Evidence that developmentally regulated control of gene expression by a parvoviral allotropic determinant is particle mediated

Abstract

An infectious molecular clone of the immunosuppressive strain of the autonomous parvovirus minute virus of mice [MVM(i)] was constructed deriving left-hand terminal sequences from a rare encapsidated plus strand. Progeny virus was shown to package the same proportions of plus and minus strands as did authentic MVM(i) virions. Rescue of virus from this clone also resulted in the repair of a 21-base truncation at the junction between the right-hand end of the viral insert and the vector and generated the same heterogeneous 5' end as is present in standard MVM(i) DNA. Progeny virus rescued by transfection of this clone into mouse cell lines displayed the lymphotropic phenotype characteristic of the parental MVM(i) virus from which it was derived. However, analysis of viral RNA from transfected mouse fibroblasts revealed that the MVM(i) and MVM(p) genomic clones are transcribed at the same low level. Furthermore, transfected fibroblasts yielded similar numbers of infectious centers regardless of which MVM clone was introduced. These results contrast markedly with the different infectivities of MVM(i) and MVM(p) particles and with the observation that viral transcription in fibroblasts productively infected with MVM(p) virions is 100-fold greater than that seen in the restrictive MVM(i) particle-mediated infection. These results suggest that the developmentally regulated intracellular factors controlling host cell susceptibility at the level of viral transcription interact with a component of the incoming viral capsid, rather than with a sequence within the viral DNA.