Assembly of icosahedral capsids

In the majority of cases studied in detail, maturation of the icosahedral capsid from an immature procapsid to final state involves specific proteolytic cleavage of one or several capsid proteins that were assembled into the immature virus particle. This cleavage results in subtle changes in structure or increased capsid stability, and often accompanies inclusion of the viral genome. These cleavage steps, accomplished by virus-encoded proteins called maturational proteases, are quite limited — only one or a few discrete peptide bonds are hydrolyzed. Thus, a fairly good general rule has the assembly of icosahedral capsids involving both preassembly of procapsids and specific covalent modifications of the virion proteins by proteolytic processing. The high specificity of maturational proteases and the fact that they are encoded by the viral genome make them attractive targets for antiviral therapy; protease inhibitors of HIV have been found to have great therapeutic value (see Chapter 8).

Some of the general models for assembly of an icosahedral capsid were based on early studies on poliovirus, a small RNA-containing virus. One characteristic of poliovirus infection in the laboratory is the formation of empty capsids. Thus, it is clear that the viral capsomers can self-assemble. This observation was interpreted as indicating that empty capsids assemble before the genome enters the virion. Ironically, some recent studies on the assembly of poliovirus and related viruses suggested that the procapsid assembles directly around the viral RNA, and empty capsids are a nonfunctional byproduct of the assembly process. Despite this, empty capsids can form a stable structure spontaneously.

With larger icosahedral viruses, the process of capsid assembly is complex, with scaffolding proteins forming a "mold" or pattern for the final capsid. In either case, capsid assembly occurs before entry of the viral genome into the capsid, and one of the hallmarks of icosahedral virus maturation is the generation of empty capsids.

Assembly of the head of bacteriophage P22 is shown in Fig. 6.7 as an illustration of this process. The process is quite similar to the assembly of herpesvirus capsids. Note, the pilot proteins, which are important for injection of the genome (see Fig. 6.4), may also help the capsid proteins assemble. The scaffolding proteins can recycle and function in the assembly of

Fig. 6.7 Assembly of the phage P22 capsid and maturation by insertion of viral genomic DNA. Individual capsomer subunits preassemble into a procapsid around scaffolding protein. This latter protein is recycled with phage P22 but can be proteolytically removed with a maturational protease with other icosahedral viruses. The empty head then associates with viral genomes. Genome insertion requires both energy and a conformational change in the procapsid.

more than one capsid. Also note that the term pilot protein here has a completely different meaning than when used in the T-even bacteriophage infection discussed previously.

Retrovirus proteases "activate" virion-associated enzymes during the final stages of virion maturation following release from the infected cell. These retrovirus proteases form part of the virion's structural protein. Antiviral drugs targeting the HIV protease have shown significant therapeutic benefit, and other viral proteases are targets for drug development because they are specific to the virus encoding them. This is discussed in more detail in Chapter 20, Part IV.

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