Analysis of Pichinde arenavirus transcription and replication in human THP-1 monocytic cells

Human promonocytic THP-1 cells were previously shown to be nonpermissive for Pichinde virus (PV) replication unless the cells were induced to differentiate to macrophages by stimulation with phorbol ester (PMA) (J. Virol. 65, 3575, 1991). The restriction did not involve receptor modulation, virus binding, nor internalization of virus but a requirement for a host cell function in PV replication was observed in that the phorbol ester effect required protein kinase C activation and was inhibited by actinomycin D. In this report we demonstrate that PV S RNA genomes, antigenomes, GPC mRNA and NP mRNA are expressed at high levels in PMA treated THP-1 cells but at significantly lower levels or not at all in untreated cells. We have also determined that degradation of input viral S RNA does not account for decreased PV RNA synthesis in the undifferentiated cells. This suggests that the restriction of PV replication in THP-1 cells is a post-penetration event which precedes transcription of viral mRNAs and replication of viral genomes and supports a role for differentiation-specific host cell factors early in PV replication.