Introduction to viruses

A virus is a tiny

Viruses are made of either two or three parts. All include genes. These genes contain the encoded biological information of the virus and are built from either DNA or RNA. All viruses are also covered with a protein coat to protect the genes. Some viruses may also have an envelope of fat-like substance that covers the protein coat, and makes them vulnerable to soap. A virus with this "viral envelope" uses it—along with specific receptors—to enter a new host cell. Viruses vary in shape from the simple helical and icosahedral to more complex structures. Viruses range in size from 20 to 300 nanometres; it would take 33,000 to 500,000 of them, side by side, to stretch to 1 centimetre (0.4 in).

Viruses spread in many ways. Although many are very specific about which host species or

can treat life-threatening infections. Those vaccines that produce lifelong immunity can prevent some infections.

Virus glossary
Virion A single, virus particle outside its host cell, it can be defective and non-infectious
Capsid The protein shell surrounding the virus's genes; this shell is made from many smaller proteins which are identical and are called capsomers.
Envelope Some viruses have a bubble of fat that surrounds the virion.
Gene A segment of DNA or RNA; genes are like sentences made of the "letters" of the nucleotide alphabet. Genes direct the reproduction of viruses. Different types of viruses have genes made from DNA or RNA but not both.
Host range The animals, plants or bacteria that any one type of virus can infect.
Bacteriophages The viruses that reproduce in bacteria.
Cell tropism The type of cell in which a virus can reproduce.
Serotype A grouping of viruses based on the antigens on the surface of virus.
Symmetry All viruses of a type are identical and their particles have a cubical, helical or complex structure.
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Discovery

In 1884, French microbiologist Charles Chamberland invented the Chamberland filter (or Chamberland–Pasteur filter), that contains pores smaller than bacteria. He could then pass a solution containing bacteria through the filter, and completely remove them. In the early 1890s, Russian biologist Dmitri Ivanovsky used this method to study what became known as the tobacco mosaic virus. His experiments showed that extracts from the crushed leaves of infected tobacco plants remain infectious after filtration.^[2]

At the same time, several other scientists showed that, although these agents (later called viruses) were different from bacteria and about one hundred times smaller, they could still cause disease. In 1899, Dutch microbiologist

Viruses co-exist with life wherever it occurs. They have probably existed since living cells first evolved. Their origin remains unclear because they do not fossilize, so molecular techniques have been the best way to hypothesise about how they arose. These techniques rely on the availability of ancient viral DNA or RNA, but most viruses that have been preserved and stored in laboratories are less than 90 years old.^[13][14] Molecular methods have only been successful in tracing the ancestry of viruses that evolved in the 20th century.^[15] New groups of viruses might have repeatedly emerged at all stages of the evolution of life.^[16] There are three major theories about the origins of viruses:^[16][17]

Regressive theory

Viruses may have once been small cells that

Chlamydia are living cells that, like viruses, can reproduce only inside host cells. This lends credence to this theory, as their dependence on being parasites may have led to the loss of the genes that once allowed them to live on their own.^[18]

Cellular origin theory

Some viruses may have evolved from bits of DNA or RNA that "escaped" from the genes of a larger organism. The escaped DNA could have come from plasmids—pieces of DNA that can move between cells—while others may have evolved from bacteria.^[19]

Coevolution theory

Viruses may have evolved from complex molecules of protein and DNA at the same time as cells first appeared on earth, and would have depended on cellular life for many millions of years.^[20]

There are problems with all of these theories. The regressive hypothesis does not explain why even the smallest of cellular parasites do not resemble viruses in any way. The escape or the cellular origin hypothesis does not explain the presence of unique structures in viruses that do not appear in cells. The coevolution, or "virus-first" hypothesis, conflicts with the definition of viruses, because viruses depend on host cells.^[20][21] Also, viruses are recognised as ancient, and to have origins that pre-date the divergence of life into the three domains.^[22] This discovery has led modern virologists to reconsider and re-evaluate these three classical hypotheses.^[16][22]

Structure

A virus particle, also called a

Viruses are among the smallest infectious agents, and are too small to be seen by

The genes of viruses are made from DNA (deoxyribonucleic acid) and, in many viruses, RNA (ribonucleic acid). The biological information contained in an organism is encoded in its DNA or RNA. Most organisms use DNA, but many viruses have RNA as their genetic material. The DNA or RNA of viruses consists of either a single strand or a double helix.^[28]

Viruses can reproduce rapidly because they have relatively few genes. For example, influenza virus has only eight genes and rotavirus has eleven. In comparison, humans have 20,000–25,000. Some viral genes contain the code to make the structural proteins that form the virus particle. Other genes make non-structural proteins found only in the cells the virus infects.^[29][30]

