Influenza A Evolution And Transmission Biology Essay

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Influenza commonly called flu is an illness that caused by a virus that infects the respiratory tract, the nose, throat and bronchi and rarely also the lungs.

It is caused by RNA viruses of the family orthomyxoviridae that affects birds and mammals. It also has the ability to cause pandemic infection in humans.

Influenza A virus was the first to be isolated in 1933 by intranasal inoculation of the ferret. Thereafter type B was isolated along with type A in cell culture in 1940.

One of the most prominent features of influenza viruses is their ability to change antigenically either by antigenic shift or antigenic drift. Influenza virus it is not a cause of low fever and sniffles that keeps you home in bed and it is not a gastrointestinal upset (stomach flu).

Influenza A results in high mortality and morbidity rates in man in the winter months in temperature zone, but throughout the year in more tropical climates. Since 1997, avian influenza has been a major problem in the Far East, with strains from domestic poultry occasionally infecting individual directly, resulting in high mortality rates; virus could become adapted to man. (Greenwood et al., 2002)

Virus classification

Influenza is an extremely variable, fast mutating virus. There are three main types, or genera Influenza A virus, B, and C though they are related each has different disease characteristic. Of the three type's virus, influenza A mutates the fastest, and as a result it is classified into a number of subtypes. Influenza B involves more slowly but still has many strains. Influenza C is the most stable of the three viruses.

influenza A

Influenza A virus causes the most severe form of influenza. It mutates 2-3 times faster than influenza B virus and is responsible for most large pandemics.

Influenza A virus classification is based on variation on two proteins found on the surface of the virus which is Hemaglutinine (H) has 16 subtypes and Neuraminidase (N) has 9 subtypes. The most significant subtypes to human are H1N1, H1N2, and H3N2 viruses.

Subtypes H1N1 is responsible for both the deadly 1918 Spanish flu pandemic and 2009 swine flu outbreak. H5N1 subtypes associated with pandemic avian flu.

Influenza A subtypes are further divided into strains that are named after the location and year of out breaks they cause. For instant, the virus strain that caused a swine flu out break among soldiers in new jersey in 1976 is called A new jersey 1976 (H1N1), the strain number may also be incorporate into the strain name.

2. Influenza B

Influenza B can cause death in humans, but is not known for causing worldwide pandemic. It can cause spark epidemics but these are generally less severe than those that can cause influenza A virus.

Influenza B virus does not go through the kind of revolution that changes in the surface protein of the virus as influenza A virus do. It mutates though more slowly than influenza A and has different strains.

3. Influenza C

Is the rarest and most stable of the three species of influenza, it usually mild illnesses though it can occasionally cause more sever flu Out breaks are typically local and do not become large epidemics or global pandemics for example California.


Virus structure

The influenza virus is roughly spherical and it is an enveloped virus, the outer layer is a lipid membrane which is taken from the host cell in which the virus multiplies. Instead into the lipid membrane are spikes, which are proteins for example, glycoprotein because they consist of protein linked to sugar known as Hemaglutinine and Neuraminidase, these are the proteins that determine the types of influenza virus A, B or C and the subtypes for example A(H1N1), these proteins are important in the immune response against the virus antibodies. (

Figure1 adopted from (

Embedded the lipid membrane is the M2 protein and beneath it is a viral protein called M1 or matrix protein. This protein gives strength and rigidity t the lipid envelope. Within the interior of the virion are the viral RNAs these are the genetic material of the virus. Each RNA segments as they are called consist of RNA joined with several proteins shown in the figure1 (B1, PB2, PA, NP). These RNA segments are the gene of influenza virus. The interior of the virion also contain a protein called NEP.

HA (hemagglutinin) protein: The HA protein is involved in attachment and membrane fusion in the endosome of the infected cell. The receptor binding site on the virus is in a pocket that is not exposed to the immune system. The antigenic domains are on the surface. These can be altered and the virus can thus avoid a humoral response without affecting its ability to bind to the receptor.

NA (neuraminidase) protein:The neuraminidase protein digests sialic acid (neuraminic acid) - which most cells have on their surface. Since sialic acid is part of the virus receptor, when the virus binds to the cell, it will be internalized (endocytosed). By late in infection, the sialic acid will have been removed from the infected cell surface by the neuraminidase making it is easier for the progeny virions to diffuse away once they exit the cell. Neuraminidase is also involved in penetration of the mucus layer in the respiratory tract.

Antigenic drift: Antigenic drift is due to mutation. Antibodies to the HA protein are the most important in protection, although those to NA also play a role. Both proteins undergo antigenic drift (i.e. accumulate mutations) and accumulate changes such that an individual immune to the original strain is not immune to the drifted one. Antigenic drift results in sporadic outbreaks and limited epidemics.

