“And bingo. Dino. DNA.,” proclaimed the DNA molecule, which was followed by some congratulatory music. Ian Malcolm (Jeff Goldblum) leans forward in his chair with a large grin plastered on his face. Alan Grant (Sam Neil) returns the smile and looks back to the screen.
Yes, that is a scene from Jurassic Park the movie. I’ve seen it a time or two. I’ve also read the book a few times. It’s really a very wonderful story, except for all those deaths and the grand ego of the initial idea holder, John Hammond. Oh well. The helicopter ride looked cool.
I’m sure you will recall that scientists in Jurassic Park found dinosaur DNA in a complicated place: the blood held within the abdomen of a mosquito which had fed on a dinosaur, but then met a sticky end by becoming overcome with tree sap that eventually solidified into amber. Whew. That’s a lot of coincidences, if you ask me.
Interestingly, scientists hunting for the 1918 influenza virus also relied on some coincidences and fortuitous timing to obtain their query. Unfortunately, they sought the intact virus, which was unable to be obtained; they had to be content with discovering viral RNA. As you will see, viral RNA contains a lot of useful information for rebuilding parts of this deadly virus.
Viruses are stealth. They are small, carry only necessary equipment with them, and blur the line defining what scientists classify as “alive.” Figure 5.1 shows a generic virus. While drawn much like a cartoon, the major points of the virus are well represented. The blue and red “spokes” poking out are viral coat proteins, which enclose the inside of the virus, protect the genetic material, and are responsible for binding to cells then securing viral entrance. For influenza, these coat proteins are known as hemagglutinin (discussed in Spanish Influenza Part 1) and neuraminidase. Coat proteins are also recognized and remembered by our immune systems in the form of antibodies. Should your body become infected again with a virus it has already encountered, typically your immune system will remember and vanquish the invader swiftly.
The inside of our cartoon shows lots of coils. These coils represent the viral DNA. Since we all now know about the central dogma (see previous post of the same name), we understand that DNA carries all the information for making proteins. When a protein is needed, the DNA encoding this protein (called a gene) is copied into an RNA molecule then translated by a ribosome to make the protein.
A human cell’s DNA molecule encodes for thousands of proteins. In contrast, a viral genome encodes for very few proteins. For example, the human papillomavirus (HPV) genome encodes for seven proteins. Seven! How does a virus get away with this?
If you read the post called Spanish Influenza, Part 1, you’ll remember that I said viruses want to break into our cells and steal our cellular machinery. Human cells are rather self-sufficient: they have RNA bases floating around to be incorporated into new RNA molecules, they have amino acids ready to be strung together to make proteins, they have ribosomes waiting to read RNA molecules, etc. Viruses do not have these things! They carry a genome, which dictates how to make viral proteins, but they are completely unable to make these proteins on their own. They must gain entrance to a cell and use the cell’s RNA bases, ribosomes, and amino acids to make their proteins. Viruses are like bakers with no bakery.
In essence, when we are infected by a virus, the virus breaks inside our cells and overtakes our protein-making machinery. Instead of making cellular proteins, the infected cell is instead churning out viral proteins.
If our scientists could get their hands on some cells infected by the 1918 influenza virus, they would find a tremendous amount of RNA in the cell that is encoding for viral proteins. RNA molecules encoding hemagglutinin and neuraminidase, among the other influenza proteins, could be sequenced and then translated. From that information, they would have the amino acid sequence for the proteins and could begin to compare them to hemagglutinins and neuraminidases from other influenza viruses. How do they compare? Same amino acids? Different? By asking the correct questions, scientists can begin to tease out what made this virus so deadly and, possibly, preemptively identify similar characteristics in current influenza viruses.
Several papers discuss the patients from whose tissue samples influenza RNA was able to be extracted. I will summarize below, but suffice to say, the information came from very interesting places!
- - 21 year old male, admitted to the Fort Jackson, South Carolina army camp hospital on 9/20/1918. He died six days later suffering from influenza, bacterial pneumonia, and cyanosis. His body was autopsied and some tissue samples were formalin-fixed and embedded in paraffin.
- - 30 year old male, admitted to the Camp Upton, New York army camp hospital. He died after three days of acute respiratory failure. During autopsy, some tissue samples were formalin-fixed and embedded in paraffin.
This last place is the most interesting of all!
- - Teller Mission (now called Brevig Mission) was ravaged by the 1918 influenza. Located on the Seward Pennisula in Alaska, 85% of the adult population was killed (72 people) in five days. A mass grave in the permafrost was used for all the dead. In August 1997, several bodies were exhumed and lung tissue was biopsied for influenza RNA. One Inuit woman (of unknown age) provided the best sample for extracting RNA.
From here, a known protocol was used to recover the RNA from fixed cells, amplify the results and obtain the sequences for both hemagglutinin and neuraminidase. Several studies went on to compare the sequences with other known sequences, some also tried to rebuild an influenza 1918 virus and study its characteristics, and some actually studied what the individual proteins looked like in three dimensions. This is where our next Spanish Influenza post will lead – we will look (with colorful pictures!!) at the three dimensional structure of 1918 hemagglutinin.
Gene: a stretch of DNA which encodes for a particular protein
Cyanosis: blueness of the skin due to lack of oxygen in the blood
Formalin-fixed: Fixation preserves tissue from decay or damage and allows for further investigation of the cells.
References
Crichton, Michael. “Jurassic Park.” (1990) The Random House Publishing Group, New York.
Spielberg, Steven. (1993) “Jurassic Park.”
http://www.cdc.gov/flu/images.htm
Reid et al. “Origin and evolution of the 1918 ‘Spanish’ influenza virus hemagglutinin gene.” (1999) PNAS 96, pgs 1651 – 1656.
Reid et al. “Characterization of the 1918 ‘Spanish’ Influenza virus neuraminidase gene.” (2000) PNAS 97(12) pgs 6785 – 6790.
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