The Telomeric Repeats of HHV-6A Do Not Determine the Chromosome into Which the Virus Is Integrated

Abstract

Human herpes virus 6A (HHV-6A) is able to integrate into the telomeric and subtelomeric regions of human chromosomes representing chromosomally integrated HHV-6A (ciHHV-6A). The integration starts from the right direct repeat (DR_R) region. It has been shown experimentally that perfect telomeric repeats (pTMR) in the DR_R region are required for the integration, while the absence of the imperfect telomeric repeats (impTMR) only slightly reduces the frequency of HHV-6 integration cases. The aim of this study was to determine whether telomeric repeats within DR_R may define the chromosome into which the HHV-6A integrates. We analysed 66 HHV-6A genomes obtained from public databases. Insertion and deletion patterns of DR_R regions were examined. We also compared TMR within the herpes virus DR_R and human chromosome sequences retrieved from the Telomere-to-Telomere consortium. Our results show that telomeric repeats in DR_R in circulating and ciHHV-6A have an affinity for all human chromosomes studied and thus do not define a chromosome for integration.

Keywords: HHV-6A; TMR; chromosomal integration; ciHHV-6A; telomeric repeats.

Figure 1

Schematic of the HHV-6A DR_R structure. Left and right direct repeats are marked as DR_L and DR_R, respectively; impTMR – imperfect telomeric repeats; pTMR, perfect telomeric repeats; pac1 and pac2 – sequences that are involved in the packaging of the virus genome.

Figure 2

Indels in HHV-6A clades. (a) Indels in circulating HHV-6A. (b) Indels in ciHHV-6A that are presumably integrated into 18q. (c) Indels in ciHHV-6A that are presumably integrated into 17p. (d) Indels in ciHHV-6A that are presumably integrated into 19q. The area of the right DR is highlighted in pink, insertions are shown in red, deletions are shown in blue, and ambiguous nucleotides (N, any nucleotide) are shown in grey. Open reading frames in DR_R are shown in black below.