Lecture 2 Viruses

Definition
A virus is an infectious agent that has a genome (genetic material) containing
either DNA or RNA, and can alternate between two distinct states,
intracellular and extracellular.

History
Robert Koch had put forward the germ theory of disease. People were
confident that for each disease there would be a micro-organism that would
be:
a) seen with a microscope;
b) grown on a nutrient medium;
c) stopped by filters.

However Iwanowski in 1892 showed that the causal agent of the disease
Tobacco Mosaic passed through a filter and it couldn’t be seen or grown.

Following this Loeffler and Frosch came to the same conclusions in 1898
regarding the causal agent of foot and mouth disease.

Ellerman and Bang in1908 reported the cell-free transmission of chicken

leukaemia. This was the first indication that some viruses can cause cancer.

In 1917 d’Herelle noted that cultures of the bacterium that causes dysentery
were lysed by filtered emulsions of faeces. d’Herelle was dealing with a
bacterial virus or bacteriophage (phage for short).

Viruses have been shown to infect all types of cells: bacteria, fungi, insect
cells, plant cells, mammalian cells etc.

General Structure
Viruses are submicroscopic (too small to be seen with a light microscope).
They consist of nucleic acid surounded by a protein coat., and occasionally
other components (eg membranes derived from host cells). These particles
(virions) are metabolically inert on their own.

Function
Their role is to carry nucleic acid from one cell to another, so that a new cell
can become infected. The host cell performs the metabolic functions
necessary for virus replication. As part of this the result can be lysis of the cell
- the lytic cycle. Eg the virus T4 causes the lysis of Escherichia coli. Note it
is the host cell metabolism that is taken over to produce the new virions.
Without the host cell new particles cannot be made. After release the virus
particle may, or may not, come across an un-infected cell.

Alternatively the genetic material of the virus can integrate with the host cell
(eg the phage lambda infecting E. coli). As the genetic material is replicated,
so is the DNA of the virus (the lysogenic cycle). Occasionally an induction
event makes the cells lyse and the lytic cycle starts.
Detailed structure
Three examples

a) based on the icosahedron. This consists of 20 triangular faces. Example is

the adenovirus. This is 70 nm across and contains DNA as the nucleic acid.
b) rod shaped viruses. eg the Tobacco Mosaic virus has an RNA core
surrounded by a protein coat.
c) tailed viruses. eg bacteriophage T4 which attacks and lyses E. coli.

Some viruses have a membranous outer layer which derives from the host
cell as the virus is released - the envelope. eg Influenza virus, HIV.

Naming of viruses
Not very systematic!
Viral names are not italicised or underlined. They are often named after the
disease that is caused: eg Turnip crinkle virus, Tobacco mosaic virus,
Influenza virus.

Viral diseases
Examples include: Flu, Colds, Smalpox, Rabies, Chicken Pox, German
Measles, Measles, Polio, Hepatitis, certain tumours, AIDS, caused by Human
Immunodeficiency Virus HIV.

Many of these diseases are now rare in this country. A good example is
Smallpox, which has been eradicated from the world. The last natural case
was in Ethiopia in 1977, although a worker in a Birmingham Hospital died
from it in 1978.
Two hundred years ago there was great mortality from smallpox; it killed 25%
of all children born. In 1950 in India 41,000 people died from the disease.
This has been overcome by vaccination programmes. This was developed
by Edward Jenner who used the cowpox virus (Vaccinia) to immunize
against smallpox.

Detection
Viruses can be detected by observing their effect on host cells grown in
culture. ie do they cause a cytopathic effect (kill the cells)?

Treatment
Viruses depend on the host cells for many of the functions of viral replication.
It is therefore difficult to inhibit virus replication wihout affecting the host cell.
There are many more antibacterial compounds (because there are many
more sites to attack eg cell walls) than there are antiviral compounds.
eg
a) Acyclovir which inhibits DNA synthesis in the herpes virus (cold sores)
b) Idoxuridine which is used for herpes eye infections. again inhibits DNA
synthesis. Cells of the cornea are not actively dividing, so no effect on the
host.
c) Azidothymidine (AZT) is a thymidine analogue which inhibits the action of
the enzyme reverse transcriptase in the retrovirus HIV. This converts RNA to
DNA, a necessary step in replication of the virus which is not carried out in
human cells.