5 Replication of Retroviruses

Abstract

I. INTRODUCTION TO THE REPLICATION CYCLE
Retroviruses are unified by the manner in which their genomes are replicated during infection. In its simplest form, replication can be envisioned as

RNA ⇒ DNA ⇒ RNA

with the first step mediated principally by a virus-coded, RNA-directed DNA polymerase (reverse transcriptase) carried in infectious particles, and the latter step mediated principally by host enzymes also responsible for expression of cellular genes.

Retroviruses commonly associate stably with the cells they infect. To perpetuate viral genes and provide a suitable template for synthesis of viral RNA, retroviral DNA generally integrates covalently into the chromosomal DNA of host cells and replicates with the host genome. Furthermore, production of virus requires the synthesis of proteins encoded in viral mRNAs. Hence, the replication cycle can be written in more complete form as

For the purposes of this chapter, it is convenient to partition the replicative cycle into two major phases: (1) the steps leading to the synthesis and integration of a complete DNA copy of viral RNA, i.e., adsorption to and penetration of the host cell, priming and polymerization of both strands of viral DNA leading to production of linear and circular forms, and linkage of viral DNA to host DNA, and (2) expression of viral genetic information, i.e., synthesis and processing of viral RNAs (both mRNAs and genomic RNA), synthesis of viral polypeptides, cleavage and modification of viral proteins, assembly of viral nucleocapsids, and budding and maturation of viral particles. The features of this scheme are considered in detail in...