Wednesday, April 27, 2011

Influe"N"za- and you

If you were a victim of the 2009 H1N1 outbreak, you are familiar with influenza's right-hand protein, neuraminidase. While you were coughing, wheezing, aching and exhausted, neuraminidase was throwing a rave in your respiratory tract. This essential protein maintains the life cycle of the influenza virus by allowing newly made viruses to leave the cell, as shown below:


Specifically, neuraminidase is a structural glycoprotein that cleaves the interaction between hemagluttinin (the "H" in H1N1) and sialic acid. It facilitates the removal of the viral particles by removing the N-acetyl nueraminic acid receptor, shown in the following reaction:


Neuraminidase exists of a tetramer of the following subunit, shown here in two different views:




The sialidase activity of neuraminidase has been found to be active even under very acidic conditions (pH 4.0), which may have contributed to the severe virulence of the 1918 "Spanish Flu" pandemic. Because the influenza virus can mutate efficiently and effectively, the chances are increasing that a more dangerous form of the virus will soon emerge. Neuraminidase inhibitors (anti-flu drugs) such as Oseltamivir and Zanamivir are becoming more available for use against this protein, but until we can find an effective way to stop it, we will forever live in fear of the next influenza pandemic. 

Neuraminidase is a fascinating glycoprotein, but its dangerous enzymatic activity has forced it to become a terrifying monster lurking in the shadows. So the next time you are lying in bed for days feeling horribly, you can ponder the power of neuraminidase and knowledgeably inform your caretakers of its activity within your body. I'm sure that they will be most grateful!!

References:

Takahashi, T., Y. Kurebayashi, K. Ikeya, et al. The low pH stability discovered in neuraminidase of 1918 pandemic influenza A virus enhances viral replication. PLoS One 5(12): e15556.

Tisoncik, Jennifer, Ying Guo, Katie Cordero, et al. Identification of critical residues of influenza neuraminidase in viral particle release. Virology Journal 8(14).

Zhang, C., Y.L. Cao, W. Zhong, et al. Establishment of a cell-based 2009 H1N1 influenza neuraminidase inhibitors evaluation systemYao Xue Xue Bao. 45(3): 383-387.