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A virus is "a piece of nucleic acid surrounded by bad news" stated by a Nobel Prize awarded biologist, Peter Medawar. With the stated nature of viruses, there is definitely an indicative nature of the appearance of negativity that in return creates threat in the survival issues of humans. The major component of DNA and RNA makes the virus a more complex component that continually challenges the medical field.
Perhaps, one of the most common and known form of a virus is the influenza .Influenza is also known as seasonal influenza, caused by an influenza virus and is basically identified in the form of common colds.
Types of Influenza
There are basically three types of influenza virus that may infect humans, namely: type A, B and C [4, 7-9,12]. Type A is further elaborated as following:
These types are known to cause major pandemic and are usually classified according to its protein subtypes and different combinations. It was first isolated in 1933 by intranasal inoculation of ferret [5,6,12].Although they are stressed as a common influenza form, these types are said to be the scariest among the three, with the fact that it has historically caused a massive and most serious cases. It is said that it can contaminate most on people and animals like birds, pigs, horses or whales, yet its natural host are the wild birds.
Structure of influenza A virus:
Influenza A is classified to the genus Orthomyxovirus in the family of Orthomyxoviridae. It is single stranded RNA with negative polarity [5,6,11,14,15,20,26,27,31]. The cell membrane is spherical or elongated made of lipid layer, in which the virus stole it from other cells it attached to and used to replicate inside it. These make up the virus envelope that measure from 80-120 nm in diameter[5,6,11,14,15,26,27,31]. To form this helical structure the RNA is associated with nucleoprotein (NP). NP is specific antigen found in all influenza strains. [5,6,11,14,15,26,27,31]
The genome is segmented with eight single stranded RNA. The nucleocapsid is surrounded by a matrix protein (M protein), which makes up 35 - 45 % of the particle mass. In the cell wall there are two types of glycoproteins spikes projection, haemagglutinin (HA) which is about 80% and the other 20% is neuraminidase (NA) [5,6,20,26,27,31].
Haemagglutinin is named so because; it agglutinates certain species of erythrocytes. It consist of two polypeptide chains HA1 and HA2 . These two chains help the virus to attach to the cellular receptor. There are 16 types of HA[12.20].
Neuraminidase is important in the cleavage of sialic acid this allows the virus to permeate mucin and escape from inhibitors. It is also important in the final stage to release new particles of the virus. There are 9 types of NA[12,20].
The virus can be inactivated by exposure to heat of 56 Í¦C for 30 minutes or by using variety of substances such as 20% ether, phenol and salt of heavy materials.
Table 1 bellow shows the eight genomic ssRNA segments and its fuction.adapted from .
According to WHO ( World Health Organiser ) system of Nomenclature includes host of origin, geographical origin, strain number and the year of isolation.
FIigure 2: Type A influenza Nomenclature .Adapted from 
Classification of influenza A virus:
Type A influenza are subtypes according to the surface antigen heamagglutinin (H) and neuraminidase (N) as it is shown in table 2 [5,14]:
It takes up to 6 hours[5,20].In order to enable the virus to inter the host cell it have to bind by its haemagglutinin to the sialic acid which found on the glycoproteins receptors of the host epithelial cells of the respiratory tract[5,6,10,16-18]. By the action of proteases haemagglutinin is cleaved, and the cell endocytosis the virus. At low PH environment inside the endosome the virus changes its shape and releases its envelope with the endosomal membrane. The vrial RNA (vRNA) and RNA-dependent RNA polymerase are then released into the cytoplasm[5,20,27]. Inside the host nucleus RNA-dependent RNA polymerase are transcribing complementary positive-sense vRNA. The virus is then translated from transcribed m-RNA. Negative sense RNA produced, that form the future virus. These new virus is encased in its protein capside with the new matrix materials. Then, it moves to surface where the Neuraminidase and haemagglutinin have been moved into the cell membrane[5,6,10,16-18,20,27]. Finally, the progeny is released by budding as its showing in figure 2 
Air is the main vessel in the widespread of Influenza A viruses. The viruses are transmitted through direct contact with droplets (by sneezing and coughing) that can easily penetrate through the nose or mouth[5,14]. Aside from this, persons who have contacted surfaces or basic things like knobs or telephones, can also be elicited to possible victims especially if they have handled such from the hands passed to the mouth or nose.
On the other hand, other influenza A viruses can be transmitted with the aid of the animals. As original settlers of viruses, the birds or ducks can transmit the virus through other animals as well like the pigs, which more likely to bring it to humans (1).
Pathogenesis and immune response:
Influenza A pathogenesis is depending in many factors, that may involves host, viral and environmental factors . Each of the eight genes of the ssRNA has a specific function that plays a role in the virus pathogenesis. Influenza A virus shows tropism for respiratory tract because; the virus needs alpha2-3 linker receptor and trypsin-like protease. This found only in the respiratory tract.
Highly pathogenic H5 and H7 cause rapidly fatal disease due to the presence of HA protein that characterised by mutable residues at the cleavage site. This protein cleaves by furin and other proteases . That makes the infection with H7N7 and H5N1 fatal . The type of neuraminidase(NA) also determine the pathogenesis. NA binds to plasminogen and that leads to concentrated the ubiquitous protease and increase the cleavage of HA. Non-structural protein(NS1) plays a role to unable the infected cell to grow and also inhibits interferon response in the cell[5,20]."Interestingly, studies with the genetically reconstructed 1918 Spanish influenza pandemic virus (H1N1) revealed additional mechanisms of NA-mediated HA cleavability that may be relevant to the replication and virulence of that virus".
