The effects of the expression of the wt and mutant hnRNP A1 on virus production ( Figure 2B ), viral protein synthesis ( Figure 4A ) and viral RNA synthesis ( Figure 5A ) correlated with each other. Furthermore, hnRNP A1DC caused not only a global inhibition of genomic RNA replication and subgenomic mRNA transcription, but also a preferential inhibition of at least two DI RNA species. These results suggest that the inhibition of MHV replication by the hnRNP A1 mutant was most likely a direct effect on viral RNA synthesis rather than an indirect effect on other aspects of cellular or viral functions. Since hnRNP A1 binds directly to the cis-acting MHV RNA sequences critical for MHV RNA transcription (Li et al., 1997) and replication (P. Huang and M.M.C.Lai, unpublished results) , it is most likely that hnRNP A1 may participate in the formation of the transcription/replication complex. Indeed, our data show that hnRNP A1 interacts directly or indirectly with the N protein and a gene 1 product, p22, both of which are probably associated with the viral transcription/replication complex (Compton et al., 1987; Wang and Zhang, 1999; Gibson Bost et al., 2000) . hnRNP A1 may participate directly in viral RNA synthesis in a similar role to that of transcription factors in DNAdependent RNA synthesis, e.g. by maintaining favorable RNA conformation for RNA synthesis. Alternatively, hnRNP A1 may modulate MHV RNA transcription or replication by participating in the processing, transport and controlling the stability of viral RNAs. It has been reported that RNA processing of retroviruses, human T-cell leukemia virus type 2 (Black et al., 1995) and HIV-1 (Black et al., 1996) , is altered by the binding of hnRNP A1 to the viral RNA regulatory elements. It is also possible that hnRNP A1 may participate in MHV RNA synthesis indirectly by affecting the production of other host cell proteins, which may, in turn, regulate MHV RNA synthesis. Since hnRNP A1 is a dose-dependent altern-ative splicing factor (Caceres et al., 1994) , even small changes in the intracellular level of hnRNP A1 can alter the splicing of other cellular proteins. Regardless of the mechanism, our study established the importance of cellular factors in viral RNA-dependent RNA synthesis.