Viruses: Structure and Replication Cycles

1Overview

A virus can sit on a doorknob for hours with no sign of life, then enter a cell and turn it into a factory that produces thousands of copies of the virus. Is such a thing alive? Biologists still argue about it, and that argument is useful because it forces a closer look at what life means. This lesson covers virus structure, the reasons viruses sit at the boundary of living and non-living, and the two ways a virus can take over a host cell: the lytic and lysogenic cycles. The next lesson uses this knowledge to explain viral disease and how it is controlled.

2What a virus is made of

A single virus particle is called a virion. Its structure is far simpler than that of any cell. Most virions have three parts:

• A nucleic acid genome in the core. It can be DNA or RNA, single-stranded or double-stranded, linear or circular. Some genomes are segmented: the influenza genome is split into separate pieces.
• A protein coat called a capsid, built from many repeating protein units (capsomeres), that protects the genome.
• An envelope (in some viruses): an outer layer of membrane taken from the host cell, studded with viral proteins.

Capsids come in several shapes: helical (a spiral tube), icosahedral (a many-sided polyhedron) and complex forms such as the head-and-tail design of some bacteriophages (viruses that infect bacteria). Enveloped viruses are generally more fragile than non-enveloped viruses, which resist heat, pH changes and some disinfectants better.

Most virions are about 20 to 250 nanometres across, so they are too small to see with a light microscope. They were first visualized with the electron microscope in the late 1930s. A few giant viruses from amoebae reach about 1000 nm, still much smaller than most cells.

3At the boundary of living and non-living

Whether viruses are alive depends on the definition of life used. Biology textbooks list properties shared by living things: order and cellular organization, response to stimuli, reproduction, growth and development, regulation, energy processing and evolution. Compare viruses against that list:

Viruses therefore have some features of life (genes, replication through a host, evolution) and lack others (cells, independent metabolism). Because of this they are often described as at the boundary of living and non-living. Outside a host, a virion is inert, a package of molecules. Inside a host, it directs the cell's machinery to produce more virions.

Where did viruses come from?

Viruses do not fossilize, so their origins remain largely unknown, and most scholars agree they do not share a single common ancestor. Three hypotheses are discussed:

• Regressive hypothesis: viruses evolved from free-living cells or intracellular parasites that lost most of their genes.
• Progressive (escapist) hypothesis: viruses arose from genetic molecules or mobile elements that escaped from host cells.
• Virus-first hypothesis: viruses may have been self-replicating entities before the first cells appeared.

Host specificity

A virus can infect only cells that carry the right surface molecule to act as a receptor. The match between viral protein and host receptor works like a lock and key. For example, HIV attaches to the CD4 molecule on certain white blood cells. Viruses infect nearly all forms of life, including bacteria, archaea, plants, animals and fungi, but each virus has a limited host range. Interestingly, host complexity does not predict virus complexity: some of the most complex virions infect bacteria.

4The viral replication cycle

Whatever the virus, the infection of a host cell follows a general pattern:

1. Attachment. The virus binds a specific receptor on the host cell.
2. Entry. Bacteriophages inject their nucleic acid and leave the capsid outside. Animal viruses enter by endocytosis or by fusing their envelope with the cell membrane, and the capsid then breaks down to release the genome.
3. Replication and assembly. The viral genome is copied and viral proteins are made, using host enzymes and ribosomes. New virions are assembled.
4. Release. Progeny virions leave the cell, either by killing it or by budding out without immediately killing it.

The lytic cycle

In the lytic cycle, the virus completes all four steps quickly. The phage takes over the host, makes many new virions and bursts (lyses) the cell to release them. The cell dies. A virus that follows only this route is called a virulent virus. The T4 phage is an example of a lytic phage.

The lysogenic cycle

In the lysogenic cycle, the virus does not make new virions at once. Instead, its DNA joins the host genome, where it is called a prophage, and is copied every time the host divides. The host bacterium continues to live and reproduce, and every daughter cell carries the viral DNA. Lambda phage is a classic lysogenic example. Stresses such as starvation or toxic chemicals can trigger the prophage to leave the chromosome and switch to the lytic cycle.

5Animal viruses and retroviruses

Animal viruses use the same four steps but with differences. Non-enveloped viruses enter by endocytosis or by forming channels in the membrane. Enveloped viruses enter by endocytosis or by fusion of the envelope with the cell membrane, and their progeny often leave by budding, taking a piece of host membrane as a new envelope. Non-enveloped progeny are usually released when the cell lyses or undergoes apoptosis.

Some animal viruses can persist in a latent state. Herpesviruses, for example, can remain in nervous tissue making little or no viral protein, then reactivate and cause lesions later, as in cold sores and shingles. This is the animal-cell counterpart of lysogeny: a quiet period followed by reactivation.

HIV: a retrovirus

A retrovirus such as HIV has an RNA genome. After entering a host cell, the enzyme reverse transcriptase copies the RNA into DNA, and this DNA is integrated into the host genome. It then behaves like a prophage: it is copied with the cell's own DNA and can be used to make new virions. Because reverse transcriptase is a viral enzyme and not a host enzyme, antiviral drugs can target it without greatly disturbing normal cell metabolism.

6Viruses compared with bacteria

Viruses and bacteria are often grouped together as "germs", but they are very different, and the difference matters for treatment.

Because a virus uses the host cell's own machinery, a drug that damaged the virus's replication too broadly would also damage the host. Effective antiviral drugs therefore usually target something specific to the virus, such as a viral enzyme. Antibiotics target bacteria and have no effect on viruses, which is why they do not help with colds (see the article on antibiotics and colds).

7Classifying viruses

Viruses were first grouped by shape, then by the type of nucleic acid and whether it is single- or double-stranded. The system most widely used today, the Baltimore classification, groups viruses by how they produce messenger RNA. There are seven groups: double-stranded DNA; single-stranded DNA; double-stranded RNA; positive-sense single-stranded RNA; negative-sense single-stranded RNA; single-stranded RNA with reverse transcriptase (retroviruses such as HIV); and double-stranded DNA with reverse transcriptase (such as hepatitis B). This course does not require memorizing the groups, but the existence of the system shows that viruses cannot be placed on the tree of life in the same way as cells. That point is revisited in the classification lesson.

8Summary

• A virion is a nucleic acid genome in a protein capsid, sometimes with an envelope, usually 20 to 250 nm across.
• Viruses have genes and evolve but lack cells and independent metabolism, so they sit at the boundary of living and non-living.
• Host specificity depends on a match between viral proteins and host receptors.
• Replication has four steps: attachment, entry, replication and assembly, and release.
• In the lytic cycle the host is destroyed; in the lysogenic cycle viral DNA joins the host genome as a prophage and is copied until a trigger switches it to the lytic cycle.
• Retroviruses such as HIV copy RNA into DNA with reverse transcriptase and integrate it into the host genome.

?Quick check

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