The Evolution of Influenza Virus A

The Origins of Virology

A virus is an infectious agent that exists within other living organisms. Viruses may be found in human beings, animals, plants, and even bacteria. The word “virus” is Latin and denotes poison. The use of the term “virus” to denote the biological cause of infectious disease began in the early eighteenth century (Koonin, Senkevich, & Dolja, 2006). However, viruses in the sense of the contemporary meaning of the term were discovered in 1892 by Dmitri Ivanovsky. Speculation about possible pathogenic causes of disease began in the middle to the late nineteenth century (Breitbart & Rohwer, 2005). The famous French scientist Louis Pasteur believed that rabies was caused by an infectious agent that would be too tiny to be observed through the use of a microscope (Bordenave, 2003). Another French scientist, Charles Chamberland, developed a kind of filter that was able to remove bacteria from liquid solutions. Ivanovsky subsequently used this filter to isolate and identify the “tobacco mosaic virus.” At the time, it was believed that germs were the cause of disease. A Dutch scientist by the name of Martinus Beijerinck subsequently identified viruses as a previously undiscovered form of disease-causing agent in 1898.

Scientific knowledge concerning viruses continued to expand during the early twentieth century. Frederick Twort and Felix d’Herelle discovered “bacteriophages,” or forms of viruses that would infect and kill bacteria. A number of other scientists began to experiment with the growth of viruses in plant and animal tissue for experimental purposes. Research of this type became particularly important as greater investigation into the possibility of a vaccine for polio was pursued (Edwards & Rohwer, 2005). The American scientist Ernest William Goodpasture began to grow the influenza virus in chicken eggs in 1931 (Goodpasture, Woodruff & Buddingh, 1931). A group of American scientists subsequently began to grow the poliovirus in actual human embryos, and this research led to the development of the vaccination for polio discovered by Jonas Salk.

The German scientists Max Knoll and Ernst Ruska also began to use the electron microscope to produce images of viruses in 1931 (Rybicki, 1990). Wendell Meredith Stanley studied the tobacco mosaic virus and was able to separate the virus into two parts, RNA and protein (Stanley & Loring, 1936). This was also the first virus where its structure could be thoroughly determined. In 1955, Heinz Fraenkel Conrat and Robley Williams determined that functional viruses in living organisms were able to create themselves through a natural hybrid of virus RNA and protein coating. It was recognized that viruses transmit themselves in this way. Throughout the remainder of the twentieth century, more than two thousand new viruses were discovered. Among these were viruses that were identified as the causes of bovine diarrhea and hepatitis B. Retroviruses were discovered in 1965 when it was determined that these viruses use the enzyme reverse transcriptase to replicate their RNA into DNA reproductions. The retrovirus HIV was discovered in 1983 to be the cause of AIDS.

The Classification of Viruses

Since their initial discovery, the ongoing identification of different viral forms has resulted in their being classified into a system of taxonomic categories. The system for the taxonomic classification of viruses displays a great similarity to the one used for the classification of cellular organisms. However, the taxonomic system for virus classification is less precise than its counterpart (Prangishvili & Krupovic, 2012). The difficulty involved is that viruses are not fully living organisms. Instead, they may be said to be a kind of hybrid of organic and chemical materials. The primary method that is utilized to classify viruses involves the identification of their phenotype characteristics. Characteristics of these kinds demonstrated by viruses include their methods of self-replication, morphology, host organisms, nucleic acids, and the variations in the kinds of diseases they cause.

At present, there are two primary virus classification systems. One of these has been developed by the International Committee on Taxonomy of Viruses (ICTV). The other is the Baltimore classification system. The ICTV defines a virus species as a particular class of viruses that maintain their own reproductive line, and which can be found in a specific niche within eco-systems. Virus classification is done on several different successive levels including order, family, subfamily, genus, and species. At the species level, viruses are classified on the basis of the diseases with which they are associated. Currently, the ICTV identifies seven orders, ninety-six families, twenty-two subfamilies, four hundred and twenty genus variations, and two thousand six hundred and eighteen species variations. There are currently seven categories of species (Prangishvili & Krupovic, 2012). Tymovirales are viruses that infect plants. Nidovirales infect vertebrate hosts. Picornvirales infect plant, animal, and insect hosts. Mononegavirales infect plants and animals. Caudovirales are bacteriophages. Herpesvirales include eukaryotic dsDNA viruses, and Ligamenvirales contain dsDNA archaean viruses.

