The relationship of telomere length to HHV-6 integration

Telomere length does not appear to influence the efficiency of viral integration, and viral integration may not affect telomere length.

Since the discovery that HHV-6A/B can integrate its DNA into the telomeres of host chromosomes, somewhat varying results have been reported on the relationship between telomere length and the likelihood and efficiency of viral integration.  Does telomere length affect the likelihood or efficiency of viral integration?  And does viral integration affect the length of the telomere?

A team from the Free University of Berlin and CHU de Quebec Research Center of Laval University, in Quebec, developed techniques for measuring telomere length by quantitative fluorescence in situ hybridization, confocal microscopy and computational processing.  The method was validated on a panel of HeLa cells with telomeres of known and differing lengths, including a cell line (TZAP-KO C3) that lacks a telomere-trimming molecule.

Some previous studies had suggested that HHV-6A/B might be integrated in the shortest telomeres. The team tested that hypothesis by infecting various HeLa cell lines with a GFP reporter HHV-6A.  Maintenance of the integrated virus at 14 days was comparable across all the cell lines: telomere length did not seem to have affected the ability of the virus to stably integrate its genome into the telomere.  Nor did the absence of TZAP, the telomere-trimming molecule.

Figure – Telomeric zinc finger knock outs did not decrease viral integration at day 0 and day 14 post infection.

Did viral integration affect the length of the telomere?  While no general and persisting telomere shortening was observed, there was some evidence of transient shortening possibly followed by compensatory neo-telomere formation.

These careful in vitro studies in HeLa cell lines add to our knowledge of the relationship between telomere length and the efficiency of viral integration. How representative the results are of in vivo infection in the virus’s normal target cells is not clear.

Read the full article:  Wight 2022