Inhibition of viral multiplication in cells chronically infected with mouse hepatitis virus by antisense RNA against the polymerase gene

Recently, we showed that the antisense RNA containing a hammerhead ribozyme sequence against the polymerase gene of mouse hepatitis virus (MHV) inhibited viral multiplication in acute infection [10]. In the present study, we examined the inhibitory effects of an antisense RNA on viral multiplication in chronic MHV infection. In cell line LR-2, in which the 926-nucleotide (nt) antisense RNA containing a ribozyme sequence against the polymerase gene was expressed constitutively at a high level, chronic MHV infection was established through the maintenance of infection over 100 days postinfection (d.p.i.). After 200 d.p.i., no infectious progeny virus was observed in the culture medium of chronically MHV infected LR-2 cells. Our present results showed that the anitsense RNA could also inhibit viral multiplication in chronic MHV infection.