Some basic (biochemistry) comments about H1N1 virus.


 

 

This picture represents an Influenza virus.

 

Observe the capside and the core, containing nucleic acids associated to proteins.

 

The genome of the Influenza A virus is formed by 8 segments of negative sense RNA. Negative sense means that the molecule runs from 3’ to 5’, so it can not be translated to proteins. This type of virus needs a RNA polymerase for the transcription of the original viral RNA to RNA with positive sense (5’3’) that can function as mRNA.

 

Observe also in the viral surface two important glycoproteins: Haemagglutinin and Neuraminidase (Sialidase).

 

Hemagglutinin is a kind of lectin. Lectins are glycoproteins related to cellular recognition. Hemagglutinin in viral capside allows the virus to bind, in lungs and throat, with sialic acid residues (derived of neuraminic acid) that are part of the proteins in the epithelial cell surface. An endocytosis process allows the transport of the virus inside the cell and the eventual replication of the virus.

 

Once the viruses have been replicated inside the cell, they are excreted from the host cell inside a spherical phospholipid membrane that contains Hemagglutinin and Neuraminidase.  In the same say that happened at the beginning of the infection, the Hemagglutinin binds to sialic acid residues, but the Neuraminidase hydrolyses the glycoside linkage between Hemagglutinin and the Sialic Acid residues.

 

N-Acetyl-Neuraminic Acid (Sialic acid)

N-Acetyl-Neuraminic Acid (Sialic acid)

 

General Action of a Glycosidase (Neuraminidase is a Glycosidase)

General Action of a Glycosidase (Neuraminidase is a Glycosidase)

 

In the absence of the viral Neuraminidase, the new formed viruses would remain linked to the sialic acids residues in the cell surface or in the glycoproteins in the respiratory tract mucus, and they would get trapped and impeded of infecting other cells. 

 

Hemagglutinin (H) and Neuraminidase (N) also show antigenic properties and Influenza A viruses are classified in subtypes according to the kind of antibodies that these proteins raise. Sixteen subtypes of H (HA) and nine types of N (NA) are known. The Influenza virus H1N1 is then the Influenza A virus with Hemagglutinin subtype H1 and Neuraminidase subtype N1.

 

This picture, from the Influenza Laboratory of the CDC shows the Influenza A H1N1 virus.  (Compare the picture with the graphic shown at the beginning of this post).

 

 

The drugs Oseltamivir (Tamiflu®) and Zanamivir (Relenza ®) have been effective in the treatment of infections with H1N1 virus. These antiviral drugs are potent competitive inhibitors of Neuraminidase, particularly when they are used in the first 48 hours after illness onset, e.g., before the virus is able to release itself from the initial host cells and infect other cells.

 

Updated CDC recommendations about the use of these antiviral agents can be found in these links:

 

 http://www.cdc.gov/h1n1flu/antiviral.htm

 

http://www.cdc.gov/h1n1flu/recommendations.htm

 

This graphic represent the structure of Oseltamivir

 

 

In fact, Oseltamivir is a prodrug (a precursor of the active drug), since the  carboxylic ester linkage is hydrolyzed in the liver, so Oseltamivir becomes  Oseltamivir carboxylate, the active form, with a conformation that looks like the natural substrate of the enzyme, the N-acetyl-neuraminic acid, a form of Sialic acid)

 

 

Updated information about Influenza A H1N1 virus, can be found at the CDC site

 

CDC: H1N1 Flu (Swine Flu)

 

This is the official site of the Mexican government with news and recommendations about the Influenza (in Spanish):

 

http://portal.salud.gob.mx/contenidos/noticias/influenza/profesionales_salud.html

3 thoughts on “Some basic (biochemistry) comments about H1N1 virus.

  1. Pingback: “Potential risks of squalene in flu vaccine worse than the flu” « Complementary Medicine’s Weblog

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