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Published on: November 3, 2013
Fine mapping of an apparently targeted latent human herpesvirus type 6 integration site in chromosome band 17p13.3
C Morris1, M Luppi, M McDonald
1Department of Pathology, Christchurch School of Medicine, New Zealand.
Abstract:
An unusually high level of latent HHV-6 infection has been documented in the peripheral blood and/or bone marrow cells of a small group of patients with predominantly malignant lymphoid disorders, and in at least one healthy individual. We have shown previously in peripheral blood mononuclear cells (PBMCs) of three patients, two with a history of lymphoma and one with multiple sclerosis, a specific target site for latent integration of the full-length HHV-6 viral genome on the distal short arm of chromosome 17, in band p13.3. Fluorescence in situ hybridization (FISH) procedures were used to map more precisely the location of the viral integration site in one of those patients, relative to two known oncogenes mapped previously, namely CRK, and the more telomeric ABR oncogene. It is shown that the HHV-6 integration site is located at least 1,000 kb telomeric of ABR, and is very likely to map close to or within the telomeric sequences of 17p. This finding is significant given that human telomeric-like repeats flank the terminal ends of the HHV-6 genome. Cytogenetic studies showed evidence of karyotype instability in the peripheral blood cells infected latently.
Insights
Human herpesvirus 6 (HHV-6) can integrate into human chromosome 17p13.3, near telomeric sequences. This latent HHV-6 integration is linked to karyotype instability in peripheral blood cells.
Area of Science:
- Genetics
- Virology
- Oncology
Background:
- Latent Human Herpesvirus 6 (HHV-6) infections are found in patients with lymphoid disorders.
- Previous studies identified a specific integration site for HHV-6 in chromosome 17p13.3.
Purpose of the Study:
- To precisely map the HHV-6 viral genome integration site on chromosome 17.
- To investigate the relationship between the HHV-6 integration site and known oncogenes.
- To assess the impact of latent HHV-6 infection on cellular karyotype.
Main Methods:
- Fluorescence in situ hybridization (FISH) was used to map the viral integration site.
- Comparison of the HHV-6 integration site with the locations of CRK and ABR oncogenes.
- Cytogenetic analysis of peripheral blood cells with latent HHV-6 infection.
Main Results:
- The HHV-6 integration site is located at least 1,000 kb telomeric to the ABR oncogene.
- The integration site is likely near or within the telomeric sequences of chromosome 17p.
- Cytogenetic studies revealed karyotype instability in latently infected peripheral blood cells.
Conclusions:
- HHV-6 integration occurs in a specific region of chromosome 17p, adjacent to telomeric repeats.
- Latent HHV-6 infection is associated with genomic instability.
- Further research is needed to understand the implications of HHV-6 integration in lymphoid disorders.
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