Fine mapping of an apparently targeted latent human herpesvirus type 6 integration site in chromosome band 17p13.3

An unusually high level of latent HHV-6 infection has been documented in th e peripheral blood and/or bone marrow cells of a small group of patients wi th 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 mult iple sclerosis, a specific target site for latent integration of the full-l ength 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 ma p more precisely the location of the viral integration site in one of those patients, relative to two known oncogenes mapped previously, namely CRK, a nd 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 m ap close to or within the telomeric sequences of 17p. This finding is signi ficant given that human telomeric-like repeats flank the terminal ends of t he HHV-6 genome. Cytogenetic studies showed evidence of karyotype instabili ty in the peripheral blood cells infected latently. J. Med. Virol. 58:69-75 , 1999. (C) 1999 Wiley-Liss, Inc.