Protein synthesis and complexity

As outlined earlier, all proteins are synthesized from mRNA templates translated on the host cell ribosomes; the source of the mRNA varies between viruses. During replication virus-specific proteins are generally synthesized in ‘phases’ categorized as early and late. The virus proteins translated in infected cells before the virus begins to copy its genome are known as early proteins, and the genes that encode them are early genes. Often this set of genes and proteins is further divided into immediate early (IE) and delayed early (DE). As their name implies, IE genes are transcribed (and hence IE proteins are synthesized) immediately a virus genome is released into the cell. Transcription of IE genes is usually carried out by the cellular enzyme RNA polymerase II, and no virus proteins other than those brought in by the virion are required. Delayed early proteins are synthesized a little later, because the expression of DE genes needs the activity of the newly made IE proteins. In the same way late (L) proteins are only synthesized after both the IE and DE proteins are available in the cell. Late protein production usually coincides with the start of the virus genome replication processes, which also need both IE and DE proteins to begin. Hence viruses generally show very strict temporal control of their protein synthesis, mostly regulated at the level of transcription of their genes. Some viruses regulate protein expression differently (such as poliovirus and HIV), but although the proteins of these viruses cannot be called early or late, their synthesis is nevertheless tightly controlled.

We have mentioned the use of overlapping gene sequences, shared promoters, and multifunctional proteins as mechanisms viruses use to maximize their small coding capacity. Hepatitis C virus, poliovirus, and HIV synthesize several proteins as a single large poly- protein precursor molecule, avoiding the need for separate transcriptional or translational sequences. The individual virus proteins must be released from the polyprotein by proteolytic cleavage by an enzyme that is part of the polyprotein itself. Like cellular proteins, virus proteins may be highly processed after their synthesis, such as being cleaved or gaining small molecules as various side groups. Two very common modifications include phosphorylation (the addition of phosphate groups) and glycosylation (the addition of sugar groups). Both modifications are highly specific, targeting certain amino acids, and often the modification is essential to the correct functioning of the protein. Other virus protein modifications include myristoylation, acylation, and palmitoylation, often associated with virion envelope glycoproteins and potentially important in the targeting of these proteins to specific sites in the cell plasma membrane before virus budding.