Particles

This chapter considers why viruses make particles to contain their genomes. In order to understand how virus particles are put together, it explains how symmetry allows particles to assemble using only the information contained within the particle. It finishes by looking at the main types of virus particle—helical and icosahedral—as well as more complex structures and considers how the virus coat interacts with the host cell.

Keywords

Capsids; coat proteins; genome packaging; particles; symmetry; virions

Contents

Intended Learning Outcomes

On completing this chapter you should be able to:

The Function and Formation of Virus Particles

Figure 2.1 shows an illustration of the approximate shapes and sizes of different families of viruses. Virus particles may range in size by nearly 100-fold, from around 17 nm (Porcine circovirus) to 1,200 nm in length (Pithovirus sibericum). The protein subunits in a virus capsid are redundant, that is, there are many copies in each particle. Damage to one or more capsid subunits may make that particular subunit nonfunctional, but rarely does limited damage destroy the infectivity of the entire particle. This helps make the capsid an effective barrier. The protein shells surrounding virus particles are very tough, about as strong as a hard plastic such as Perspex or Plexiglas, although they are only a billionth of a meter or so in diameter. They are also elastic and are able to deform by up to a third without breaking. This combination of strength, flexibility, and small size means that it is physically difficult (although not impossible) to break open virus particles by physical pressure.

The outer surface of the virus is also responsible for recognition of and interaction with the host cell. Initially, this takes the form of binding of a specific virus-attachment protein to a cellular receptor molecule. However, the capsid also has a role to play in initiating infection by delivering the genome in a form in which it can interact with the host cell. In some cases, this is a simple process that consists only of dumping the genome into the cytoplasm of the cell. In other cases, this process is much more complex, for example, retroviruses carry out extensive modifications to the virus genome while it is still inside the particle, converting two molecules of single-stranded RNA to one molecule of double-stranded DNA before delivering it to the cell nucleus. Beyond protecting the genome, this function of the capsid is vital in allowing viruses to establish an infection.

In order to form particles, viruses must overcome two fundamental problems. First, they must assemble the particle using only the information available from the components that make up the particle itself. Second, virus particles form regular geometric shapes, even though the proteins from which they are made are irregular. How do these simple organisms solve these difficulties? The solutions to both problems lie in the rules of symmetry.

Capsid Symmetry and Virus Architecture

It is possible to imagine a virus particle, the outer shell of which (the capsid) consists of a single, hollow protein molecule, which folds up trapping the virus genome inside. In practice, this arrangement cannot occur, for the following reason. The triplet nature of the genetic code means that three nucleotides (or base pairs, in the case of viruses with double-stranded genomes) are necessary to encode one amino acid. As parasites, viruses cannot use an alternative, more economical, genetic code because this could not be read by the host cell. Because the approximate molecular weight of a nucleotide triplet is 1,000 g/mol and the average molecular weight of a single amino acid is 150 g/mol, a nucleic acid can only encode a protein that is at most 15% of its own weight. For this reason, virus capsids must be made up of multiple protein molecules (subunit construction), and viruses must solve the problem of how these subunits are arranged to form a stable structure.

In 1957, Fraenkel-Conrat and Williams showed that when mixtures of purified tobacco mosaic virus (TMV) RNA and coat protein are incubated together, virus particles formed. The discovery that virus particles could form spontaneously from purified subunits without any extra information indicates that the particle is in the free energy minimum state and is the most energetically favored structure of the components. This inherent stability is an important feature of virus particles. Although some viruses are very fragile and unable to survive outside the protected host cell environment, many are able to persist for long periods, in some cases for years.

The forces that drive the assembly of virus particles include hydrophobic and electrostatic interactions. Only rarely are covalent bonds involved in holding together the subunits. In biological terms, this means that protein–protein, protein–nucleic acid, and protein–lipid interactions are involved. We now have a good understanding of general principles and repeated structural motifs that appear to govern the construction of many diverse, unrelated viruses. These are discussed below under the two main classes of virus structures: helical and icosahedral symmetry.

Helical Capsids

TMV is representative of one of the two major structural classes seen in virus particles, those with helical symmetry. The simplest way to arrange multiple, identical protein subunits is to use rotational symmetry and to arrange the irregularly shaped proteins around the circumference of a circle to form a disk. Multiple disks can then be stacked on top of one another to form a cylinder, with the virus genome coated by the protein shell or contained in the hollow center of the cylinder. Denaturation studies of TMV suggest that this is the form this virus particle takes (see Chapter 1).

Closer examination of the TMV particle by X-ray crystallography reveals that the structure of the capsid actually consists of a helix rather than a pile of stacked disks. A helix can be defined mathematically by two parameters: its amplitude (diameter) and pitch (the distance covered by each complete turn of the helix) (Figure 2.2). Helices are simple structures formed by stacking repeated components with a constant association (amplitude and pitch) to one another. If this simple relationship is broken, a spiral forms rather than a helix, and a spiral is unsuitable for containing and protecting a virus genome. In terms of individual protein subunits, helices are described by the number of...