Molecular Biology of the Flu

There are two types of change: shift and drift. What are they? How do they differ?

Katelyn O'Rourke writes: A shift change is one in which can change quite rapidly, while a drift changes gradually over a specified allotment of time. The shift change is the difference between the shifts that are calculated for a predicted peak pair, as well as the adjacent observed-predicted peak pair. Various shifts can occur due to different atmospheric and gradual changes in our environment.

Gregory Zimmer writes: Influenza viruses can change in two different ways. They can Drift and Shift, or more accurately they are called Antigenic Drift and Antigenic Shift. Antigenic Drifts are small changes in the virus that happen continually over time. This produces new virus strains that may not be recognized by the body's immune system. The other type, Antigenic Shift is an abrupt, major change in the influenza A viruses, resulting in new hemagglutinin and/or new hemagglutinin and neuraminidase proteins in influenza viruses that infect humans. An antigenic shift results in a new influenza A subtype. When a shift happens, most people have little or no protection against the new virus.

Why does shift occur in flu?

Gregory Zimmer writes: The influenza virus causes the classic flu. Health care providers classify the virus as influenza type A and type B, each of which includes several offshoots called subtypes or strains. These strains are different from the original virus but retain some of its characteristics. I think that shifts and drifts occur because we as humans try to protect ourselves as much as we can. To do that we create a vaccine or a shot that can protect us against a certain strain or type of flu every year. Every year there is a new strain of subtype of the flu. This occurs because influenza has no other option to mutate or change because we found a new way to protect ourselves. This goes for much of any disease or organism, either change to adapt to a new environment or become extinct.

What is the property in its genome that allows this to occur?

Gregory Zimmer writes: Virions have a complex construction and consist of an envelope, a matrix protein, a nucleoprotein complex, a nucleocapsid, and a polymerase complex. Virions are enveloped. Virions are spherical to pleomorphic; filamentous forms occur and 80-120 nm in diameter; 200-300(-3000) nm long. The surface projections are distinctive about 500 spikes . The surface projections are composed of one type of protein, or different types of proteins. The surface projections are evenly covering the surface. They are densely dispersed (i.e. hemagglutinin-esterase (HEF)), or spaced widely apart (i.e. hemagglutinin (HA) the major glycoprotein is interposed irregularly by clusters of neuraminidase (NA), ratio of HA to NA about 4-5 to 1); evenly dispersed, or clustered. The surface projections comprise hemagglutinin, or neuraminidase, or esterase-esterase. Surface projections are 10-14 nm long; 4-6 nm in diameter. Capsid/nucleocapsid is elongated and exhibits helical symmetry. The nucleocapsid is helical. The nucleocapsid is segmented . And segments have different size classes. Has clear predominate lengths; of 50-130 nm (in different size classes); 9-15 nm in diameter. Nucleocapsids are segmented with loops at one end. To summarize or get to the point, the HA and NA property in the genome of the Influenza Virus allows this to occur. An example is H5N1, which is an Influenza A virus subtype. H5N1 is also known as the Avian Flu. If a mutation, or in this case a shift, occurs, it might remain an H5N1 subtype or could shift subtypes as did H2N2 when it evolved into the Hong Kong Flu strain of H3N2.

Why should we worry about all strains of flu? (Recombination/reassortment)

Lindsay Berman writes: The genetic material (RNA) of the influenza virus is in eight separate segments (genes). If a cell is co-infected by two viruses of different genetic make-up, then the eight segments can “mix and match” so that a virus with a new combination of the eight segments is produced. This is called reassortment. Some of the new viruses produced, which bud from the host cell, may have copies of the original genetic material from either of the original invading viruses.
Genetic material can also recombine to produce hybrid forms of genetic code that come from two different sources. In the case of influenza virus, one of the RNA segments might exchange pieces of itself with another segment or with the corresponding segment from a co-infecting virus. This would cause the newly formed virus to have sequences from two or more genetic segments.
All strains of flu are capable of undergoing specific mutations and reassortment. This can create variations which can infect species that were not previously known to carry the virus. This can also cause “harmless” forms to become deadly and reach pandemic levels.

What are all genes in its genome?

Lindsay Berman writes: The eight RNA segments are: HA, NA, NP, M, NS, PA, PB1, and PB2

What are their functions?

Lindsay Berman writes: The Influenza A virus genome is contained on eight single (non-paired) RNA strands that code for ten proteins. These proteins are necessary for viral reproduction.
o HA encodes hemagglutinin. About 500 molecules of hemagglutinin are needed to make one virion. The extent of infection into host organism is determined by HA. It is found on the surface of the influenza viruses. It is responsible for binding the virus to the cell that is being infected. The name hemagglutinin comes from the protein's ability to cause erythrocytes to clump together.
o NA encodes neuraminidase. About 100 molecules of neuraminidase are needed to make one virion. Neuraminidase has functions that aid in the efficiency of virus release from cells.
o NP encodes nucleoprotein. A nucleoprotein is any protein which is structurally associated with nucleic acid (either DNA or RNA).
o M encodes two matrix proteins (the M1 and the M2) by using different reading frames from the same RNA segment. About 3000 matrix protein molecules are needed to make one virion. Matrix proteins are structural proteins linking the viral envelope with the virus core.
o NS encodes two distinct non-structural proteins by using different reading frames from the same RNA segment. It appears to be a key regulator of protein expression in infected cells.
o PA encodes an RNA polymerase. Polymerase is responsible for reading the genetic code.
o PB1 encodes an RNA polymerase and PB1-F2 protein (induces apoptosis) by using different reading frames from the same RNA segment. PB1-F2 appears to enhance virus-induced cell death in a cell type-dependent manner.
o PB2 encodes an RNA polymerase.

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