Influenza - What is Influenza?

Influenza, commonly referred to as the flu, is an infectious disease caused by RNA viruses of the family Orthomyxoviridae (the influenza viruses), that affects birds and mammals.

The most common symptoms of the disease are chills, fever, sore throat, muscle pains, severe headache, coughing, weakness/fatigue and general discomfort. Sore throat, fever and coughs are the most frequent symptoms.

In more serious cases, influenza causes pneumonia, which can be fatal, particularly for the young and the elderly. Although it is often confused with other influenza-like illnesses, especially the common cold, influenza is a more severe disease than the common cold and is caused by a different type of virus.

Influenza may produce nausea and vomiting, particularly in children,

Typically, influenza is transmitted through the air by coughs or sneezes, creating aerosols containing the virus. Influenza can also be transmitted by direct contact with bird droppings or nasal secretions, or through contact with contaminated surfaces.

Airborne aerosols have been thought to cause most infections, although which means of transmission is most important is not absolutely clear. As the virus can be inactivated by soap, frequent hand washing reduces the risk of infection.

Influenza spreads around the world in seasonal epidemics, resulting in the deaths of between and people every year, up to millions in some pandemic years.

On average 41,400 people died each year in the United States between 1979 and 2001 from influenza.

Three influenza pandemics occurred in the 20th century and killed tens of millions of people, with each of these pandemics being caused by the appearance of a new strain of the virus in humans.

Often, these new strains appear when an existing flu virus spreads to humans from other animal species, or when an existing human strain picks up new genes from a virus that usually infects birds or pigs.

An avian strain named H5N1 raised the concern of a new influenza pandemic, after it emerged in Asia in the 1990s, but it has not evolved to a form that spreads easily between people.

In April 2009 a novel flu strain evolved that combined genes from human, pig, and bird flu, initially dubbed "swine flu" and also known as influenza A/H1N1, emerged in Mexico, the United States, and several other nations.

The World Health Organization officially declared the outbreak to be a pandemic on June 11, 2009. The WHO's declaration of a pandemic level 6 was an indication of spread, not severity, the strain actually having a lower mortality rate than common flu outbreaks.

Vaccinations against influenza are usually given to people in developed countries and to farmed poultry.

The most common human vaccine is the trivalent influenza vaccine (TIV) that contains purified and inactivated material from three viral strains. Typically, this vaccine includes material from two influenza A virus subtypes and one influenza B virus strain.

The TIV carries no risk of transmitting the disease, and it has very low reactivity. A vaccine formulated for one year may be ineffective in the following year, since the influenza virus evolves rapidly, and new strains quickly replace the older ones.

Antiviral drugs can be used to treat influenza, with neuraminidase inhibitors being particularly effective.

The word ''Influenza'' comes from the Italian language meaning "influence" and refers to the cause of the disease; initially, this ascribed illness to unfavorable astrological influences.

Changes in medical thought led to its modification to ''influenza del freddo'', meaning "influence of the cold".

The word ''influenza'' was first used in English in 1743 when it was adopted, with an anglicized pronunciation, during an outbreak of the disease in Europe.

Archaic terms for influenza include ''epidemic catarrh'', ''grippe'' (from the French), ''sweating sickness'', and ''Spanish fever'' (particularly for the 1918 flu pandemic strain).

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Types of Influenza

Types of influenza virus

In virus classification influenza viruses are RNA viruses that make up three of the five genera of the family Orthomyxoviridae:

  • Influenzavirus A
  • Influenzavirus B
  • Influenzavirus C

These viruses are only distantly related to the human parainfluenza viruses, which are RNA viruses belonging to the paramyxovirus family that are a common cause of respiratory infections in children such as croup, but can also cause a disease similar to influenza in adults.

Influenzavirus A

This genus has one species, influenza A virus. Wild aquatic birds are the natural hosts for a large variety of influenza A. Occasionally, viruses are transmitted to other species and may then cause devastating outbreaks in domestic poultry or give rise to human influenza pandemics.

