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Virus.

 

virus (from the Latin virus meaning toxin or poison) is a small infectious agent that can replicate only inside the living cells of other organisms. Most viruses are too small to be seen directly with a light microscope. Viruses infect all types of organisms, from animals and plants to bacteria and archaea.<  Since the initial discovery of tobacco mosaic virus by Martinus Beijerinck in 1898,  about 5,000 viruses have been described in detail,  although there are millions of different types. Viruses are found in almost every ecosystem on Earth and these minute structures are the most abundant type of biological entity. The study of viruses is known as virology, a sub-specialty of microbiology.

Unlike prions and viroids, viruses consist of two or three parts: all viruses have genes made from either DNA or RNA, long molecules that carry genetic information; all have a protein coat that protects these genes; and some have an envelope of lipids that surrounds them when they are outside a cell. (Viroids do not have a protein coat and prions contain no RNA or DNA.) Viruses vary from simple helical and icosahedral shapes to more complex structures. Most viruses are about one hundred times smaller than an average bacterium. The origins of viruses in the evolutionary history of life are unclear: some may have evolved from plasmids—pieces of DNA that can move between cells—while others may have evolved from bacteria. In evolution, viruses are an important means of horizontal gene transfer, which increases genetic diversity.

Viruses spread in many ways; plant viruses are often transmitted from plant to plant by insects that feed on sap, such as aphids, while animal viruses can be carried by blood-sucking insects. These disease-bearing organisms are known as vectors. Influenza viruses are spread by coughing and sneezing. The norovirus and rotavirus, common causes of viral gastroenteritis, are transmitted by the faecal-oral route and are passed from person to person by contact, entering the body in food or water. HIV is one of several viruses transmitted through sexual contact and by exposure to infected blood. Viruses can infect only a limited range of host cells called the "host range". This can be broad as when a virus is capable of infecting many species or narrow.

Viral infections in animals provoke an immune response that usually eliminates the infecting virus. Immune responses can also be produced by vaccines, which confer an artificially acquired immunity to the specific viral infection. However, some viruses including those causing HIV and viral hepatitis evade these immune responses and result in chronic infections. Microorganisms also have defenses against viral infection, such as restriction modification systems which restrict the growth of viruses. Antibiotics have no effect on viruses, but several antiviral drugs have been developed.

 

Origins

Viruses are found wherever there is life and have probably existed since living cells first evolved.  The origin of viruses is unclear because they do not form fossils, so molecular techniques have been the most useful means of investigating how they arose.  These techniques rely on the availability of ancient viral DNA or RNA, but, unfortunately, most of the viruses that have been preserved and stored in laboratories are less than 90 years old. There are three main hypotheses that try to explain the origins of viruses:

Regressive hypothesis 
Viruses may have once been small cells that parasitized larger cells. Over time, genes not required by their parasitism were lost. The bacteria rickettsia and chlamydia are living cells that, like viruses, can reproduce only inside host cells. They lend support to this hypothesis, as their dependence on parasitism is likely to have caused the loss of genes that enabled them to survive outside a cell. This is also called the degeneracy hypothesis.
Cellular origin hypothesis 
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 naked DNA that can move between cells) or transposons (molecules of DNA that replicate and move around to different positions within the genes of the cell). Once called "jumping genes", transposons are examples of mobile genetic elements and could be the origin of some viruses. They were discovered in maize by Barbara McClintock in 1950.This is sometimes called the vagrancy hypothesis.
Coevolution hypothesis 
Viruses may have evolved from complex molecules of protein and nucleic acid at the same time as cells first appeared on earth and would have been dependent on cellular life for many millions of years. Viroids are molecules of RNA that are not classified as viruses because they lack a protein coat. However, they have characteristics that are common to several viruses and are often called subviral agents.  Viroids are important pathogens of plants. They do not code for proteins but interact with the host cell and use the host machinery for their replication. The hepatitis delta virus of humans has an RNA genome similar to viroids but has protein coat derived from hepatitis B virus and cannot produce one of its own. It is therefore a defective virus and cannot replicate without the help of hepatitis B virus. Similarly, the virophage 'sputnik' is dependent on mimivirus, which infects the protozoan Acanthamoeba castellanii.  These viruses that are dependent on the presence of other virus species in the host cell are called satellites and may represent evolutionary intermediates of viroids and viruses.

