Transcription of visna virus during its lytic cycle: evidence for a sequential early and late gene expression

Visna lentivirus persists in sheep under a restricted form. Following induction events not yet defined at the molecular level, visna virus is activated to replicate productively through a short lytic cycle, the usual expression of visna virus in tissue culture. In an attempt to understand the relationship between latency and lytic replication, we characterized the transcripts of visna virus during its lytic growth by Northern blotting and S1 mapping analyses. The viral transcription pattern is relatively complex with a sequential expression in two steps: (i) an early (24 hr postinfection) expression of two multispliced mRNAs of 1.6 and 1.2 kb, which contain sequences from the 5' end of the genome, sequences from the central part of the genome from the 3' end of pol to the 5' end of env, and 3'-terminal sequences, and (ii) a late (72 hr postinfection) expression of both small mRNAs plus that of four large mRNAs of 9.4, 4.8, 4.3, and 3.7 kb. Except for the 9.4-kb RNA which is the genomic transcript, the three other large transcripts arise by a single splicing event joining 5'-terminal sequences to sequences located at positions 3' to the pol gene. This two-step expression of early and late genes of visna virus represents a novel important feature of the replicative cycle of lentiviruses.