The type A viruses are the most virulent human pathogens among the three influenza types and cause the most severe disease. The influenza A virus can be subdivided into different serotypes based on the antibody response to these viruses.

  • H1N2, endemic in humans and pigs
  • H9N2
  • H7N2
  • H7N3
  • H10N7
Influenzavirus B

This genus has one species, influenza B virus. Influenza B almost exclusively infects humans and is less common than influenza A.

The only other animals known to be susceptible to influenza B infection are the seal and the ferret.

This type of influenza mutates at a rate 2–3 times slower than type A and consequently is less genetically diverse, with only one influenza B serotype.

This reduced rate of antigenic change, combined with its limited host range (inhibiting cross species antigenic shift), ensures that pandemics of influenza B do not occur.

Influenzavirus C

This genus has one species, influenza C virus, which infects humans, dogs and pigs, sometimes causing both severe illness and local epidemics.

Structure, properties, and subtype nomenclature

Influenzaviruses A, B and C are very similar in overall structure. The virus particle is 80–120 nanometres in diameter and usually roughly spherical, although filamentous forms can occur. These filamentous forms are more common in influenza C, which can form cordlike structures up to 500 micrometres long on the surfaces of infected cells.

Hemagglutinin (HA) and neuraminidase (NA) are the two large glycoproteins on the outside of the viral particles.

HA is a lectin that mediates binding of the virus to target cells and entry of the viral genome into the target cell, while NA is involved in the release of progeny virus from infected cells, by cleaving sugars that bind the mature viral particles. Thus, these proteins are targets for antiviral drugs.

Furthermore, they are antigens to which antibodies can be raised. Influenza A viruses are classified into subtypes based on antibody responses to HA and NA. These different types of HA and NA form the basis of the ''H'' and ''N'' distinctions in, for example, ''H5N1''.


Viruses can only replicate in living cells. Influenza infection and replication is a multi-step process: firstly the virus has to bind to and enter the cell, then deliver its genome to a site where it can produce new copies of viral proteins and RNA, assemble these components into new viral particles and finally exit the host cell.

Influenza viruses bind through hemagglutinin onto sialic acid sugars on the surfaces of epithelial cells; typically in the nose, throat and lungs of mammals and intestines of birds. After the hemagglutinin is cleaved by a protease, the cell imports the virus by endocytosis.

Once inside the cell, the acidic conditions in the endosome cause two events to happen: first part of the hemagglutinin protein fuses the viral envelope with the vacuole's membrane, then the M2 ion channel allows protons to move through the viral envelope and acidify the core of the virus, which causes the core to dissemble and release the viral RNA and core proteins. The M2 ion channel is blocked by amantadine drugs, preventing infection.

These core proteins and vRNA form a complex that is transported into the cell nucleus, where the RNA-dependent RNA polymerase begins transcribing complementary positive-sense vRNA.

The vRNA is either exported into the cytoplasm and translated, or remains in the nucleus.

Newly synthesised viral proteins are either secreted through the Golgi apparatus onto the cell surface (in the case of neuraminidase and hemagglutinin) or transported back into the nucleus to bind vRNA and form new viral genome particles.

Other viral proteins have multiple actions in the host cell, including degrading cellular mRNA and using the released nucleotides for vRNA synthesis and also inhibiting translation of host-cell mRNAs.

Negative-sense vRNAs that form the genomes of future viruses, RNA-dependent RNA polymerase, and other viral proteins are assembled into a virion.

Hemagglutinin and neuraminidase molecules cluster into a bulge in the cell membrane. The vRNA and viral core proteins leave the nucleus and enter this membrane protrusion.

The mature virus buds off from the cell in a sphere of host phospholipid membrane, acquiring hemagglutinin and neuraminidase with this membrane coat.

As before, the viruses adhere to the cell through hemagglutinin; the mature viruses detach once their neuraminidase has cleaved sialic acid residues from the host cell.