Prions are infectious protein molecules that do not contain DNA or RNA. They cause an infection in sheep called scrapie and cattle bovine spongiform encephalopathy ("mad cow" disease). In humans they cause kuru and Creutzfeldt-Jakob disease. They are able to replicate because some proteins can exist in two different shapes and the prion changes the normal shape of a host protein into the prion shape. This starts a chain reaction where each prion protein converts many host proteins into more prions, and these new prions then go on to convert even more protein into prions. Although they are fundamentally different from viruses and viroids, their discovery gives credence to the idea that viruses could have evolved from self-replicating molecules  Computer analysis of viral and host DNA sequences is giving a better understanding of the evolutionary relationships between different viruses and may help identify the ancestors of modern viruses. To date, such analyses have not helped to decide on which of these hypotheses are correct. However, it seems unlikely that all currently known viruses have a common ancestor and viruses have probably arisen numerous times in the past by one or more mechanisms.

Are viruses alive ?

Opinions differ on whether viruses are a form of life, or organic structures that interact with living organisms. They have been described as "organisms at the edge of life", since they resemble organisms in that they possess genes and evolve by natural selection, and reproduce by creating multiple copies of themselves through self-assembly. Although they have genes, they do not have a cellular structure, which is often seen as the basic unit of life. Viruses do not have their own metabolism, and require a host cell to make new products. They therefore cannot naturally reproduce outside a host cell although bacterial species such as rickettsia and chlamydia are considered living organisms despite the same limitation. Accepted forms of life use cell division to reproduce, whereas viruses spontaneously assemble within cells. They differ from autonomous growth of crystals as they inherit genetic mutations while being subject to natural selection. Virus self-assembly within host cells has implications for the study of the origin of life, as it lends further credence to the hypothesis that life could have started as self-assembling organic molecules.

 

Replication cycle

Viral populations do not grow through cell division, because they are acellular; instead, they use the machinery and metabolism of a host cell to produce multiple copies of themselves, and they assemble in the cell.

A typical virus replication cycle
 
Some Bacteriophages inject their genomes into bacterial cells

The life cycle of viruses differs greatly between species but there are six basic stages in the life cycle of viruses:

bulletAttachment is a specific binding between viral capsid proteins and specific receptors on the host cellular surface. This specificity determines the host range of a virus. For example, HIV infects only human T cells, because its surface protein, gp120, can interact with CD4 and receptors on the T cell's surface. This mechanism has evolved to favor those viruses that only infect cells in which they are capable of replication. Attachment to the receptor can induce the viral-envelope protein to undergo changes that results in the fusion of viral and cellular membranes.
bulletPenetration follows attachment; viruses enter the host cell through receptor mediated endocytosis or membrane fusion. This is often called viral entry. The infection of plant cells is different from that of animal cells. Plants have a rigid cell wall made of cellulose and viruses can only get inside the cells after trauma to the cell wall. Viruses such as tobacco mosaic virus can also move directly in plants, from cell to cell, through pores called plasmodesmata .Bacteria, like plants, have strong cell walls that a virus must breach to infect the cell. Some viruses have evolved mechanisms that inject their genome into the bacterial cell while the viral capsid remains outside.
bulletUncoating is a process in which the viral capsid is degraded by viral enzymes or host enzymes thus releasing the viral genomic nucleic acid.
bulletReplication involves synthesis of viral messenger RNA (mRNA) for viruses except positive sense RNA viruses, viral protein synthesis and assembly of viral proteins and viral genome replication.
bulletFollowing the assembly of the virus particles, post-translational modification of the viral proteins often occurs. In viruses such as HIV, this modification (sometimes called maturation) occurs after the virus has been released from the host cell.
bulletViruses are released from the host cell by lysis—a process that kills the cell by bursting its membrane. Some viruses undergo a lysogenic cycle where the viral genome is incorporated by genetic recombination into a specific place in the host's chromosome. The viral genome is then known as a "provirus" or, in the case of Bacteriophages a "prophage".Whenever the host divides, the viral genome is also replicated. The viral genome is mostly silent within the host, however, at some point, the provirus or prophage may give rise to active viruses, which lyse their host cells. Enveloped viruses (e.g., HIV) typically are released from the host cell by budding. During this process the virus acquires its envelope, which is a modified piece of the host's plasma membrane.


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Effects on the host cell

The range of structural and biochemical effects that viruses have on the host cell is extensive. These are called cytopathic effects. Most virus infections eventually result in the death of the host cell. The causes of death include cell lysis, alterations to the cell's surface membrane and apoptosis. Often cell death is caused by cessation of its normal activities because of suppression by virus-specific proteins, not all of which are components of the virus particle.

