Fig. 2. Viral transcription and replication strategies. dsDNA viruses: dsDNA virus early mRNAs are transcribed from separate promoters (two such transcripts are shown, →). The mRNA is translated in the cytoplasm and the proteins are returned to the nucleus. Replication involves binding of early-produced transcriptases ( ) to the genome; new DNA strands (-) are synthesized by semiconservative strand displacement (as illustrated) or discontinuous mechanisms. Late transcription follows DNA replication and involves transcription of mRNAs encoding structural proteins. Positive-sense RNA viruses: the positive-stranded RNA genome is directly translated by host ribosomes, producing the proteins needed for replication. Transcription of the nascent positive-sense RNA by genome-encoded RNA-dependent RNA transcriptase produces a negative-sense RNA, which serves as a template for synthesis of new genomes. Negative-sense RNA viruses: Negative-sense RNA viruses carry an RNA-dependent RNA polymerase (·) in the virus particle, which transcribes the negative sense genome (-) into positive-sense molecules. These are translated into the proteins needed for replication and encapsidation. The positive-sense molecules also serve as templates for generation of new negative-stranded genomes. Retroviruses: Retroviruses carry reverse transcriptase, which converts the single-stranded RNA genome into a circular, double-stranded DNA proviral molecule. Transcription of the first strand of DNA is initiated at the tRNA primer ( ); circularization of the RNA allows transcription to proceed along the length of the RNA strand. The genomic RNA is degraded by the RNAse property of reverse transcriptase, and the second DNA strand is synthesized using the first DNA strand as a template. The fully dsDNA circular molecule integrates into host chromosomal DNA; host DNA flanking sequences are indicated by the broken lines. Replication involves transcription of mRNAs encoding viral proteins and transcription of full-length, positive-sense RNA from the integrated provirus. (Stroop WG: Fundamentals of neurotropic viruses. In McKendall RR, Stroop WG [eds]: Handbook of Neurovirology, p 8. New York, Marcel Dekker, 1994.)