All cells, and many viruses, produce proteins that are enzymes that drive chemical reactions. Some of these enzymes, called DNA polymerase and RNA polymerase, make new copies of DNA and RNA. A virus's polymerase enzymes are often much more efficient at making DNA and RNA than the equivalent enzymes of the host cells,^[31] but viral RNA polymerase enzymes are error-prone, causing RNA viruses to mutate and form new strains.^[32]

In some species of RNA virus, the genes are not on a continuous molecule of RNA, but are separated. The influenza virus, for example, has eight separate genes made of RNA. When two different strains of influenza virus infect the same cell, these genes can mix and produce new strains of the virus in a process called reassortment.^[33]

Protein synthesis

Transcription is the process where information in DNA, called the genetic code, is used to produce RNA copies called messenger RNA (mRNA). These migrate through the cell and carry the code to ribosomes where it is used to make proteins. This is called translation because the protein's amino acid structure is determined by the mRNA's code. Information is hence translated from the language of nucleic acids to the language of amino acids.^[34]

Some nucleic acids of RNA viruses function directly as mRNA without further modification. For this reason, these viruses are called positive-sense RNA viruses.^[35] In other RNA viruses, the RNA is a complementary copy of mRNA and these viruses rely on the cell's or their own enzyme to make mRNA. These are called negative-sense RNA viruses. In viruses made from DNA, the method of mRNA production is similar to that of the cell. The species of viruses called retroviruses behave completely differently: they have RNA, but inside the host cell a DNA copy of their RNA is made with the help of the enzyme reverse transcriptase. This DNA is then incorporated into the host's own DNA, and copied into mRNA by the cell's normal pathways.^[36]

Life-cycle

When a virus infects a cell, the virus forces it to make thousands more viruses. It does this by making the cell copy the virus's DNA or RNA, making viral proteins, which all assemble to form new virus particles.^[37]

There are six basic, overlapping stages in the life cycle of viruses in living cells:^[38]

• Attachment is the binding of the virus to specific molecules on the surface of the cell. This specificity restricts the virus to a very limited type of cell. For example, the human immunodeficiency virus (HIV) infects only human
  gp120, can only react with CD4
  and other molecules on the T cell's surface. Plant viruses can only attach to plant cells and cannot infect animals. This mechanism has evolved to favour those viruses that only infect cells in which they are capable of reproducing.
• Penetration follows attachment; viruses penetrate the host cell by endocytosis or by fusion with the cell.
• Uncoating happens inside the cell when the viral capsid is removed and destroyed by viral enzymes or host enzymes, thereby exposing the viral nucleic acid.
• Replication of virus particles is the stage where a cell uses viral messenger RNA in its protein synthesis systems to produce viral proteins. The RNA or DNA synthesis abilities of the cell produce the virus's DNA or RNA.
• Assembly takes place in the cell when the newly created viral proteins and nucleic acid combine to form hundreds of new virus particles.
• Release occurs when the new viruses escape or are released from the cell. Most viruses achieve this by making the cells burst, a process called lysis. Other viruses such as HIV are released more gently by a process called budding.

Effects on the host cell

Viruses have an extensive range of structural and biochemical effects on the host cell.^[39]These are called cytopathic effects.^[40] Most virus infections eventually result in the death of the host cell. The causes of death include cell lysis (bursting), alterations to the cell's surface membrane and apoptosis (cell "suicide").^[41] Often cell death is caused by cessation of its normal activity due to proteins produced by the virus, not all of which are components of the virus particle.^[42]

Some viruses cause no apparent changes to the infected cell. Cells in which the virus is

Common human diseases caused by viruses include the

Although viral pandemics are rare events, HIV—which evolved from viruses found in monkeys and chimpanzees—has been pandemic since at least the 1980s.^[62] During the 20th century there were four pandemics caused by influenza virus and those that occurred in 1918, 1957 and 1968 were severe.^[63] Before its eradication, smallpox was a cause of pandemics for more than 3,000 years.^[64] Throughout history, human migration has aided the spread of pandemic infections; first by sea and in modern times also by air.^[65]

With the exception of smallpox, most pandemics are caused by newly evolved viruses. These "emergent" viruses are usually mutants of less harmful viruses that have circulated previously either in humans or in other animals.^[66]