Once the virus infect the host, it initiate immune response involves rapid innate response and a slower adaptive immune response including Cellular and Humeral mediated cell response[5,21,22]. Once the innate response activated(dendritic cell activates T cell by presenting the MHC antigen on its surface), chemokines and cytokines are produced. These chemicals are produced by the infested cells and some lymphocytes . Example of these cytokines are type 1 interferons(IFNs), (IFNÎ±/Î²) these cytokines bind to the receptors of the infected cells to induce antiviral response . However, influenza virus encode in the non-structural protein 1 (NS1) which, play a role to prevent the recognition of the virus by cellular sensor that would trigger IFNÎ±/Î² release .
After few days the adaptive immune response activated to kill the virus and establish a memory to prevent re-infection with same virus[20,25]. The immune response to the infection induced both Cellular immunity by cytotoxic T lymphocytes and Humeral response example IgG and IgA antibodies.
However , the virus has the ability to trick our immune system by mutating its RNA sequence.
Influenza Virus Changes: Drift and Shift
There are two ways that determine the change in influenza viruses: antigenic drift and antigenic shift. Antigenic drift takes place via minor changes but its occurrence continue over time that might even produce new virus strains, unrecognizable by human antibodies [5,8,11,14,15,32]. One example is the flu virus that continually occurs in different periods of time, as it may have developed new strains of viruses that presently are not recognized by the bodies' antigens. It is also due to mutation with less number of epidemics or sporadic outbreaks [5,8,11,14,15,32].
Meanwhile, the antigenic shift is the sudden and major transition of viruses that results to a combination of either both the hemagglutinin and neuraminidase proteins and the hemagglutinin protein[5,8,11,14,15,32].These new protein combinations were not apparent in the human conditions for many years. Thus, the occurrence of new influenza A virus is the outcome of this antigenic shift. This will then possibly result to a pandemic threat, since human bodies does not yet have the capacity to produce antigens against the new type of virus [5,8,11,14,15,32].
Every year the outbreak of influenza A occurs in distinct variation. The NA and HA nature gives it the ability to change continually in antigenic characteristics. The table below shows history of influenza A since 1918 until 2007 and estimated number of infected people and the number of deaths.
The H1N1 type of influenza has currently feared most nations and it led to more than 18000 deaths in 2009/2010 . Aside from this, H1N2 and H3N2 are also circulating among the different parts in the world. There were significant changes in amino acid sequence of both HA and NA proteins. The point mutation which occurs in the amino acid sequence of H1N1 2009 is about 18% different from influenza H1N1 1918, 27.2% different from human H1N1 which isolated in 2008 and about 12% different from the 1976 swine flu.
Different types of respiratory specimens can be used to diagnosis influenza virus. The timing for collecting the sample is also very important. The test and the appropriate specimen also the time needed for the result shown in table 4 bellow[5,14,20,31]:
The virus has an incubation period of 18 to 72 hours[5,6].The onset of fever, colds and running nose apparently directs to the symptoms of common flu. Aside from these symptoms, the onset of headaches, massive malaise, joint and muscle pains and sore throat, also indicates seasonal influenza (5-7,20). Other signs also include shaking chills, chest pain or coughing that produces thick and yellowish-green-colored mucus (5-7,9). However, influenza can also cause severe damage among high risk individuals like the children and the old such as convulsions or ear infections and even death if not treated.
Table5 illustrated the complication of influenza A disease [5,6,10,11,20]
Since influenza A virus is transmitted via aerosol droplets, good hygiene may help in preventing the disease. There some outline advises to prevent influenza A. first, frequent hand washing with soap and water, particularly after coughing or sneezing and avoid touching the eyes and nose. Second, avoid contact with infected people. Third, don't share cutlery or drinks and eat balanced diet to keep in good health. Finally, surfaces commonly used must be disinfected[5,6,11,14].
The most effective way to prevent influenza A is by vaccination. Vaccine can be divided into two types killed virus vaccines (flu shot) and lived virus vaccines [5,20,40]. Whole virus vaccines, split or subunit and virosome are types of the killed vaccines. Whole virus vaccines gives a good immunogenicity and up to 60-90 % efficiency in both adult and children. Split or subunit virus vaccine is disturbed by detergents. It gives more immunogenic and it is safe to be given to children. Virosome are inactive vaccine. It use HA and NA as virus like particles which plays a role as adjuvant. Cold- Adapted Live attenuated influenza virus( LAIV) is also called nasal shot. It was licensed in 2003 in USA by FDA[20,40] (food and drug administration). The virus is able to replicate and induce immune response. It gives raised to IgA production .
The available antiviral drugs are first, Amantadine(Symmetrel®)and Rimantadine (Flumadine®) the role of these drugs is to block the M2 ion channel thus prevent the PH changes, so the nucleocapsid will not be released. In 2008/2009 all strains of H3N2 developed resistance[5,6,20,39].Second, Oseltamivir (Tamiflu®)and zanamivir (Relenza®), these drugs works buy blocking th NA protein that will prevent that virus frome reasing and separating the new virons. Oseltamivir can be giving orally but zanamivir mut be giving by inhalation[5,6,39].Finally, Ribavirin it acts on the RNA polymerase that inhabits the virus replication.Antiviral drugs should be giving within 48 hours of symptoms.Diagram6 bellow shows the therapeutics target of these drugs in the life cycle of the virus. Adapted from
Viruses are considered to be multifaceted and compound structures that continue to threaten the ordinary lives. The different historical accounts and stories behind the huge efforts made by the scientists prove man's unravelling conquest to further understand the phenomena and mysteries of human nature. There are some points are expected to be improved in the future in the case of vaccine .studies with promising result suggest that we can use DNA vaccination that's mean the administration of one or more influenza virus protein to encoded plasmid DNA. Another aspect is a new adjuvant approaches this contains cholesterol and viral particles that enhances the immunogenicity of the vaccine. This vaccine has been proven only in animal's model but not yet in human.