3 Regulation of Initiation of Reverse Transcription of Retroviruses

Abstract

Shortly after the discovery of reverse transcriptase in 1970 by Temin (Temin and Mizutani 1970) and Baltimore (1970), its basic enzymatic properties were established (for review, see Weiss et al. 1985; Coffin 1990). Although reverse transcriptase was an unusual DNA polymerase in that it utilized both RNA and DNA as a template, many of its intrinsic properties were found to be similar to those already ascribed to the well-studied bacterial DNA polymerases. These properties included the absolute requirement for a primer to initiate DNA synthesis (Hurwitz and Leis 1972; Leis and Hurwitz 1972; Dahlberg et al. 1974). In contrast to bacterial systems where the primer is synthesized during replication, retroviruses, as well as retroelements, utilize preexisting host-encoded transfer RNAs as primers (Weiss et al. 1985). Depending on the virus, different tRNAs are used (see Table 1). The tRNA primers are encapsidated in virions through interactions with both the viral RNA (Weiss et al. 1985) and reverse transcriptase (RT) (Panet et al. 1975; Barat et al. 1989).

Annealing of the primer to viral RNA occurs in the untranslated region close to the 5′ terminus (Weiss et al. 1985) at a site referred to as the primer-binding site (PBS) (see Fig. 1). The acceptor stem of the tRNA is unwound and between 14 and 22 nucleotides (Weiss et al. 1985) form a base-paired duplex with the viral RNA. The RNA 5′ to the PBS is called U5 and the RNA 3′ to the PBS is called the leader. The presence of the...