Influenzavirus – Classifications Of Influenza Virus
The various number of virus classification or influenza viruses are the RNA viruses which makes up the three out of the five genera family Orthomyxoviridae (Cole and Cook, 2008): Influenzavirus A, Influenza-virus B, Influenzavirus C
These viruses are only distantly related to the human para-influenza 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 (Winther et al., 2008).
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 (Smith et al., 2008). 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 (Mitamura and Sugaya, 2006). The serotypes that have been confirmed in humans, ordered by the number of known human pandemic deaths, are:
- H1N1, which caused Spanish Flu in 1918, and Swine Flu in 2009
- H2N2, which caused Asian Flu in 1957
- H3N2, which caused Hong Kong Flu in 1968
- H5N1, which caused Bird Flu in 2004
- H7N7, which has unusual zoonotic potential (Beck et al., 2013)
- H1N2, endemic in humans, pigs and birds
This genus has one species, influenza B virus. Influenza B almost exclusively infects humans (Holmes et al., 2005) and is less common than influenza A. There are other animals that is known with its susceptible to influenza B infections, and that animal has the seal and the ferret also. This type of influenza has the ability to mutates at at least the rate of 2–3 times slower than type A (Kobasaet al., 2007) and consequently with a lesser genetically diverse gene, with one influenza B serotype (Holmes et al., 2005). The outcome of this lack of antigenic diversity can lead to a certain level of immunity to the influenza B which is usually acquired from the early age. Meanwhile, the influenza B can actually mutate enough to be a lasting immunity which is supposed not to be possible. 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 (Beigel and Bray, 2008).
This genus has one species, influenza C virus, which infects humans, dogs and pigs, sometimes causing both severe illness and local epidemics (Liu et al., 2011; Ghedin et al., 2005). However, reports has it that influenza C is less common when in comparison with the other types which are assumed to usually be the only one that causes mild disease in children (Suzuki, 2005; Matsuzakiet al., 2006).
Structure, Properties, And Subtype Nomenclature
Influenza-viruses A, B and C are very similar in overall structure (Katagiriet al., 2003). The avian influenza virus particle which is measured at a 80–120 nanometers mainly in diameter are most often roughly spherical, perhaps, in some situation filamentous forms can still occur (Taubenberger and Morens, 2008). These filamentous forms are more common in influenza C, which can form cordlike structures up to 500 micrometers long on the surfaces of infected cells (Klenket al., 2008).
However, despite these varied shapes, the viral particles of all Influenzavirus are similar in composition (Klenket al., 2008). They are mostly made of a viral enveloping that mainly contains two types of glycol-proteins, that is wrapped around a central core. Central core contains viral RNA and also other unknown viral proteins that packages as well as protect the RNA.
The RNA sometimes tends to be in a single stranded but in special cases it can be doubled. In influenza virus, genome is not in single pieces of nucleic acid; rather, it has in it about seven to eight pieces of a segmented negative sense in the RNA, each piece of RNA containing either one or two genes, which code for a gene product (protein) (Klenket al., 2008).
Take an example, influenza A genome has in it the 11 genes on an eight pieces of RNA, encoding for 11 proteins: hemag-glutinin (HA) as well as the neuraminidase (NA) or even the nucleoprotein (NP), M1, M2, NS1, NS2(NEP: nuclear export protein), PA, PB1 (polymerase basic 1), PB1-F2 and PB2 (Ebell et al., 2013).
Hemag-glutinin (HA) and neuraminidase (NA) are the two large glycol-proteins on the outside of the viral particles. Ha as a lectin which mediates as the binding of the virus to a target cells and also an entry of the viral genome into a target cell, while the NA is involved in the release of progeny virus from infected cells, by cleaving sugars that bind the mature viral particles (Jefferson et al., 2011).
Thus, these proteins are targets for antiviral drugs (Michiels et al., 2013). Furthermore, they are antigens to which antibodies can be raised. Influenza A viruses which is classified according to a subtypes that are based on antibody responses either HA or NA. These different types of HA and NA form the basis of the H and N distinctions in, for example, H5N1 (Ebell et al., 2013). There are 16 H and 9 N subtypes known, but only H 1, 2 and 3, and N 1 and 2 are commonly found in humans (Palmer, 2011).
