Viral genomes maintained extrachromosomally in hamster polyomavirus-induced lymphomas display a cell-specific replication in vitro

Abstract

Hamster polyomavirus causes lymphomas when injected into newborn Syrian hamsters. Large amounts of extrachromosomal viral genomes are accumulated in the lymphoma cells. These genomes are characterized by deletions affecting the late coding region as well as a specific part of the noncoding regulatory region. By contrast with wild-type genomes, lymphoma-associated genomes replicate in a lymphoblastoid cell line but not in a fibroblastic cell line. The deletion acts in a cis-dominant manner and is the primary determinant of this host-range effect on replication. The boundaries of the regulatory region necessary for viral DNA replication in the two cell contexts have been defined. The regulatory region can be functionally divided in two domains: one domain (distal from the origin of replication) is necessary for viral genome replication in fibroblasts, whereas the other domain (proximal to the origin of replication) is functional only in the lymphoblastoid cell context and contains the sequence specifically conserved in the lymphoma-associated genomes. This sequence harbors a motif recognized by a lymphoblastoid cell-specific trans-acting factor.