The separation of the genome into eight separate segments of vRNA allows mixing or reassortment of vRNAs if more than one type of influenza virus infects a single cell. The resulting rapid change in viral genetics produces antigenic shifts, which are sudden changes from one antigen to another.

These sudden large changes allow the virus to infect new host species and quickly overcome protective immunity. Many people are so ill that they are confined to bed for several days, with aches and pains throughout their bodies, which are worse in their backs and legs. (may be severe in children with influenza B).

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Influenza Epidemiology

Seasonal variations

Influenza reaches peak prevalence in winter, and because the Northern and Southern Hemispheres have winter at different times of the year, there are actually two different flu seasons each year.

This is why the World Health Organization (assisted by the National Influenza Centers) makes recommendations for two different vaccine formulations every year; one for the Northern, and one for the Southern Hemisphere.

A long-standing puzzle has been why outbreaks of the flu occur seasonally rather than uniformly throughout the year.

One possible explanation is that, because people are indoors more often during the winter, they are in close contact more often, and this promotes transmission from person to person.

Increased travel due to the Northern Hemisphere winter holiday season may also play a role.

Another factor is that cold temperatures lead to drier air, which may dehydrate mucus, preventing the body from effectively expelling virus particles.

The virus also survives longer on surfaces at colder temperatures and aerosol transmission of the virus is highest in cold environments (less than 5 °C) with low relative humidity. Indeed, the lower air humidity in winter seems to be the main cause of seasonal influenza transmission in temperate regions.

However, seasonal changes in infection rates also occur in tropical regions, and in some countries these peaks of infection are seen mainly during the rainy season.

Seasonal changes in contact rates from school terms, which are a major factor in other childhood diseases such as measles and pertussis, may also play a role in the flu.

A combination of these small seasonal effects may be amplified by dynamical resonance with the endogenous disease cycles. H5N1 exhibits seasonality in both humans and birds.

An alternative hypothesis to explain seasonality in influenza infections is an effect of vitamin D levels on immunity to the virus. This idea was first proposed by Robert Edgar Hope-Simpson in 1965. He proposed that the cause of influenza epidemics during winter may be connected to seasonal fluctuations of vitamin D, which is produced in the skin under the influence of solar (or artificial) UV radiation.

This could explain why influenza occurs mostly in winter and during the tropical rainy season, when people stay indoors, away from the sun, and their vitamin D levels fall.

Epidemic and pandemic spread

As influenza is caused by a variety of species and strains of viruses, in any given year some strains can die out while others create epidemics, while yet another strain can cause a pandemic.

Typically, in a year's normal two flu seasons (one per hemisphere), there are between three and five million cases of severe illness and up to 500,000 deaths worldwide, which by some definitions is a yearly influenza epidemic.

Although the incidence of influenza can vary widely between years, approximately 36,000 deaths and more than 200,000 hospitalizations are directly associated with influenza every year in the United States.

Roughly three times per century, a pandemic occurs, which infects a large proportion of the world's population and can kill tens of millions of people.

Indeed, one study estimated that if a strain with similar virulence to the 1918 influenza emerged today, it could kill between 50 and 80 million people.

New influenza viruses are constantly evolving by mutation or by reassortment. However, since the strains produced by drift will still be reasonably similar to the older strains, some people will still be immune to them.

In contrast, when influenza viruses reassort, they acquire completely new antigens—for example by reassortment between avian strains and human strains; this is called antigenic shift.

If a human influenza virus is produced that has entirely new antigens, everybody will be susceptible, and the novel influenza will spread uncontrollably, causing a pandemic.

In contrast to this model of pandemics based on antigenic drift and shift, an alternative approach has been proposed where the periodic pandemics are produced by interactions of a fixed set of viral strains with a human population with a constantly changing set of immunities to different viral strains.

This article is licensed under the Creative Commons Attribution-ShareAlike License. It uses material from the Wikipedia article on "Influenza" All material adapted used from Wikipedia is available under the terms of the Creative Commons Attribution-ShareAlike License. Wikipedia® itself is a registered trademark of the Wikimedia Foundation, Inc.