INTEGRATION OF MULTIPLE CHICKEN RETROVIRUSES INTO MULTIPLE CHICKEN HERPESVIRUSES - HERPESVIRAL GD AS A COMMON TARGET OF INTEGRATION

Integration of two different avian retroviruses, reticuloendotheliosis virus (REV) and avian leukosis virus (ALV), into the genome of two di fferent avian herpesviruses, the herpesvirus of turkeys (HVT) and Mare k's disease virus (MDV), was investigated. Integration events occurred by the fourth and sixth in vitro passage of cells coinfected with REV /HVT and ALV/MDV, respectively. In order to further characterize the i ntegration events, integrated proviruses and surrounding herpesviral g enetic material were cloned and analyzed. In the REV/HVT coinfection e xperiment, one of the three unique integrated proviruses was found to have integrated into the HVT go gene, resulting in disruption of the c oding region of this gene. The two additional unique integrations were localized to the U-L and lR(L) border regions of HVT, two previously described common sites of REV integration into MDV. interestingly, one of the integrated proviruses in the HVT genome appeared to be full le ngth, was infectious when transfected into CEF cells, and therefore co uld potentially function to produce infectious REV from an HVT infecti ous platform. In the ALV/MDV coinfection experiment, one of two unique integrated proviruses was found to have integrated into the go gene, resulting in disruption of the coding region of this gene. The second unique integration site was in the polyadenylation site of the SORF(2) gene at the boundary of the IR(s) and U-s, once again a common site o f REV integration into MDV. These results demonstrate that the U/IR-TR border regions of herpesviruses are common sites of retroviral integr ation. In addition go, in the U-s region of the herpesvirus, is a comm on site of retroviral integration in multiple herpesvirus, indicating a possible selective advantage for disruption of this gene in the in v itro growth of a herpesvirus. Finally, this is the first instance of a full-length provirus found integrated into a herpesvirus genome, indi cating that a retrovirus could alter its route of infection by being c arried in a herpesvirus genome. (C) 1994 Academic Press, Inc.