IDENTIFICATION OF HUMAN TELOMERIC REPEAT MOTIFS AT THE GENOME TERMINIOF HUMAN HERPESVIRUS-7 - STRUCTURAL-ANALYSIS AND HETEROGENEITY

Human herpesvirus 6 (HHV-6) and HHV-7 are closely related T-lymphotrop ic betaherpesviruses which share a common genomic organization and are composed of a single unique component (U) that is bounded by direct r epeats (DR(L) and DR(R)). In HHV-6, a sequences have been identified a t each end of the DR motifs, resulting in the arrangement aDR(L)a-U-aD R(R)a, In order to determine whether HHV-7 contains similar a sequence s, we have sequenced the DR(L)-U and U-DR(R) junctions of HHV-7 strain JI, together with the DR(R) . DR(L) junction from the head-to-tail co ncatamer that is generated during productive virus infection. In addit ion, we have sequenced the genomic termini of an independent isolate o f HHV-7, As in HHV-6, a (GGGTTA)(n) motif identical to the human telom eric repeat sequence (TRS) was identified adjacent to, but not at, the genome termini of HHV-7, The left genome terminus and the U-DR(R) jun ction contained a homolog of the consensus herpesvirus packaging signa l, pac-1, followed by short tandem arrays of TRSs separated by single copies of a second 6-bp repeat, This organization is similar to the ar rangement found at U-DR(R) in HHV-6 but differs from it in that the TR S arrays are considerably shorter in HHV-7. The right genome terminus and the DR(L)-U junction contained a homolog of the consensus herpesvi rus packaging signal, pac-2, followed by longer tandem arrays of TRSs separated by single copies of either a 6-bp or a 14-bp repeat. This ar rangement is considerably more complex than the simple tandem array of TRSs that is present at the corresponding genomic location in HHV-6 a nd corresponds to a site of both inter- and intrastrain heterogeneity in HHV-7. The presence of TRSs in lymphotropic herpesviruses from huma ns (HHV-6 and HHV-7), horses (equine herpesvirus 2), and birds (Marek' s disease virus) is striking and suggests that these sequences may hav e functional or structural significance.