The Baltimore classification system was developed by the Nobel Laureate Dr. David Baltimore (Hall, 1991). The Baltimore system likewise has seven distinctive categories of virus classification. Group one includes double-stranded DNA viruses such as herpesviruses, poxviruses, and adenoviruses. Group two are single-stranded DNA viruses that include parvoviruses, circoviruses, anelloviruses, geminiviruses, and nanoviruses. Group three are double-stranded RNA viruses including reoviruses and birnaviruses. Groups four and five include single-stranded RNA viruses. These viruses may be either positive or negative, and replicate themselves in the cytoplasm. Group six are positive single-stranded RNA viruses that reproduce through a DNA intermediate. Retroviruses are included in this category. Group seven are double-stranded DNA viruses that reproduce through a single-stranded RNA intermediate. An example is the hepatitis B virus.

Viruses by Species

Many human diseases and illness care caused by viruses (Leppard, Nigel, & Easton, 2007). Some of the more prominent or well-known of these include cold sores, chickenpox, influenza, common colds, ebola, avian influenza, SARS, and AIDS. The degree to which a virus will be able to cause disease in humans is largely dependent on the virulence of the particular virus in question. It is also widely suspected in the scientific community that other diseases such as chronic fatigue syndrome, human herpesvirus 6, and multiple sclerosis may be caused by viruses. It is also debated as to whether the bonavirus may be a source of mental illness in humans. Some viruses, such as herpes simplex, may remain dormant in the human body. Epstein Barr virus may also remain dormant in the body, and later erupt to cause such illnesses as glandular fever. Most people carry some form of a virus in the body, and some people are carriers of more serious viruses, such as those associated with hepatitis B and hepatitis C.

Viruses may be transmitted in humans from either mother to child in a hereditary sense, or through person to person contact (Leppard, et. al., 2007). Examples of the former, known as vertical transmission, include the transmission of either hepatitis or HIV from a mother to her offspring. Examples of the latter, known as horizontal transmission, are widely divergent. They include transmission of viruses through transfusions using contaminated blood, the sharing of needles, the exchange of body fluids through sexual activity, contaminated food and water, insect bites, the exchange of saliva, or the inhaling of aerosols. The transmission of viruses is most common in environments where there is a large population, unsanitary living conditions, poor healthcare and preventive medicine, tropical weather, and where the susceptibility of individuals to viral infection is high.

Some populations also give the appearance of being more susceptible to viral infections than others. It has been estimated that approximately seventy percent of the Native American population of North America succumbed to smallpox during the time of the arrival of the European settlers in the early seventeenth century. There was an international pandemic of a particularly strong strand of influenza A virus in 1918 (Taubenberger & Morens, 2006). Often those who succumbed to the virus appeared to be otherwise healthy and relatively young adults. It has been estimated that approximately one hundred million people, about five percent of the world’s population at the time, actually died from this particular outbreak of influenza. Another such pandemic generated by a virus has been the prevalence of AIDS, caused by the human immunodeficiency virus (HIV), since the disease was first discovered in 1981. It has been estimated that approximately twenty-five million people have died from AIDS.

In recent decades, medical researchers have become increasingly aware of the role of viruses in the development of cancers in humans (Hausen, 2008). Only a minority of persons infected with cancer viruses will actually develop cancer. Cancer viruses may be of both the DNA and RNA variety. There is no one single cancer-causing virus in human beings. Those viruses which are believed to cause cancer in humans include human T-lymphotropic virus, Kaposi’s sarcoma herpesvirus, human papillomavirus, both hepatitis B and hepatitis C viruses, and Epstein Barr virus (Klein, Kis, & Klein, 2007). Merkel cell polyomavirus may cause skin cancer (Shuda, Feng, Kwun, Rosen, Gjoerup, Moore & Chang, 2008). Hepatitis may cause the infected person to develop liver cancer. Human T-lymphotropic virus may cause leukemia, particularly among adults. Papillomaviruses may cause a variety of cancers in human beings, including those of the anal tract, skin, penis, and cervix.

The human body primarily fights infections by viruses through the natural immune system. One of the major components of this natural defense system is RNA interference (Leppard, et. al. 2007). Biochemical pathways become activated that break down the viral mRNA and help to promote cell survival. The immune system produces natural antibodies that ward off infectious agents when viruses are detected. Some natural antibodies are very effective at countering infectious viral agents but do not have much longevity. Other forms of antibodies have a much longer life span. Even after an organism has been infected antibodies can still be operative. Proteins may grow in cells that have the effect of destroying the virus as it grows parasitically upon a cellular organism. Infectious viral agents may also be combated through the use of vaccinations and antiretroviral drugs.

