Nucleic Acid Aptamer Selection Against Hemagglutinin for the Inhibition of Influenza Binding Capabilities to Human Cells

Nucleic Acid Aptamer Selection Against Hemagglutinin for the Inhibition of Influenza Binding Capabilities to Human Cells

The H1N1 Influenza virus, along with many other flu strains, is very easily transmissible and presents a range of symptoms that includes fever, mild respiratory infections, and some severe respiratory complications such as pneumonia that can lead to death (3). Along with seasonal epidemics in several countries, a few of the strains have created pandemics such as that of the H1N1, killing some 20 million people in 1918 (1). This RNA virus replicates itself in the human body by first binding to sialic acid sites on erythrocytes and epithelial cells, causing the host cells to agglutinate (4).

The Hemagglutinin (HA) Influenza protein is the surface-binding protein that the virus uses in attaching to host cells, and is dubbed after its mechanism in agglutinating red blood cells into visible clumps (1/2). HA is made up of two different types of chains, one that detects sialic acid on human cell-surface glycoproteins, and another that facilitates in the attack and agglutination of cells. The severity of each strain of influenza is based on the slightly different structures of the HA protein, however in general, the HA protein is the only method by which the flu virus can bind to host cells and begin replication and agglutination (4).

The HA binding protein is essential for the influenza virus, and without it, there is no host cell for which the virus can tether itself to for mass RNA replication (1). By understanding the binding properties of Hemagglutinin proteins, a nucleic aptamer can be developed in order to inhibit the HA protein from binding to host cells. Such a therapeutic aptamer can be used to contain seasonal epidemics and worldwide pandemics, thereby lifting public health standards and possibly pave the way for the inhibition of future mutated strains of HA.

Specific Aim 1: Selection of RNA Aptamers against Hemagglutinin

As stated, HA is a crucial surface-binding protein for the influenza virus to attack the cells of the human body and propagate the replication of the virus throughout. The protein has sequences that make up the head, which fits into sialic acid sequences of human cells like a lock and key (2). In this case, an aptamer can be developed in order to alter the confirmation of the HA protein, or attach to the fusion peptides of HA, thereby preventing sailic acid from binding to the protein (1).

The H1 strain of the hemogglutinin protein can be purchased through Immune Tech Corp (http://immune-tech.com/) for the price of $349 per 100 ug. The catalog number for the order is IT-003-00101∆TMp.

Bibliography

1. Goodsell, David (2006). “Hemagglutinin.” Protein Data Bank. PDB 101 Molecule of the Month.

2. Lin Tianwei, Wang Gengyan, Li Anzhang (2009). “The hemagglutinin structure of an avian H1N1 influenza A virus.” Virology 392 (2009) 73–81.

3. Hunt, Margaret (2010). “Virology Chapter Thirteen Influenza Virus (Orthomyxovirus).” University of South Carolina School of Medicine. Microbiology and Immunology Online.

4. Cerchiara Jack, Holsberry Brendan (2006-2007). “Hemagglutinin (HA) - Cell Binding protein in Avian Influenza.” Kenyon College Department of Biology.

10 comments:

Zoe White said...

Sounds like a good current events aptamer!

-Zoe White

Austin Rezigh said...

Good job Shaan. A very original target and a project that holds great value if successful.

Have you looked into the structure of this protein yet? If so, do you the "fusion peptides of HA"? It might be interesting or useful to do a sort of double selection on these and the target in order to develop an aptamer that binds specifically to these fusion peptides.

Sravani Mannuru said...

Great target - influenza seems to always be a relevant issue. Good luck!

Arsany Gadallah said...

I like your project. The abstract is straightforward and focused. Your figure is not there but I have seen your target in lab....in 3d so it's all good

Alec Rezigh said...

Nice job, Shaan. This was well written. Have you checked to see if the protein is pathogenic and safe to use in the lab? Besides that, well done.

Shaan said...

Hey Alec, yeah I need to look more into like a video or something of how exactly this protein undergoes its changes in conformation. If you look at one of my links, it shows kind of like a step by step of how HA changes in conformation before and after it binds to the host cell. However, (and this is just my understanding I may be wrong) the fusion peptides are contingent upon the activity of the overall HA protein itself. It's some weird stuff how the fusion peptides are very undefined in the protein itself, and then just...magically jut out of the protein and serve as the primary method of binding. I don't know I'll have to look more into this....

Shaan said...

Oh sorry the previous post was to answer Austin's question. But yeah Alec I think the HA protein is harmless without the virus itself....not sure i'll have to check...

Michael Ledbetter said...

Good work on the abstract. I was curious isn't part of the problem with developing flu vacines their high mutation rate? Is Hemagglutinin a fairly conserved protein?

umar.ahmad said...

Solid target. Probably one of the most relevant/applicable targets proposed.

Cody Grissom said...

I like the application of your target and how it plays in with current epidemiological issues. Great work!