Influenza: Diagnosis, Treatment, Prevention - V.D. Moskaliuk 2010

Influenza
Variability and Evolution of Influenza Viruses

Thus, there are three independent types of Influenza Viruses: A, B, and C. They belong to the Orthomyxoviridae family and share a characteristic Structure, meaning they are all built on the same fundamental principle. Externally, the viral particle is covered by a protein envelope primarily composed of protruding spikes that form a sort of viral 'passport.' These are the so-called envelope Antigens of the influenza virus: hemagglutinin (HA) and neuraminidase (NA). Their ratio on the viral surface is 3:1. It has now been scientifically proven that hemagglutinin plays the decisive role in The Development of the INFECTION AND ITS epidemic spread.

The outer envelope protects the central core of the virus—the nucleocapsid, which is represented by a spirally twisted ribonucleic acid (RNA) chain covered with an inner layer of protein molecules. This is the viral genome, its Replication mechanism, which hereditarily transmits all The properties of the disease-causing agent. The Genome consists of 8 fragments, distinct RNA segments that program The formation of the viral particle. Each Gene is responsible for the synthesis of a corresponding protein. Viral genes and Proteins share the same names and are designated by Latin letters; therefore, specialized scientific literature employs such symbols as the genes PB1, PB2, CA, NP, HA, M, and NS. Each of them performs a specific function related to the synthesis of RNA and proteins.

Despite this complex structure, the influenza virus is exceptionally small in size and can only be seen under an Electron microscope at a magnification of 300,000–500,000 times.

It would seem that The structure of the virus and the Functions of its individual components have been studied to a sufficient degree. What happens in the Organism after the virus penetrates the Cells is also known; however, the mysteries surrounding The Nature of the influenza virus have not diminished. What is the reason for this? The fact is that this virus possesses an extremely unique property: it is constantly changing. Incidentally, not all of its components change, but only the surface antigen proteins, HA and NA.

To better understand the nature of influenza virus Variability, let us examine the scheme of its evolution over the years since the pathogen was discovered.

In 1933, the first influenza virus was isolated, designated by the symbols of its antigenic proteins: virus A (H0N1), where H0 stands for zero-type hemagglutinin and N1 for first-type neuraminidase.

Subsequent in-depth studies of pathogens isolated in various years across different countries revealed that influenza viruses differ in their hemagglutinin and neuraminidase composition. It has been established that there are 11 types of hemagglutinin and 8 types of neuraminidase. Human influenza viruses contain hemagglutinin of the first, second, and third types, and neuraminidase of only the First and Second types. Avian influenza viruses possess hemagglutinin of the fourth through sixth, and eighth through eleventh types, and neuraminidase of the third through sixth types; animal influenza viruses feature seventh-type hemagglutinin, and seventh- and eighth-type neuraminidase.

It is now proven that A change in the hemagglutinin or neuraminidase type (from the first to the second or third) is accompanied by the development of a pandemic. This phenomenon of drastic antigenic shift is termed a "shift."

Thus, the first pandemic of the 20th century was caused by the A (H0N1) virus; the second (1947–1948) featured a mutated pathogen in which zero-type hemagglutinin was replaced by first-type hemagglutinin; the third pandemic (1957–1958) was triggered by a new virus type with both antigens renewed—both hemagglutinin and neuraminidase—namely, A (H2N2); and the most recent pandemic (1968–1969) was caused by yet another novel pathogen: the A (H3N2) virus.

Thus, over the more than 50 years since the Discovery of the influenza virus, there have been 4 complete replacements of the influenza pathogen. With The Emergence of a new generation, all predecessors generally disappeared completely from the epidemic cycle, yet persisted as so-called "relict" forms that caused sporadic cases or minor disease outbreaks.

During interpandemic periods, epidemic waves of influenza—caused by the virus responsible for the pandemic—originated and subsided almost annually. However, it has been observed that each epidemic is driven by a virus that partially differs from its predecessor but generally remains within the framework of the shifted variant known as the virus serotype.

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Fig. 1. Cytology/cytology/92.html">SCHEMATIC STRUCTURE OF the influenza virus.

The phenomenon of partial alteration in hemagglutinin and neuraminidase is termed "drift." For example, in 1969, the A (H3N2) virus emerged globally. It originated in Southeast Asia (China), although the pathogen was first isolated in Hong Kong. Consequently, the virus received a name reflecting its origin: influenza virus A (Hong Kong) 68 (H3N2). This name indicates the virus type (influenza virus A), THE PLACE OF isolation (Hong Kong), its structural makeup (H3N2), and the year of origin (68). This virus circulates to this day. It has undergone a series of alterations, forming distinct serosubtypes that share similar antigens in their envelopes. The A (Hong Kong) 68 virus circulated without visible changes until 1972, followed by the A (England) 72 virus, then A (Port Chalmers) 73, A (Victoria) 75, A (Texas) 77, and A (Bangkok) 79. Currently, the prevalent strain features the antigenic STRUCTURE OF THE Philippine variant: A (Philippines) 83. What compels the influenza virus to change constantly, and what is the underlying reason?

It turns out that during the epidemic process, the influenza virus alters the antigenic structure of its hemagglutinin and neuraminidase in order to survive as a biological species. Because the influenza virus simultaneously infects a vast number of people, Immunity typically develops in everyone During the first few years following a pandemic—meaning Antibodies appear in the Blood that protect the organism from the virus's effects. Therefore, the influenza pathogen must adapt to these antibodies so they do not hinder the development of infection in The Human Body. To achieve this, it is sufficient for the virus to slightly modify its envelope structure. Despite the presence of antibodies in the blood, the pathogen once again becomes capable of causing disease.