Many viruses are only able to infect certain species, and sometimes only one species (Leppard, et. al., 2007). Among animal species, viruses may impact vertebrate and invertebrate species differently. Humans are not susceptible to plant and insect viruses. However, they may be able to acquire some viruses affecting vertebrate animals such as rabies and yellow fever. Some vertebrate animals seem especially susceptible to certain viruses. For instance, rabbits are particularly vulnerable to myxomatosis. Ordinary household animals may also become infected by viral agents. It is for this reason that pet owners will often have their dogs, cats, and the like vaccinated against serious diseases. Dogs are particularly susceptible to parvovirus. Cats are most at risk of being infected by feline leucopenia.

Invertebrates differ from vertebrates in that their immune systems do not produce antibodies, but they do have immune systems of their own. Some invertebrates appear to have a natural immunity to some viral infections. One the other hand, some species such as the honey bee seem to have a high level of susceptibility to many kinds of viruses in a way that is potentially able to upset ecological balance (Fraile & García-Arenal, 2010). The best-known categories of viruses that infect invertebrates are baculoviruses. These viruses are recognized for their lethal effects on many kinds of insects that threaten agricultural plants, and some pesticide materials are derived from these viruses.

Viruses can also infect plants, and there are many different viruses of these kinds to which plants are susceptible (Fraile et al., 2010). Plant viruses are often spread by means of vectors. The most common vectors are certain kinds of insects. Other vectors include fungi, worms, and even some single-celled organisms. Viruses that are specific to plants do not infect humans or animals. There are also other viruses that primarily affect bacteria. The most common of these are bacteriophages and are usually found in water environments. They attach themselves to surface receptor molecules and invade cells in this manner. Bacteria also produce enzymes that have the effect of destroying infectious DNA. Bacteria may also develop a genetic immunity to viral infection. The most common kinds of viruses that affect the archaea are unusually shaped DNA viruses that are also double-stranded. RNA interference is the most effective means of resistance to infection for archaea.

The Evolution of Viruses

Viruses do not leave behind a fossil record, so it is impossible to use the ordinary techniques of paleontology to identify their origins. Instead, the study of the origins of viruses is oriented primarily towards the use of molecular techniques (Smith, Lapedes, De Jong, et. al. 2004). There are three primary hypotheses concerning the origins of viruses. The regressive hypothesis speculates that viruses were once smaller cells than evolved into larger cells through parasitism. Once the non-parasitical genes of these viruses disappeared, the virus structures began to take on a life of their own. A comparison is sometimes made to the bacteria causing the sexually transmitted disease Chlamydia, which replicates itself within its own host organism (Horn, 2008). There is also a cellular origins hypothesis which suggests that viruses are perhaps rooted in strands of DNA or RNA that were released from their wider organism’s genetic structure. It is normally believed by virologists that viruses have most likely existed as long as cells have been in existence. Out of this observation, a co-evolution hypothesis has emerged. According to this hypothesis, both cells and viruses likely emerged from protein nucleic acids at approximately the same time, and have to some degree been co-dependent on each other in the process of the evolution of both.

The foundations of contemporary evolutionary theory regarding viruses are derived from the study of viral genomes. Viruses will normally experience evolution through changes in their RNA or DNA. Natural selection plays a key role in the evolution of viruses. The methods by which viruses reproduce within their host organisms will enhance their genetic evolution. Viruses rooted in RNA display a much greater capacity for undergoing a rapid mutation and evolutionary process than their DNA-based counterparts. Mechanisms exist within viruses that assist in the correction of mistakes pertaining to the process of reproduction. Consequently, lethal mutations are not passed to offspring nearly as frequently. However, when an RNA virus reproduces in its host cell lethal genetic errors may occur. Most mutations of viruses do not adversely affect their offspring. Still others enhance the adaptability of the virus in question. Viruses also have the effect of transferring genes between species (Leppard, et.al.,2007). This, in turn, contributes to genetic diversity and helps to drive the process of the biological evolution of species.

Influenza Virus A

The influenza virus A is the cause of influenza in varying species of mammals. It is also the cause of influenza among birds. There is only one variation of influenza virus A, and it is a genus of the family of viruses known as Orthomyxoviridae. However, there are subtypes of this particular virus, and strands of these varying subtypes have been identified among different species of birds. Influenza virus A is particularly known for causing serious diseases among poultry. Humans can also be infected with these diseases as well (Tang, Shetty, Lam & Hon, 2010). On occasions when influenza virus A contributes to an outbreak of influenza among humans, the normal process of this occurring involved the transfer of the virus from wild birds that inhabit wet climates to poultry and then to human beings.

