A better understanding of how Flu invades our bodies and cells helps give us better insight into prevention and mitigation

This is a very good article on the NSF website and research work on understanding common flu and also possibly H1N1 and other variants.


In order to infect a healthy cell, a flu virus must enter the cell (upper left) and empty viral genes into it. First, the virus binds to the cell. Then it becomes enveloped inside a bubble called an endosome as it gets taken into the cell. It is acidic inside the endosome–more acidic than the interior of the virus it contains. This pH difference serves as a signal to the virus that it is inside the cell, so it is time to release the viral genes (shown as orange squiggles). It is the M2 proton channel that helps the virus sense this difference in acidity and trigger the release of viral genes into the cell. Since the cell cannot tell the difference between its own genes and those of the virus, it gets tricked into making copies of the virus which can eventually go on to infect other cells.
Credit: Nicolle Rager Fuller, National Science Foundation

I literally copied parts of the text from NSF website. There is a lot more to read if you click on the link. Also there is a video on this site that’s worth watching.

If this already made you curious, please go to NSF website to read the rest of the article or read some of the excerpts below and then go to the NSF site.

TheMei Hong, a chemist at Iowa State University, uses NMR to study a proton channel named M2, found on the surface of the influenza virus. This proton channel has been the subject of numerous studies because of the key role it plays in helping a virus take over a healthy cell after it gets inside. In order to infect a healthy cell, a flu virus must enter the cell and empty viral genes into it. First, the virus binds to the cell. Then it becomes enveloped inside a bubble called an endosome as it gets taken into the cell. It is acidic inside the endosome–more acidic than the interior of the virus it contains. This pH difference serves as a signal to the virus that it is inside the cell, so it is time to release the viral genes. It is the M2 proton channel that helps the virus sense this difference in acidity and trigger the release of viral genes into the cell. Since the cell cannot tell the difference between its own genes and those of the virus, it gets tricked into making copies of the virus which can eventually go on to infect other cells.

"One can study the structure of proteins in many ways, but protons are difficult to visualize by X-rays," said Hong. X-rays are commonly used to study the structure of proteins in a crystal form. "We used NMR because we wanted to see where the protons are relative to the channel. Moreover, the state of the samples that we study using NMR is closer to the natural biological state than most other structure determination techniques."

Using NMR, Hong’s team was able to obtain evidence that the channel moves protons by the "shuttle" model. The work, published in the October 22, 2010 issue of the journal Science, shows that ring-shaped histidine molecules facing the pore of the channel are able to flip back and forth at more than 50,000 times per second when the channel is in an open state (imagine a windshield wiper-like motion).

After every few flips, the histidine is able to pick up a proton from outside the virus and flip it into the interior of the virus. Movement of protons into the virus causes the interior to become more acidic as protons accumulate. This serves as a signal that the virus is inside the cell, and it should release its genes–the next step in the viral infection process.

Amantadine and rimantadine, respectively known by the trade names Symmetrel and Flumadine, are two of the older antiviral drugs approved by the FDA. Both have been shown to make flu symptoms less severe and shorten the time it takes to get better.

Hong has also used NMR to learn more about amantadine, which prevents susceptible viruses from spreading. The study, included in Nature on February 4, 2010, showed that amantadine binds two different sites on the M2 protein. Combined with other data, Hong and colleagues concluded that amantadine physically blocks the M2 channel, preventing the movement of protons into the virus and subsequently, reproduction and spread of the virus.

Unfortunately, amantadine and rimantadine are no longer recommended for widespread use because many flu strains, including H1N1, are resistant.

Hong explained, "Since most flu viruses now have the mutation, we will focus on that next."

This research is very interesting and might lead to better ways to mitigate the flu effects even after the patient is infected and the incubation started.

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