Viruses can replicate only in living cells (Monto et al., 2000). Influenza infection or other replica is in a multi-step process: First of all, the influenza virus has to bind and then enter the cell itself, 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, last, exit the host cell (Kobasaet al., 2007).
It is well documented that Influenzavirus can bind through a hemagglutinin into a sialic acid sugars which is often on the surfaces of an epithelial cells function, typically in the nose, throat, and lungs of mammals, and intestines of birds (Stage 1 in infection figure) (Brankston et al., 2007). After the hemagglutinin is cleaved by a protease, the cell imports the virus by endocytosis (Suzuki et al., 2007).
The intracellular details are still being elucidated. It is an established fact that the virions converge that links to the microtubule organizing center can as well interact with the acidic-endosomes and which may then enter it’s targeted endosomes for the genome release (Longo, 2012).
Once a cell and the acidic conditions that are in the endosome which has the capacity to cause two events to happen: First part which is the hemagglutinin protein fuses that has the viral envelope the vacuole’s membrane of the hemagglutinin protein, that where M2 ion can then be channel or it now allows protons to freely move through what we call the viral envelope and also acidify all the core of the virus, which can make the core to dissemble or may even make it to release the viral RNA and core proteins (Klenket al., 2008).
The viral RNA (vRNA) molecules, accessory proteins and RNA-dependent RNA polymerase are then released into the cytoplasm (Stage 2).The M2 ion channel is blocked by amantadine drugs, preventing infection (Michiels et al., 2013).
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 (Steps 3a and b) (Duben et al., 2013). The vRNAeither is exported into the cytoplasm and translated (step 4) or remains in the nucleus.
Now the newly syn-thesized viral proteins can be secreted using Golgi apparatus onto cell surface (for example neuraminidase and hemagglutinin, step 5b) it can as well be moved backwards to a nucleus which will then bind the vRNA or even form a new viral genome particles (step 5a).
Also the other viral proteins can as well possess a multiple actions through the host cell, this also includes degrading of the cellular mRNA by using a released nucleotides meant for the vRNA synthesis and also inhibiting translation of host-cell mRNAs (Brankston et al., 2007).
There are negative-sense in the vRNAs that forms a genomes of future viruses, RNA-dependent RNA polymerase, and other viral proteins are assembled into a virion. The Hema-gglutinin as well as the neuraminidase molecules muster to a bulge seen the cell membrane. In most cases vRNA which has a viral core proteins most times leave the nucleus and enter this membrane protrusion (step 6).
Mature Influenzavirus may buds off mostly from the cell center into a sphere of it’s host of phospholipid membrane, then acquiring the hema-gglutinin and also the neuraminidase coupled with the membrane coat (step 7) (Dubenet al., 2011).
As was reviewed previously, these viruses adhere to cell through the hema-gglutinin; these mature viruses detach only once from their neuraminidase which has a cleaved sialic acid residues from the host cell. After the release of new influenzaviruse, the host cell dies (Call et al., 2005).
Because of the absence of RNA proofreading enzymes, the RNA-dependent RNA polymerase that copies the viral genome makes an error roughly every 10 thousand nucleotides, which is the approximate length of the influenza vRNA.
However, majority of those newly manufactured or made up Influenzavirus are known as mutants; that causes what we call antigenic drift, these are slow to change in the antigens or on the viral surface over time (Suzuki et al., 2007). A separation in the genome into eight separate segments of vRNA gives way to allowing the mixing or re-assortment of vRNAs if more than one type of influenza virus infects a single cell.
This can result into a rapid change on the viral genetics produces in a antigenic shifts, and then a sudden change from an antigen to another antigen. These holistic changes now makes the virus to infect any new host species and then they quickly overcome its protective immunity. This is important in the emergence of pandemics, as discussed below in the section on Epidemiology (Dubenet al., 2011).