next Article in Journal
Platycodin D Suppresses Type 2 Porcine Reproductive and Respiratory Syndrome Virus In Primary and Established Cell Lines
Previous Article in Journal
Recombinant Lassa Virus Expressing Green Fluorescent Protein as a Tool for High-Throughput Drug Screens and Neutralizing Antibody Assays
Open AccessArticle

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

1
Institut für Virologie, Freie Universität Berlin, Robert von Ostertag-Straße 7-13, 14163 Berlin, Germany
2
Institute for Molecular Infection Biology, Julius-Maximilians-Universität Wϋrzburg, Josef-Schneider-Straße 2, 97080 Wϋrzburg, Germany
3
Molecular Biology and Biophysics, UConn Health, 263 Farmington Avenue, Farmington, CT 06030-3205, USA
4
Department of Microbiology and Immunology, CHU de Québec, Université Laval, Quebec, QC G1V 4G2, Canada
*
Authors to whom correspondence should be addressed.
Viruses 2018, 10(11), 656; https://doi.org/10.3390/v10110656
Received: 19 September 2018 / Revised: 16 November 2018 / Accepted: 17 November 2018 / Published: 21 November 2018
(This article belongs to the Section Animal Viruses)
  |  
PDF [1919 KB, uploaded 21 November 2018]
  |  

Abstract

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. View Full-Text
Keywords: human herpesvirus 6A; HHV-6A; telomere integration; latency; recombination human herpesvirus 6A; HHV-6A; telomere integration; latency; recombination
Figures

Figure 1

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

Supplementary material

SciFeed

Share & Cite This Article

MDPI and ACS Style

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.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Viruses EISSN 1999-4915 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top