Some viruses cause no apparent changes to the infected cell. Cells in which the virus is latent and inactive show few signs of infection and often function normally. This causes persistent infections and the virus is often dormant for many months or years. This is often the case with herpes viruses. Some viruses, such as Epstein-Barr virus, can cause cells to proliferate without causing malignancy, while others, such as papillomaviruses, are established causes of cancer.

Host range

Viruses are by far the most abundant parasites on earth and they have been found to infect all types of cellular life including animals, plants and bacteria. However, different types of viruses can only infect a limited range of hosts and many are species-specific. Some, such as smallpox virus for example, can only infect one species—in this case humans, and is said to have a narrow host range. Other viruses, such as rabies virus, can infect different species of mammals and is said to have a broad range. The viruses that infect plants are harmless to animals and most viruses that infect other animals are harmless to humans. The host range of some Bacteriophages is limited to a single strain of bacteria and they can be used to trace the source of outbreaks of infections by a method called phage typing.

Overview of the main types of viral infection and the most notable species involved.

Examples of common human diseases caused by viruses include the common cold, influenza, chickenpox and cold sores. Many serious diseases such as Ebola, AIDS, avian influenza and SARS are caused by viruses. The relative ability of viruses to cause disease is described in terms of virulence. Other diseases are under investigation as to whether they too have a virus as the causative agent, such as the possible connection between human herpes virus six (HHV6) and neurological diseases such as multiple sclerosis and chronic fatigue syndrome. There is controversy over whether the borna virus, previously thought to cause neurological diseases in horses, could be responsible for psychiatric illnesses in humans.

Viruses have different mechanisms by which they produce disease in an organism, which largely depends on the viral species. Mechanisms at the cellular level primarily include cell lysis, the breaking open and subsequent death of the cell. In multicellular organisms, if enough cells die the whole organism will start to suffer the effects. Although viruses cause disruption of healthy homeostasis, resulting in disease, they may exist relatively harmlessly within an organism. An example would include the ability of the herpes simplex virus, which causes cold sores, to remain in a dormant state within the human body. This is called latency and is a characteristic of the herpes viruses including Epstein-Barr virus, which causes glandular fever, and varicella zoster virus, which causes chickenpox. Most people have been infected with at least one of these types of herpes virus. However, these latent viruses might sometimes be beneficial, as the presence of the virus can increase immunity against bacterial pathogens, such as Yersinia pestis. On the other hand, latent chickenpox infections return in later life as the disease called shingles.

Some viruses can cause life-long or chronic infections, where the viruses continue to replicate in the body despite the host's defense mechanisms. This is common in hepatitis B virus and hepatitis C virus infections. People chronically infected are known as carriers, as they serve as reservoirs of infectious virus. In populations with a high proportion of carriers, the disease is said to be endemic. In contrast to acute lytic viral infections this persistence implies compatible interactions with the host organism. Persistent viruses may even broaden the evolutionary potential of host species.

 

Epidemics and pandemics

Transmission electron microscope image of a recreated 1918 influenza virus

Native American populations were devastated by contagious diseases, particularly smallpox, brought to the Americas by European colonists. It is unclear how many Native Americans were killed by foreign diseases after the arrival of Columbus in the Americas, but the numbers have been estimated to be close to 70% of the indigenous population. The damage done by this disease significantly aided European attempts to displace and conquer the native population.

A pandemic is a worldwide epidemic. The 1918 flu pandemic, commonly referred to as the Spanish flu, was a category 5 influenza pandemic caused by an unusually severe and deadly influenza A virus. The victims were often healthy young adults, in contrast to most influenza outbreaks, which predominantly affect juvenile, elderly, or otherwise weakened patients.

The Spanish flu pandemic lasted from 1918 to 1919. Older estimates say it killed 40–50 million people, while more recent research suggests that it may have killed as many as 100 million people, or 5% of the world's population in 1918.Most researchers believe that HIV originated in sub-Saharan Africa during the twentieth century; it is now a pandemic, with an estimated 38.6 million people now living with the disease worldwide. The Joint United Nations Programme on HIV/AIDS (UNAIDS) and the World Health Organization (WHO) estimate that AIDS has killed more than 25 million people since it was first recognized on June 5, 1981, making it one of the most destructive epidemics in recorded history. In 2007 there were 2.7 million new HIV infections and 2 million HIV-related deaths.

