Prevalence of chromosomally integrated human herpesvirus 6 in patients with human herpesvirus 6-central nervous system dysfunction

Abstract

We identified 37 hematopoietic cell transplantation recipients with human herpesvirus 6 (HHV-6) central nervous system dysfunction and tested donor-recipient pairs for chromosomally integrated HHV-6 (ciHHV-6). One patient had ciHHV-6A with possible HHV-6A reactivation and encephalitis. There was no ciHHV-6 enrichment in this group, but larger studies are needed to determine if patients with ciHHV-6 are at increased risk for HHV-6-associated diseases or other complications.

Keywords: Central nervous system (CNS); Herpesvirus (hhv-6); Integration; Transplant.

Figure 1

Flow diagram for chromosomally integrated HHV-6 testing. Archived pre-HCT patient and donor Beta-lymphoblastoid cell lines were the primary source for ciHHV-6 testing. When unavailable, other appropriate specimens (serum or bone marrow) were used as surrogates. *Surrogate for donor sample in cases that were missing pre-HCT donor sample. These were obtained post-engraftment. ^†One patient had a HHV-6/cellular DNA ratio significantly >1, making it impossible to rule out ciHHV-6 coupled with reactivation. Abbreviations: HCT, hematopoietic cell transplantation; HHV-6, human herpesvirus 6; CNS, central nervous system; B-lymphoblastoid, Beta-lymphoblastoid; ciHHV-6, chromosomally integrated HHV-6.

Figure 2

Phylogenetic analysis of HHV-6A gB gene sequences from pre and post-HCT samples of the described patient with ciHHV-6A compared to ciHHV-6A from 4 patients at our center, the Hector-2 cell line (Bioworld Consulting Laboratories), and 9 published sequences. This figure demonstrates that the sequence of an ~900 base pair region of the HHV-6A gB gene in the discussed patient’s pre-HCT Beta-lymphoblastoid cell line and post-HCT (D+39) serum sample were identical and diverged from 14 other available sequences. Bar = number of nucleotide changes per 100 sites. The gB gene sequences of 9 HHV-6A primary or laboratory-adapted isolates were obtained from Dr Henri Agut (Paris, France), and the geographical origins were as follows: GS, United States; U1102, Uganda; SIE, Côte d’Ivoire; TAN, Congo; and 1120, E540_132, 1116, 719 and, p523, France. An additional 4 isolates were obtained from patients at the University of Washington with chromosomally integrated HHV-6: UWciHHV6_1, UWciHHV6_2, UWciHHV6_3, UWciHHV6_4. The tree was constructed from the comparison of gB gene nucleotide sequences using the free Phylogeny.fr webservice, available at http://www.phylogeny.fr/version2_cgi/index.cgi.