2. Lytic development is controlled by a cascade

11.2 Lytic development is controlled by a cascade


Phage genomes of necessity are small. As with all viruses, they are restricted by the need to package the nucleic acid within the protein coat. This limitation dictates many of the viral strategies for reproduction. Typically a virus takes over the apparatus of the host cell, which then replicates and expresses phage genes instead of the bacterial genes.


Usually the phage includes genes whose function is to ensure preferential replication of phage DNA. These genes are concerned with the initiation of replication and may even include a new DNA polymerase. Changes are introduced in the capacity of the host cell to engage in transcription. They involve replacing the RNA polymerase or modifying its capacity for initiation or termination. The result is always the same: phage mRNAs are preferentially transcribed. So far as protein synthesis is concerned, usually the phage is content to use the host apparatus, redirecting its activities principally by replacing bacterial mRNA with phage mRNA.




Figure 11.3 Lytic development takes place by producing phage genomes and protein particles that are assembled into progeny phages.

Lytic development is accomplished by a pathway in which the phage genes are expressed in a particular order. This ensures that the right amount of each component is present at the appropriate time. The cycle can be divided into the two general parts illustrated in Figure 11.3:



  • Early infection describes the period from entry of the DNA to the start of its replication.
  • Late infection defines the period from the start of replication to the final step of lysing the bacterial cell to release progeny phage particles.

The early phase is devoted to the production of enzymes involved in the reproduction of DNA. These include the enzymes concerned with DNA synthesis, recombination, and sometimes modification. Their activities cause a pool of phage genomes to accumulate. In this pool, genomes are continually replicating and recombining, so that the events of a single lytic cycle concern a population of phage genomes.


During the late phase, the protein components of the phage particle are synthesized. Often many different proteins are needed to make up head and tail structures, so the largest part of the phage genome consists of late functions. In addition to the structural proteins, "assembly proteins" are needed to help construct the particle, although they are not themselves incorporated into it. By the time the structural components are assembling into heads and tails, replication of DNA has reached its maximum rate. The genomes then are inserted into the empty protein heads, tails are added, and the host cell is lysed to allow release of new viral particles.


The organization of the phage genetic map often reflects the sequence of lytic development. The concept of the operon is taken to somewhat of an extreme, in which the genes coding for proteins with related functions are clustered to allow their control with the maximum economy. This allows the pathway of lytic development to be controlled with a small number of regulatory switches.




Figure 11.4 Phage lytic development proceeds by a regulatory cascade, in which a gene product at each stage is needed for expression of the genes at the next stage.

The lytic cycle is under positive control, so that each group of phage genes can be expressed only when an appropriate signal is given. Figure 11.4 shows that the regulatory genes function in a cascade, in which a gene expressed at one stage is necessary for synthesis of the genes that are expressed at the next stage. So at every stage of expression, one or more of the active genes is a regulator that is needed for the subsequent stage. The regulator may take the form of a new RNA polymerase, a sigma factor that redirects the specificity of the host RNA polymerase (see 9 Transcription), or an antitermination factor that allows it to read a new group of genes (see 10 The operon).


The first stage of gene expression necessarily relies on the transcription apparatus of the host cell. Usually only a few genes are expressed at this stage. Their promoters are indistinguishable from those of host genes. The name of this class of genes depends on the phage. In most cases, they are known as the early genes. In phage lambda, they are given the evocative description of immediate early. Irrespective of the name, they constitute only a preliminary, representing just the initial part of the early period. Sometimes they are exclusively occupied with the transition to the next period. At all events, one of these genes always codes for a protein that is necessary for transcription of the next class of genes.




Figure 9.31 Switches in transcriptional specificity can be controlled at initiation or termination.
Multiple figure

This second class of genes is known variously as the delayed early or middle group. Its expression typically starts as soon as the regulator protein coded by the early gene(s) is available. Depending on the nature of the control circuit, the initial set of early genes may or may not continue to be expressed at this stage (see Figure 9.31). Often the expression of host genes is reduced. Together the two sets of early genes account for all necessary phage functions except those needed to assemble the particle coat itself and to lyse the cell.


When the replication of phage DNA begins, it is time for the late genes to be expressed. Their transcription at this stage usually is arranged by embedding a further regulator gene within the previous (delayed early or middle) set of genes. This regulator may be another antitermination factor (as in lambda) or it may be another sigma factor (as in SPO1).


A lytic infection often falls into three stages, as shown in Figure 11.4. The first stage consists of early genes transcribed by host RNA polymerase (sometimes the regulators are the only products at this stage). The second stage consists of genes transcribed under direction of the regulator produced in the first stage (most of these genes code for enzymes needed for replication of phage DNA). The final stage consists of genes for phage components, transcribed under direction of a regulator synthesized in the second stage.


The use of these successive controls, in which each set of genes contains a regulator that is necessary for expression of the next set, creates a cascade in which groups of genes are turned on (and sometimes off) at particular times. The means used to construct each phage cascade are different, but the results are similar, as the following sections show.




Genes VII
Genes VII
ISBN: B000R0CSVM
EAN: N/A
Year: 2005
Pages: 382

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