Antigenic shift: Antigenic shift is due to reassortment. In the case of influenza A, antigenic shift periodically occurs. Apparently "new" HA and/or NA are found in the circulating viral strains. There is little immunity (particularly if both proteins change, or if new HA is present) and an epidemic/pandemic is seen. (


Influenza virus may be transmitted in humans in three ways;

By direct contact with infected individuals.

By contact with contaminated objects for example door handles.

By inhalation of virus laden aerosols.

Influenza A virus is essentially an avian virus that has recently crossed into mammals; birds have the most number and rand of influenza strains.

Every 10-15 years a major new pandemic strain appears in man with a totally new HA and sometimes a new NA as well (antigenic shift).

Over the subsequent years this strain undergoes minor changes (antigenic drift) every two to three years, possibly by selective antibody pressure in the population of humans infected. . (Greenwood et al., 2002)


Influenza was responsible for the most devastating plague in human history. The Spanish flu that swept around the world killed around 675.000 people in the United Kingdom and an estimated 20-50 million people around the world.

Influenza A Evolution

1874 --- (H3N8)

1890 --- (H2N2) .........................Pandemic

1902 --- (H3N2)

1918 --- (H1N1)..........................Pandemic

1933 --- (H1N1)..........................First strains isolated

1947 --- (H1N1)..........................Variation detected

1957 --- (H2N2).........................."Asian" Flu pandemic

1968 --- (H3N2).........................."Hong Kong" Flu pandemic

1976 --- (H1N1).........................."Swine" Flu, non-epidemic

1977 --- (H1N1) + (H3N2)........."Russian" Flu epidemic (

In late March and early April 2009, an outbreak of H1N1 influenza A virus infection was detected in Mexico, with subsequent cases observed in many other countries.On June 11, 2009, the World Health Organization raised its pandemic alert level to the highest level.

On 29 January 2010 the WHO reported that more than 209 countries and overseas territories or communities have reported laboratory confirmed cases of pandemic influenza H1N1 2009, including at least 14711 deaths. (


The pathogenicity and virulence of the influenza virus is determined by several interacting factors:

Host factors:

Presence of target receptors on host cells

Availability of enzymes in host cells which are essential for viral entry and replication

State of immunocompetence of the individual host

Specific immunity against certain viral epitopes in the individual host and target population

Ability of the immune system to control the viral replication effectively without causing serious collateral damage for the host by its inflammatory response

Viral factors:

Ability to bind to host cells

Ability of virus shedding

Restriction of cytopathogenic effects to allow for an appropriate balance between viral replication and control by the host

Escape from immunosurveillance by evolution of antigenic variation driven by selective pressure of the immune response

Escape from immunosurveillance by recombination with different virus strains from zoonotic disease

Modulation of the immune response to attenuate effective host defense mechanisms

The main targets of the influenza virus are the columnar epithelial cells of the respiratory tract. In influenza infection, the receptor binding site of viral hemagglutinin (HA) is required for binding to galactose bound sialic acid on the surface of host cells. Certain areas of the binding site of HA are highly conserved between subtypes of the influenza virus. Hosts may prevent the attachment by several mechanisms:

(1) Specific immune response and secretion of specific IgA antibodies,

(2) Unspecific mechanisms, such as mucociliary clearance or production of mucoproteins that able to bind to viral hemagglutinin, and

(3) Genetic diversification of the host receptor (sialic acid), which is highly conserved in the same species, but differs between avian and human receptors.

Once influenza has efficiently infected respiratory epithelial cells, replication occurs within hours and numerous virions are produced. Infectious particles are preferentially released from the apical plasma membrane of epithelial cells into the airways by a process called budding. This favors the swift spread of the virus within the lungs due to the rapid infection of neighboring cells. (

Immune response:

Influenza causes an acute infection of the host and initiates a cascade of immune reactions activating almost all parts of the immune defense system. Most of the initial innate response, including cytokine release (IFNα/β), influx of neutrophil granulocytes or natural killer cells, and cell activation, is responsible for the acute onset of the clinical symptoms. Innate immunity is an essential prerequisite for the adaptive immune response, firstly, to limit the initial viral replication and antigen load, and secondly, because the antigen-specific lymphocytes of the adaptive immune response are activated by co-stimulatory molecules that are induced on cells of the innate immune system during their interaction with viruses (Figure). Influenza viruses, however, encode in the non-structural protein1 (NS1) mechanisms to evade and antagonize the IFN α/β response. NS1 is likely to sequester viral dsRNA which prevents recognition of this dangerous molecule by cellular sensors which would otherwise trigger IFN α/β release

The adaptive immune response requires some days to be effective but then helps to contain the viral spread, to eradicate the virus, and finally to establish a memory response resulting in a long-lived resistance to re-infection with homologous virus. Cross-protection within a subtype of influenza has only rarely been observed and infections essentially induce no protection across subtypes or between types A and B.

