Chapter six - Viruses v2

[Pages:26]Chapter 6

Viruses: At the Threshold of Life

Objectives: After reading Chapter Six, you should understand... ? How viruses were discovered. ? The structures of viruses and how they differ from bacteria. ? Virus replication and how viruses cause disease. ? How to control viruses.

The SARS virus was near pandemic between November 2002 and July 2003, with 8,096 known infected cases and 774 deaths.

Viruses have been described at being somewhere between chemicals and living objects. Why?

The discovery and structure of viruses

As we have discussed, between 1880 and 1915 discoveries boomed in the field of microbiology.

Tuberculosis, typhoid fever, syphilis and other diseases were becoming understood.

Methods of food preservation and sanitation against bacterial contamination were improving.

Bacteria were being used in industry to benefit society.

However, research into the causes of diseases such as chickenpox, measles, polio and hepatitis was unproductive.

Why?

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Two viruses have been keys to the development of virology

1. Smallpox virus - More than 300 million people died from smallpox from 1900 to 1978.

How many have died from HIV AIDS?

Typical lesions resulting from infection with the variola virus. From: idph.state.il.us/Bioterrorism/spoxphoto1.htm

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Smallpox virus

In the 1500s, Europeans came to the "New World" from the West Indies...and unintentionally brought smallpox virus with them.

Shortly thereafter, over one million Aztec Indians died from smallpox (why?).

Later, British soldiers in North America used smallpox as a bioweapon during the French and Indian Wars.

Soldiers gave blankets that had been used by smallpox patients, as "gifts", to American Indians with the intent of infecting them with smallpox.

Smallpox epidemics wiped out more than 50% of the affected tribes.

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The cause and the first cure Smallpox is caused by the variola virus that emerged in human populations thousands of years ago.

Highly contagious and spreads from person to person primarily by: (i) droplets or aerosols expelled from the throat of infected persons, and (ii) direct contact.

The infectious dose is unknown, but is believed to be only a few virons. 1796 - Edward Jenner showed that people who were in frequent contact with

cows did not get smallpox. He realized that an infection caused by cowpox, a relative of smallpox, provided protection against smallpox. Pus from cowpox blisters became the first smallpox vaccination...why did this work?

Cowpox vaccine was first isolated by Jenner from a cow named Blossom, whose hide hangs on the wall of the library at St George's medical school in England.

In the 1960's and 1970's in Europe, during a very limited smallpox outbreak, individuals with the infection transmitted smallpox to as many as 10 to 20 other people, called second-generation infections.

These are the worrisome infections. Why?

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Except for laboratory stockpiles, smallpox virus has been eliminated due to a massive worldwide eradication program throughout the 20th century. The last case of smallpox in the United States was in 1949. The last naturally occurring case in the world was in Somalia in 1977.

Variola minor in 23-year-old Ali Maow Maalin, Merka, Somalia. Photograph from World Health Organization.

To this day, smallpox is the only human infectious disease to have been completely eradicated.

In the aftermath of the terrorist events of September, 2001, there is heightened concern that the variola virus might be used as an agent of bioterrorism.

If smallpox was eradicated over 30 years ago due to effective vaccination, then why is the potential devastation of smallpox re-introduction so great?

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2. Tobacco mosaic virus (TMV)

Dmitri Iwanowski (1892) researched tobacco mosaic virus, which causes tobacco leaves to shrivel and die.

Normal tobacco leaves

Tobacco leaves infected with TMV

Iwanowski attempted to determine the nature of the infectious agent. He crushed diseased leaves and filtered the "mush" to separate the solids from liquids.

The filter was designed to trap bacteria, so presumably, the liquid portion was not infective.

BUT

The liquid portion was still infectious. What could be happening?

Martinus Beijerinck (1898) repeated Iwanowski's work and found that even when very dilute, the fluid was still infective.

Clearly the agent that caused TMV persisted despite filtration and was infectious at very low concentrations.

1930s ? viruses were finally crystallized.

Once the electron microscope was invented in the 1940s, the tobacco mosic virus was visualized.

How does this timeline compare with that of bacteriology?

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The structure of viruses

Many people can name some popular viruses (influenza, HIV) but cannot tell you much about them.

Virus sizes and configurations vary

Viruses are quite different from typical animal, plant, or bacteria cells.

Viruses contain a core of nucleic acid (genome) enclosed in a coat of protein (capsid).

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The viral genome is made up of either DNA or RNA, but not both,

BUT

It is not a genome as we think of one, because it is not a complete set of genes...which is why viruses need the help of a host to function.

The genes contained in the viral genome are limited to those used to build more viruses (structural genes).

The outer coat is called a capsid ? made up of protein subunits called capsomeres.

The capsid protects the virus from:

1. Physical damage - Shearing by mechanical forces.

2. Chemical damage- UV irradiation (from sunlight).

3. Enzymatic damage - Nucleases derived from dead or leaky cells or deliberately secreted by vertebrates as defense against infection.

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A viral envelope (lipids, proteins and carbohydrates) is sometimes present and is similar to a cell membrane.

1. Contains proteins called recognition factors that identify it as a viral structure and determine what type of cells the virus will infect. Why might this be important to the host cell?

2. Protects the virus 3. Aids with host cell penetration.

In order for a virus to infect a host cell, it must be able to attach. Attachment is achieved in some viruses with the help of spikes on the envelope HIV, influenza are examples of viruses that have spikes.

HIV structure including RNA (yellow), capsid (red), envelope (blue) and spikes (brown).

Smallpox and TMV do not have spikes

Because spikes are so important for infectivity, they are often a target of antiviral chemotherapy.

The mode of action of the flu drugs Relenza, Zanamivir and Tamiflu is based on inactivating the viral protein neuraminidase, which is a component of the spikes.

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