There are many types of

Bacteriophages are viruses that infect bacteria and

Animals, including humans, have many natural defences against viruses. Some are non-specific and protect against many viruses regardless of the type. This innate immunity is not improved by repeated exposure to viruses and does not retain a "memory" of the infection. The skin of animals, particularly its surface, which is made from dead cells, prevents many types of viruses from infecting the host. The acidity of the contents of the stomach destroys many viruses that have been swallowed. When a virus overcomes these barriers and enters the host, other innate defences prevent the spread of infection in the body. A special hormone called interferon is produced by the body when viruses are present, and this stops the viruses from reproducing by killing the infected cells and their close neighbours. Inside cells, there are enzymes that destroy the RNA of viruses. This is called RNA interference. Some blood cells engulf and destroy other virus-infected cells.^[78]

Adaptive immunity of animals

Specific immunity to viruses develops over time and white blood cells called lymphocytes play a central role. Lymphocytes retain a "memory" of virus infections and produce many special molecules called antibodies. These antibodies attach to viruses and stop the virus from infecting cells. Antibodies are highly selective and attack only one type of virus. The body makes many different antibodies, especially during the initial infection. After the infection subsides, some antibodies remain and continue to be produced, usually giving the host lifelong immunity to the virus.^[79]

Plant resistance

Plants have elaborate and effective defence mechanisms against viruses. One of the most effective is the presence of so-called resistance (R) genes. Each R gene confers resistance to a particular virus by triggering localised areas of cell death around the infected cell, which can often be seen with the unaided eye as large spots. This stops the infection from spreading.^[80] RNA interference is also an effective defence in plants.^[81] When they are infected, plants often produce natural disinfectants that destroy viruses, such as salicylic acid, nitric oxide and reactive oxygen molecules.^[82]

Resistance to bacteriophages

The major way bacteria defend themselves from bacteriophages is by producing enzymes which destroy foreign DNA. These enzymes, called

Vaccines simulate a natural infection and its associated immune response, but do not cause the disease. Their use has resulted in the eradication of smallpox and a dramatic decline in illness and death caused by infections such as polio, measles, mumps and rubella.^[84] Vaccines are available to prevent over fourteen viral infections of humans^[85] and more are used to prevent viral infections of animals.^[86] Vaccines may consist of either live or killed viruses.^[87] Live vaccines contain weakened forms of the virus, but these vaccines can be dangerous when given to people with weak immunity. In these people, the weakened virus can cause the original disease.^[88] Biotechnology and genetic engineering techniques are used to produce "designer" vaccines that only have the capsid proteins of the virus. Hepatitis B vaccine is an example of this type of vaccine.^[89] These vaccines are safer because they can never cause the disease.^[87]

Antiviral drugs

Since the mid-1980s, the development of antiviral drugs has increased rapidly, mainly driven by the AIDS pandemic. Antiviral drugs are often nucleoside analogues, which masquerade as DNA building blocks (nucleosides). When the replication of virus DNA begins, some of the fake building blocks are used. This prevents DNA replication because the drugs lack the essential features that allow the formation of a DNA chain. When DNA production stops the virus can no longer reproduce.^[90] Examples of nucleoside analogues are aciclovir for herpes virus infections and lamivudine for HIV and hepatitis B virus infections. Aciclovir is one of the oldest and most frequently prescribed antiviral drugs.^[91]

Other antiviral drugs target different stages of the viral life cycle. HIV is dependent on an enzyme called the

HIV infections are usually treated with a combination of antiviral drugs, each targeting a different stage in the virus's life cycle. There are drugs that prevent the virus from attaching to cells, others that are nucleoside analogues and some poison the virus's enzymes that it needs to reproduce. The success of these drugs is proof of the importance of knowing how viruses reproduce.[92]

Role in ecology

Viruses are the most abundant biological entity in aquatic environments;^[95] one teaspoon of seawater contains about ten million viruses,^[96] and they are essential to the regulation of saltwater and freshwater ecosystems.^[97] Most are bacteriophages,^[98] which are harmless to plants and animals. They infect and destroy the bacteria in aquatic microbial communities and this is the most important mechanism of recycling carbon in the marine environment. The organic molecules released from the bacterial cells by the viruses stimulate fresh bacterial and algal growth.^[99]

Microorganisms constitute more than 90% of the biomass in the sea. It is estimated that viruses kill approximately 20% of this biomass each day and that there are fifteen times as many viruses in the oceans as there are bacteria and archaea. They are mainly responsible for the rapid destruction of harmful algal blooms,^[100] which often kill other marine life.^[101] The number of viruses in the oceans decreases further offshore and deeper into the water, where there are fewer host organisms.^[102]

Their effects are far-reaching; by increasing the amount of respiration in the oceans, viruses are indirectly responsible for reducing the amount of carbon dioxide in the atmosphere by approximately 3

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References

Notes