Based on previous ®ndings (Kim and Makino, 1995; Zhang and Lai, 1995; Li et al., 1997) and the results from this study, we propose a model for the regulation of transcription/replication of MHV RNA by hnRNP A1. We hypothesize that hnRNP A1 is one of the components of the MHV RNA transcription or replication complex, and the crosstalk between hnRNP A1 and another viral or cellular RNA-binding protein (designated X in Figure 8 ) is essential for MHV replication and transcription. The X protein binds to the C-terminus of hnRNP A1 and cooperates with hnRNP A1 to recruit more proteins to form the transcription or replication complex. The C-terminaldeletion mutant of hnRNP A1 loses the ability to interact with the X protein and to bring it into the initiation complex, resulting in an inhibition of MHV RNA transcription and replication. The residual replication and transcription activities of MHV RNA in the absence of functional hnRNP A1 may be due to a limited af®nity of the X protein to a cis-acting signal that is only present in MHV genomic RNA (site B). On the other hand, DI RNAs may lack this cis-acting signal. When the crosstalk between the X protein and hnRNP A1 is abolished by the dominant-negative mutant of hnRNP A1, the X protein can no longer participate in the formation of the initiation complex, resulting in a complete loss of DI RNA replication.