Tacaribe virus gene expression in cytopathic and non-cytopathic infections.

Tacaribe virus (TV) replication was compared in Vero cells infected under conditions leading either to cell death (c.p.e.(+) infection) or to the establishment of persistence (c.p.e.(-) infection). To this end, two virus preparations were employed: one containing a ratio of standard (plaque-forming) viruses to interfering particles (IP) that would induce a distinct lytic response in Vero cells infected at multiplicities giving synchronous infection and another virus stock enriched in IP that would block the cell-killing potential of the cytolytic virus stock. The following results were obtained: (1) No qualitative differences were observed in the species of intracellular viral RNAs in the lytic infection in comparison with infections leading to persistence or during the early stages of persistence. (2) Levels of viral RNAs were severely reduced when the cells were infected with IP in addition to standard viruses, the RNA accumulation being inversely proportional to the ratio of IP to standard viruses used in the infections. (3) Accumulation of the three measurable mRNAs (those corresponding to the glycoprotein precursor [GPC], to the nucleoprotein [N], and to the p11Z protein) ended earlier in the c.p.e.(-) infections (around 18 hr p.i.) than in the c.p.e.(+) infection (45-68 hr p.i.). (4) The rates of synthesis of the GPC, N, and p11Z proteins were largely determined in both the c.p.e.(+) and c.p.e.(-) infections by the amounts of their corresponding mRNAs. (5) The kinetics of accumulation of the S genomes and also the ratios of the S genome to S antigenome were similar in the different infections (accumulation ending at 45-68 hr p.i.). (6) L genome accumulation proceeded for longer time (until 92 hr p.i.) in the c.p.e.(+) infection than in the c.p.e.(-) infections. In the latter accumulation ended at around 45 hr p.i. Until this time ratios of L genome to L antigenome were similar in the different infections. It is concluded that IP affect virus mRNA synthesis early after infection reducing in this way the rate of viral protein synthesis. Low levels of viral proteins might then limit virus replication. In addition, the results support the idea that in TV infections transcription and replication are independently regulated. The implications of these results with regards to the nature and mode of action of TV IP are discussed.