Influenza infection induces both systemic and local antibody (humoral immunity), as well as cytotoxic T cell responses (cellular immunity), each of which is important in recovery from acute infection and resistance to reinfection. (

Incubation period of the virus:

The incubation period of influenza lasts from 1 to 4 days, with 2 days being the average. Persons become infectious starting 1 day before their symptoms being and remain infectious through approximately 5 days after illness onset. Children can be infectious for grater than 10 days, and young children can shed virus for up to 6 days before their illness onset. Severely immunocompromised persons can shed virus for weeks or months.

Symptoms of influenza

When a person is infected with influenza the following symptoms will appear:

Fever which rise up to 38 and children up to 40.

Headache, achy muscle and joints pain

Tired and weakness

Chills and sweating

Nasal congestion

Sore throat and dry cough

Loss of appetite

Diarrhea and vomiting (these symptoms may affect children more than adults).


Laboratory diagnosis

Virus Isolation - Throat swabs, NPA and nasal washings may be used for virus isolation. It is reported that nasal washings are the best specimens for virus isolation. The specimen may be inoculated in embryonated eggs or tissue culture. 10-12 day embryonated eggs are used for virus isolation. The specimen is inoculated into the amniotic cavity. The virus replicates in the cells of the amniotic membrane and large quantities are released back into the amniotic fluid. After 2-3 days incubation, virus in the amniotic fluid can be detected by adding aliquots of harvested amniotic fluid to chick, guinea pig, or human erythrocytes.

Rapid Diagnosis by Immunofluorescence - cells from pathological specimens may be examined for the presence of influenza A and B antigens by indirect immunofluorescence. , but EIA tests for the detection of influenza A viral antigens are easier to interpret than immunofluorescence. PCR assays for the detection of influenza RNA can also be used.

Serology - this is done by the demonstration of a rise in serum antibody to the infecting virus. Complement fixative test is the most common method used using the type specific soluble antigen. (


Pneumonia is the major serious complication of influenza. It can develop about five days after viral influenza and nearly always occurs in susceptible individuals about five days after onset. This can be viral pneumonia, in which the influenza virus itself spreads into the lungs, or bacterial pneumonia, in which unrelated bacteria (such as pneumococci). In both cases, the person may have a worsened cough, difficulty breathing, persistent or recurring fever, and sometimes bloody sputum. Pneumonia is more common in older people and in people with heart or lung disease.

Children under 1 year old have a very high risk, not only for pneumonia but also for other complications, including meningitis and encephalitis (inflammations in central nervous system). The risk declines after age one but is still elevated in children aged three to five. (Greenwood et al., 2002).


Amantadine and rimantadine are chemically related antiviral drugs active against influenza A viruses. After influenza A viruses enter cells, these drugs inhibit the uncoating of influenza A viruses by blocking the ion-channel activity of the viral M2 protein. Amantadine was approved in 1976 for treatment and prophylaxis of influenza type A infection in adults and children aged greater than or equal to 1 year. Rimantadine was approved in 1993 for treatment and prophylaxis of influenza type A infection in adults. For children, rimantadine was approved only for prophylaxis; however, many experts consider rimantadine appropriate for treatment of influenza A in children.

More recently two neuraminidase inhibitors, zanamivir and oseltamivir they can reduce the duration of symptoms by 1-3 days if given within 36 hours of illness onset. zanamivir is administrated by inhalation of a dry powder twice daily for five days.

Oseltamivir is given by mouth twice daily dosage for five to seven days, these has been used in those with normal renal function, but it should be used once a day when renal function is impaired. (

Prevention and control

Influenza vaccine increases a person's defenses against the influenza virus. It works by introducing very small amounts of viral components into the body. These components are enough to stimulate the production of antibodies (cells designed to attack that particular virus), which will remain in the body and ready to attack that same influenza virus in the future.

Reasonably effective ways to reduce the transmission of influenza include good personal health and hygiene habits such as: not touching your eyes, nose or mouth frequent hand washing (with soap and water or with alcohol-based hand rubs) covering coughs and sneezes; avoiding close contact with sick people; and staying home yourself if you are sick. Avoiding spitting is also recommended

Although face masks might help prevent transmission when caring for patients. Since influenza spreads through both aerosols and contact with contaminated surfaces, surface sanitizing may help prevent some infections. Alcohol is an effective sanitizer against influenza viruses. (


Future outlook