Influenza virus A is negative, RNA-based, and single-stranded. Its subtypes are categorized according to the presence of hemagglutinin (H) or neuraminidase (N). There are eighteen forms of H and eleven forms of N. Two of the eighteen forms of H were discovered in the last two years. In 2012, H17 was found among fruitbats. In 2013, H18 was found among another species of bat in Peru. Each particular variation of influenza virus A has mutated during the course of its existence. These different strands and subtypes will often cause disease in only one known species. Others will cause disease in some species but not in others (Leppard, et. al. 2007). The most common form of the disease among humans that is caused by influenza virus A is avian influenza, caused by avian feces, and also known as the “bird flu.”

The differences between H and N have to do with a particular protein and a particular enzyme. H involves a protein that affects red blood cells while N is an enzyme that attaches the glycosidic bonds of the neuraminic acid. Variations among the different kinds of influenza virus A are often labeled according to the primary species which they impact. Not only is there the aforementioned “bird flu,” but there is also swine influenza, equine influenza, canine influenza, and human influenza (De Jong, Bach & Phan, 2005). The pathogenic qualities of different strands of influenza virus A can also differ significantly. Some may have a lethal effect on their hosts and others may not. Some strands of influenza virus A are believed to now be extinct. For example, the form of influenza once referred to as the “Asian flu” or the “Hong Kong flu” has not been identified for some time and is now believed to no longer be in existence. However, human influenza still presents serious health challenges to human beings (Tweed, Skowronski & David, 2004). In the United States alone, there are over thirty-six thousand deaths per year from human influenza and over two hundred thousand more incidents of hospitalization at the cost of ten billion dollars per year.

The influenza virus A is very similar in its structure and genetics to types B and C of the influenza virus. The size of the virus itself is approximately eighty to one hundred nanometers and it is round-shaped. The genome for influenza virus A has over thirteen thousand bases. On approximately twenty occasions in the past half-century, particularly toxic forms of influenza virus A have been identified among poultry as the result of widespread outbreaks. Studies of the ongoing evolution of influenza virus A have shown slow but random change to be the guiding evolutionary processes.

The Evolution of Influenza Virus A

A unique feature of the influenza A virus is the rapid nature of its ongoing evolution. It is for this reason that an effective vaccine for influenza A virus is difficult to develop and maintain. Many other diseases for which there are effective vaccinations are caused by infectious agents that evolve much more slowly (Wang & Palese, 2011). Yet influenza A virus evolves very quickly even within the span of a single year, or even a single season. The antibodies in the body generated by vaccination are therefore unable to recognize the strands of the new variation of influenza virus A as they infect the body. In fact, it is in part through the exposure to human antibodies that the virus continues to evolve. This aspect of the evolutionary process is called antigenic drift. Particles of a flu virus containing mutations undergo natural selection whereby they are able to evade the anti-influenza antibodies. These more potent strains of influenza virus that have evaded the antibodies will then reproduce themselves, and go on to infect a wider number of people (Nabel & Fauci, 2010). New strands of the virus will then emerge, and these new strands will produce yet another cyclical outbreak of influenza.

The most frequent means by which the virus evolves are reassortment and genetic drift (Liu, Kang, et.al. 2009). The process of reassortment means that influenza virus A will be able to develop in both a natural environment and in an environment that is artificially simulated. The pathogenic qualities of a strand of a virus can evolve in such a way that the virus will infect some species but not others. Genetic drift involves a process where the mutation and natural selection process affecting a particular virus favor the strongest strand of the pathogen. However, drift can also be antigenic in nature. This usually involves a very high rate of mutation. A single cell will be infected by two influenza A viruses. This strengthens their resistance to antibodies (Scholtissek, 1995). Exposure to antibodies then strengthens the virus itself and enhances its evolutionary process.

The process of transmitting influenza A virus between species is more difficult. Human beings and birds cannot transmit the virus across species lines, but pigs may transmit the virus to humans. The methods by which the virus is transmitted, and transmitted along inter-species lines, may also vary according to differences in geography. The virus is more likely to be transmitted in some geographical areas than in others. For instance, the transmission of influenza virus A to humans appears to be particularly common in Southeast Asia. There is also evidence that the variations in the influenza virus have a common ancestor. The primary types of influenza virus are simply labeled as A, B, and C. The first types are causes of regular seasonal epidemics of influenza (CDC, 2014). Influenza virus C causes respiratory illness in humans, but this form of influenza normally does not result in an epidemic.

The process of infection by the influenza A virus includes multiple stages (Nabel & Fauci, 2011). The virus is usually acquired by the human body by means of entry through the mouth or nose membrane. The virus will then take root in the lungs and being to grow. This will happen within a few days after the initial infection. The infected person then becomes contagious. A fever will develop, and the infected person will experience shivers, headaches, and aching muscles. Breathing also becomes more difficult. A sore throat and a cough will normally develop as well. Usually, the process of infection lasts about nine to ten days.

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