3 The viruses
Viruses share some common structural features
• The genetic material, in the form of single-stranded (ss) or double-stranded (ds), linear or circular RNA or DNA, is contained within a coat or capsid, made up of a number of individual protein molecules (capsomeres).
• The complete unit of nucleic acid and capsid is called the ‘nucleocapsid’, and often has a distinctive symmetry depending upon the ways in which the individual capsomeres are assembled (Fig. 3.1). Symmetry can be icosahedral, helical or complex.
• In many cases, the entire virus particle or ‘virion’ consists only of a nucleocapsid. In others, the virion consists of the nucleocapsid surrounded by an outer envelope or membrane (Fig. 3.2). This is generally a lipid bilayer of host cell origin, into which virus proteins and glycoproteins are inserted.
Infection of host cells
The stages involved in infection of host cells are summarized in Figure 3.3 (see also Fig. 2.6).
Virus particles enter the body of the host in many ways
The most common forms of virus transmission (Fig. 3.4; see Ch. 13) are:
• via inhaled droplets (e.g. rhinovirus, influenza viruses)
• in food or water (e.g. hepatitis A virus, noroviruses)
• by direct transfer from other infected hosts (e.g. HIV, hepatitis B virus)
• from bites of vector arthropods (e.g. yellow fever virus, West Nile virus).
Viruses show host specificity and usually infect only one or a restricted range of host species. The initial basis of specificity is the ability of the virus particle to attach to the host cell
The process of attachment to, or adsorption by, a host cell depends on general intermolecular forces, then on more specific interactions between the molecules of the nucleocapsid (in naked viruses) or the virus membrane (in enveloped viruses) and the molecules of the host cell membrane. In many cases, there is a specific interaction with a particular host molecule, which therefore acts as a receptor. Influenza virus, for example, attaches by its haemagglutinin to a glycoprotein (sialic acid) found on cells of mucous membranes and on red blood cells; other examples are given in Table 3.1. Attachment to the receptor is followed by entry into the host cell.
Table 3.1 Viruses may use more than one receptor to gain entry into the host cell
| Cell membrane receptors for virus attachment | |
|---|---|
| Virus | Receptor molecule |
| Influenza | Sialic acid receptor on lung epithelial cells and upper respiratory tract |
| Rabies | Acetylcholine receptor Neuronal cell adhesion molecule |
| HIV | CD4: Primary receptor CCR5 or CXCR4: chemokine receptors |
| Epstein–Barr virus | C3d receptor on B cells |
| Human parvovirus B19 | P antigen on erythoid progenitor cells Ku80 antoantigen coreceptor |
| Hepatitis C virus | Epidermal growth factor receptor and ephrin receptor A2 are host co-factors for viral entry |
| Human rhinoviruses | Divided into two groups based on receptor binding: Major group: intercellular adhesion molecule 1 (ICAM-1) Minor group: very low density lipoprotein receptor (VLDL-R) |
Replication
RNA viruses produce mRNA by several different routes
In dsRNA viruses, one strand is first transcribed by viral polymerase into mRNA (Fig. 3.5). In ssRNA viruses, there are three distinct routes to the formation of mRNA:
1. Where the single strand has the positive (+) sense configuration (i.e. has the same base sequence as that required for translation), it can be used directly as mRNA.
2. Where the strand has the negative (–) sense configuration, it must first be transcribed, using viral polymerase, into a positive sense strand, which can then act as mRNA.
3. Retroviruses follow a completely different route. Their positive sense ssRNA is first made into a negative sense ssDNA, using the viral reverse transcriptase enzyme carried in the nucleocapsid, and dsDNA is then formed which enters the nucleus and becomes integrated into the host genome. This integrated viral DNA is then transcribed by host polymerase into mRNA.
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