a briefing document
on serious responses to flu and tamiflu effects
protein amino acids
antigenic shift - explaining labels like H1N1
how coding for mutations work - the position numbers can also change through mutation
non-covalent forces holding together antigen/antibody complex
for endless hours of fun - folding virus proteins
In part, I am assembling this page to allow intelligent readers to find their way more easily through the jargon-loaded sources on the area of immunology. Secondarily, this page provides summary notes from all my wading through book and journal sources.
A fundamental idea is to think in terms of keys and locks. These can be both ‘one’-dimensional and three-dimensional. On this page, I shall deal only with the three-dimensional type. While the examples used on this page relate primarily to influenza, the mechanisms in this area are widely applicable, say to vaccinations, medicines and immunology theory.
Summary from three recent studies.
There are two main strains of flu virus, named A and B. A includes the H1N1 strain. Meanwhile, flu mutates like billyo in normal circumstances.
The present main concerns are with the recent H1N1 strain (‘swine flu’) and Tamiflu.
Once it is decided which strain of flu virus is being discussed, then suitable treatments can be suggested, but as the window is longer than testing times and there are several variants around at any one time, it is a matter of guesswork which vaccinations or anti-virals are relevant.
Tamiflu is a neuraminidase inhibitor. There are two of these so far FDA approved, with trade names Tamiflu and Relenza. There are two other treatments used for flu called adamantanes, they are Amantadine and Rimantadine. These latter two are not deemed useful for B viruses (H1N1 is an A virus), and the H3N2 virus currently circulating is resistant to them.
As you will have noticed, there was an H1N1 virus around last year that was resistant to Tamiflu, while the present H1N1 (‘swine flu’) resistance has not been found - yet. The ‘N’ molecule (neuroamidase) is made up of about 467/8 amino acids. Now these complex (neuroamidase) molecules fold predictably according the amino acid sequence. Keeping in mind that the flu virus relies on rapid mutation, certain random changes in the amino acid sequence can result in the Tamiflu molecule not fitting tightly enough, or as accurately, and thus may fail to block/disrupt the neuroamidase action of the virus. This is approximately how resistance to a substance like Tamiflu develops.
Of course, a change in the neuroamidase may also make the virus ineffective - typical evolution in action. Meanwhile, the biochemists are understanding the little beggar ever better and are working on improving the inhibitor molecules and on developing new attacks on the virus.
These drugs are fall-backs if vaccination does not work, or if the current flu version gets a start. (It takes about six months to obtain a useful vaccine.) Each year, the medical warriors are trying to keep ahead or get ahead of flu, but flu is a very crafty and agile monster.
Proteins are built of long chains of amino acids.
Here is a schematic of the general amino acids structure:
There are twenty different types of R side chains, each with a different structure, making twenty amino acids. The R side chain is attached to the central carbon [C].
The twenty different R side chains are divided into nine nonpolar, six polar, two acidic electrically charged, three basic electrically charged.
Amino acids link together in long chains by peptide
bonds, a special covalent protein bond. (A covalent protein bond being a type of chemical bond where two atoms are connected to each other by the sharing of two or more electrons.)
These chains can be very long and, at body temperatures, they fold predictably into shapes of varying complexity.
Antigenic shift happens when a virus manages to swap a complete RNA strand. This happens when two substantially different variants of the virus enter into the same host. For instance, antigenic shift occurs when an avian RNA strand replaces its equivalent strand in a human flu virus while both are inside a pig. When this shift happens, it becomes particularly difficult to predict what delightful surprises the new virus may have in store.
Thus you may hear references to H1N1 flu, H5N1 flu etc., referring to the two first strands listed above. These are the genes expressed on the surface of the virus, and are, thus, most relevant to immune system response.
From an excellent and clear discussion of flu virus resistance through mutation, relative to Tamiflu (Oseltamivir). This is a useful page to see how the research is put into context.
From the World Health Organization - a revision of the system of nomenclature for influenza viruses, WHO Memorandum Bulletin 58 (1980) 585–591:
It is important to keep in mind that the sum total of mechanisms looked at on this page (and there are others) mean that this area of science is becoming immensily complicated - and therefore interesting! - and that mechanisms are not just on-off. For example, the ligands have a very wide range of stickability, and the keys and locks vary in fitability as you will realise if you do real hard work on the above.
endless hours of fun - folding virus proteins
email abelard at abelard.org
© abelard, 2009, 20 october
the address for this document is http://www.abelard.org/briefings/immunology.php