18.03.1 Introduction to viruses

Viruses are small (20-30 nm) infective agents that require a host cell (e.g. human cells) to replicate. When a virus is outside of the host, it is known as a virion. A virion is either a segment of RNA or DNA enclosed in a protein coat, which is called the capsid. The capsid containing the nucleic acid (RNA or DNA) is called the nucleocapsid. Viruses may also have an outer lipoprotein envelope. Also, viruses may contain some enzymes required for replication in the host cell. The actual structure varies between different types of viruses.

There are 3 types of viruses; DNA viruses, RNA viruses, and retroviruses. Examples of DNA viruses include herpesviruses, which can manifest itself as chickenpox, shingles, cold sores, or glandular fever. Other common examples of DNA viruses are the adenoviruses which can cause sore throat, and conjunctivitis. DNA viruses enter the host cell nucleus, and then they use the host cell RNA polymerase for transcription of their own DNA to viral RNA (Figure 18.3). This is followed by translation and viral protein synthesis.

Figure 18.3 Initial action of viruses (Copyright QUT, Sheila Doggrell) DNA v and RNAv are viral DNA and RNA respectively

The RNA viruses include the viruses responsible for influenza and German measles, as well as the paramyxoviruses (cause measles, mumps) and picornaviruses (cause colds, meningitis, poliomyelitis). The RNA of the RNA viruses is translated by the host enzyme systems to form the protein required for the synthesis of new virions (Figure 18.3).

The best known example of a retrovirus is human immunodeficiency virus (HIV). HIV underlies acquired immunodeficiency syndrome (AIDS), which gives the person an increased susceptibility to infections and cancer.

Retroviruses contain RNA as their genetic material, but in order for viral replication to occur, DNA must first be synthesised from the RNA template. This step involves a viral specific enzyme reverse transcriptase enzyme (virus RNA-dependent DNA polymerase), which makes a DNA copy of the viral RNA (Figure 18.3). Then, the DNA copy becomes part of host genome, known as provirus. The provirus DNA is transcripted and mRNA translated by the host to make new virus particles.

The chemotherapy of viral infections is dependent on the identification of viral specific proteins that can be selective targets for antiviral drugs. While such targets have been identified, these are usually specific for a particular virus and therefore broad spectrum antiviral drugs are not available. For this reason, the drugs are often classified according to the virus they act against rather than their mechanism of action. Furthermore, all of the currently used antiviral drugs are virustatic. They are only active against the actively replicating cell and interfere with the spread of the infection. As they do not kill any dormant forms of the virus, the dormant form of the virus may become active long after the initial infection (e.g. the herpes simplex virus is responsible for shingles long after an initial infection of chickenpox).

There are a number of ways (targets) antiviral drugs can inhibit the virus. These include inhibiting the attachment to and entry into the host cell of the virus, inhibition of the release of viral DNA/RNA and inhibition of the replication of viral DNA/RNA. Alternative ways antiviral drugs can inhibit the action of viruses is to inhibit the assembly of new viral particles or the release of viral particles from the infected cell