 
Marburg virus

Several highly lethal viral pathogens are members of the Filoviridae. Filoviruses are filament-like viruses that cause viral hemorrhagic fever, and include the Ebola and Marburg viruses. The Marburg virus attracted widespread press attention in April 2005 for an outbreak in Angola. Beginning in October 2004 and continuing into 2005, the outbreak was the world's worst epidemic of any kind of viral hemorrhagic fever.

Vaccines

Vaccination is a cheap and effective way of preventing infections by viruses. Vaccines were used to prevent viral infections long before the discovery of the actual viruses. Their use has resulted in a dramatic decline in morbidity (illness) and mortality (death) associated with viral infections such as polio, measles, mumps and rubella. Smallpox infections have been eradicated. Vaccines are available to prevent over thirteen viral infections of humans, and more are used to prevent viral infections of animals. Vaccines can consist of live-attenuated or killed viruses, or viral proteins (antigens). Live vaccines contain weakened forms of the virus, which do not cause the disease but nonetheless confer immunity. Such viruses are called attenuated. Live vaccines can be dangerous when given to people with a weak immunity, (who are described as immuno-compromised), because in these people, the weakened virus can cause the original disease. Biotechnology and genetic engineering techniques are used to produce subunit vaccines. These vaccines use only the capsid proteins of the virus. Hepatitis B vaccine is an example of this type of vaccine. Subunit vaccines are safe for immuno-compromised patients because they cannot cause the disease. The yellow fever virus vaccine, a live-attenuated strain called 17D, is probably the safest and most effective vaccine ever generated.

Antiviral drugs

Over the past twenty years, the development of antiviral drugs has increased rapidly. This has been driven by the AIDS pandemic. Antiviral drugs are often nucleoside analogues, (fake DNA building blocks), which viruses incorporate into their genomes during replication. The life-cycle of the virus is then halted because the newly synthesized DNA is inactive. This is because these analogues lack the hydroxyl groups, which, along with phosphorus atoms, link together to form the strong "backbone" of the DNA molecule. This is called DNA chain termination. Examples of nucleoside analogues are aciclovir for Herpes simplex virus infections and lamivudine for HIV and Hepatitis B virus infections. Aciclovir is one of the oldest and most frequently prescribed antiviral drugs. Other antiviral drugs in use target different stages of the viral life cycle. HIV is dependent on a proteolytic enzyme called the HIV-1 protease for it to become fully infectious. There is a large class of drugs called protease inhibitors that inactivate this enzyme.

Hepatitis C is caused by an RNA virus. In 80% of people infected, the disease is chronic, and without treatment, they are infected for the remainder of their lives. However, there is now an effective treatment that uses the nucleoside analogue drug ribavirin combined with interferon. The treatment of chronic carriers of the hepatitis B virus by using a similar strategy using lamivudine has been developed.

Infection in other species

Viruses infect all cellular life and, although viruses occur universally, each cellular species has its own specific range that often infect only that species. Some viruses, called satellites, can only replicate within cells that have already been infected by another virus. Viruses are important pathogens of livestock. Diseases such as Foot and Mouth Disease and bluetongue are caused by viruses. Companion animals such as cats, dogs, and horses, if not vaccinated, are susceptible to serious viral infections. Canine parvovirus is caused by a small DNA virus and infections are often fatal in pups. Like all invertebrates, the honey bee is susceptible to many viral infections. Fortunately, most viruses co-exist harmlessly in their host and cause no signs or symptoms of disease.

 

Role in evolution

Viruses are an important natural means of transferring genes between different species, which increases genetic diversity and drives evolution. It is thought that viruses played a central role in the early evolution, before the diversification of bacteria, archaea and eucaryotes and at the time of the last universal common ancestor of life on Earth. Viruses are still one of the largest reservoirs of unexplored genetic diversity on the Earth.

Weapons

The ability of viruses to cause devastating epidemics in human societies has led to the concern that viruses could be weaponised for biological warfare. Further concern was raised by the successful recreation of the infamous 1918 influenza virus in a laboratory. The smallpox virus devastated numerous societies throughout history before its eradication. There are officially only two centers in the world which keep stocks of smallpox virus—the Russian Vector laboratory, and the United States Centers for Disease Control. But fears that it may be used as a weapon are not totally unfounded; the vaccine for smallpox is not safe—during the years before the eradication of smallpox disease more people became seriously ill as a result of vaccination than did people from smallpox — and smallpox vaccination is no longer universally practiced. Thus, much of the modern human population has almost no established resistance to smallpox.