The mechanisms of drift and shift are not yet fully understood, making it impossible to predict every subsequent viral mutation; consequently, the fight against influenza has not yet yielded the desired outcomes.

It must be noted that among all studied influenza pathogens, virus A is the most active, while virus C is the least active (causing illness primarily in young children). The nature of influenza virus variability has essentially become one of the most pressing issues in combating this disease, and solving it will provide the key to unraveling the fundamental secret of the influenza pathogen: the mechanism that leads to the partial or complete alteration of the surface antigens on its envelope.

It also remains unknown where influenza viruses are preserved during interpandemic periods (in spring, summer, and autumn) when there are no influenza patients. This question has long concerned epidemiologists, as the answer will shed light on other equally crucial matters: how pandemic influenza viruses are generated and why new pathogen variants form.

Today, scientists hold two viewpoints regarding the preservation site of the influenza virus. Some believe that humans alone constitute its permanent source (reservoir). Through direct interaction between the virus and a human—whose blood contains anti-influenza antibodies—a Selection occurs of those viruses that, through adaptation, have altered their antigenic properties and regained aggressiveness. All of this takes place exclusively within the human body. Proponents of this view maintain that human influenza viruses represent an independent family of viruses related in their properties to avian and animal influenza viruses.

It turned out that influenza viruses have many "relatives," the closest being the swine influenza virus. Interestingly, during the era when the influenza virus was still unknown, Pfeiffer's bacillus was credited with The ability to cause influenza in swine. Detailed studies of influenza epidemics among these animals demonstrated a close relationship between the swine influenza virus and the human A (H0N1) virus, although they remain separate, independent influenza virus strains. They differ in their hemagglutinin; thus, the swine influenza pathogen entered science as a distinct serotype, A (HSWN1), where the designation SW derives from the Latin word "swine."

Some veterinarians believe that pigs can contract infections from humans. Outbreaks of influenza on pig farms have repeatedly been recorded after service personnel fell ill. The reverse phenomenon (humans contracting the infection from pigs) has not been observed to date. Despite this, the swine virus was recognized as the pathogen responsible for the 1918–1919 Spanish flu pandemic. Blood tests of individuals who suffered from influenza in 1918–1920 revealed antibodies against the HSW-type hemagglutinin—that is, the swine virus. Humanity encountered this virus once more in 1976. When the A (N3N2) virus—descended from the A (Hong Kong) 68 virus—spread globally, an influenza outbreak erupted at a military base in New Jersey (USA), and an influenza virus with hemagglutinin related to that of the A (NSWN1) virus was isolated from patients. Blood serum screenings revealed about 500 individuals infected with this virus. Concerns arose regarding a potential recurrence of the Spanish flu, and the US government decided to develop a prophylactic vaccine. Yet the unexpected occurred: the epidemic did not spread beyond the town of New Jersey, and all manufactured Vaccines proved unnecessary. In the opinion of Soviet scientists, this was a swine virus that failed to establish itself in the human organism, which limited its dissemination.

Avian and equine influenza viruses have been thoroughly studied, but they have never held epidemic significance for humans. For instance, fowl plague is a long-known disease that, upon closer examination, turned out to be avian influenza, caused by a virus similar to the human influenza A virus. However, humans do not contract this ailment and cannot be infected by chickens. All these viruses differ from human viruses primarily in their envelope structure and antigens, which are unique to animal or avian viruses. Not a single epidemic or even an outbreak of influenza caused by avian or equine viruses has ever been described. At the same time, it has been proven that domestic animals and birds can be infected by a sick human and contract influenza.

The interrelations between human, animal, and avian influenza viruses are studied by scientific ecology. Special Laboratory studies have demonstrated that human influenza can be transmitted to dogs, pigs, calves, wild birds, and so forth. This proposition formed the basis for developing the second hypothesis regarding THE ORIGIN OF influenza viruses. Its proponents argue that animals and birds may serve as a natural reservoir for various Variants of the influenza A virus, which was once widespread among humans. It is worth adding, incidentally, that this applies to virus A; no such data exist for viruses B and C.

The most compelling evidence for this hypothesis came from discoveries that caused a scientific sensation just a few years ago: human influenza viruses—or rather, certain of their constituent components—were found in camels in the Mongolian desert, wild migratory birds in the Far North, whales, dolphins, and so on. Evidently, a continuous exchange of genes occurs in nature between human, animal, and avian viruses. This exchange leads to the emergence of new antigenic variants of the influenza virus. The Spanish flu was likely caused by precisely such a virus—a hybrid of swine and human viruses. Later, as immunity against this virus formed among humans due to prior infection, the number of "victims" dropped sharply, and the virus gradually lost the host in which it could reproduce and survive. The Spanish flu virus vanished, ceasing to exist, but it left behind its counterpart: the swine influenza virus.

Such a counterpart was also found for another virus: A (Hong Kong) 68. This is a duck influenza virus, similar to the human strain yet not identical to it. Consequently, the Conclusion is drawn that the source of the Hong Kong virus variant should be sought among avian species.

Researchers who disagree with this hypothesis believe that human influenza viruses have their own clearly defined gene composition and do not require any animal or avian additions. In their opinion, the number of these viruses is limited; they re-infect the population every 30–80 years, precisely when a new generation of people grows up whose blood lacks antibodies against them.