Breakthrough in Virology

00:01 Now in the recent 10 years or so, a technology called next-generation DNA sequencing has been developed which has revolutionized every field of the life sciences including virology.

00:14 It is also known as deep high throughput sequencing because you can sequence a small amount of nucleic acid at a very high rate and you can get very accurate predictions of what the sequence is.

00:27 This has allowed us to identify new viruses in environmental samples and to identify new pathogens and we discussed many of these discoveries on my podcast.

00:38 You can find that TWiV.tv. You can also use deep sequencing for clinical purposes to identify pathogens in a very rapid and dependable manner.

00:49 Now, in the 1950s shortly after cell culture was developed as a viable way of studying viruses.

00:57 There was a virology breakthrough and that breakthrough was to finding that the nucleic acid genome in the virus particle is the genetic code.

01:08 Now this may sound not so interesting today because it's something we've been with for a long time.

01:13 But in the 50s, there's only a few years after we realized that the DNA in our cells was actually the genetic code.

01:20 So finding it out for viruses at that time was an important discovery.

01:24 And two different experiments went towards making this discovery.

01:28 The first shown on the left is called the Hershey-Chase experiment with phage T4.

01:33 This is named after the two scientists who did this experiment.

01:36 What they did is they labeled the various component with different kinds of radioactive isotopes.

01:42 They labeled the nucleic acid which is DNA for this bacteriophage or they labeled the proteins of the virus particle.

01:50 And then they infected cells and they asked which part of the bacteriophage entered the bacterial cell? And they found it was only the DNA that entered the cell, proving that the DNA is the genetic code.

02:03 On the right is a virus, tobacco mosaic virus which we've talked about in other lectures.

02:09 This was the first virus ever discovered.

02:11 Experiments on this virus in the 1950s by Frankel Conrad and his colleagues showed that the nucleic acid of that virus is the genetic material.

02:20 Tobacco mosaic virus has a genome of RNA not DNA as for the phage T4.

02:27 They extracted the RNA from this virus particle and showed that when it was introduced into cells it gave rise to new virus particles.

02:34 So the nucleic acid is the genetic code of all viruses.

02:40 Maybe even the bigger surprise as we discovered thousands and thousands of new viruses all over the world of all different shapes and sizes as you can see just a sampling of here.

02:52 We discovered that there's only a finite number of virus genomes.

03:00 And this really helps to study viruses, it makes it much less daunting.

03:05 And so for students of virology such as you who may be listening now, this discovery really makes your life easier.

03:13 And here are some key facts that really help that.

03:16 First of all, all viral genomes have to make mRNA – messenger RNA that can be read by the host ribosome.

03:25 No virus can make their own proteins. Viruses depend on a cell in order to do that.

03:32 So, every virus has to make messenger RNA and therefore that gives a commonality to all virus replication schemes.

03:42 Every virus that we know on the planet follows this rule. There's no exception.

03:46 They all have to make mRNA that can be read by host ribosomes.

03:51 Now Nobel laureate David Baltimore who won a Nobel Prize for discovering a viral enzyme called reverse transcriptase, he used this insight to describe a simple way to think about virus genomes.

04:06 He said, "Well, every virus has to make mRNA, so let's make a scheme for virus classification that puts mRNA in the middle and then let's trace how all the viruses get to mRNA." And when he did that, he found that there were only seven different types of viral genome and they're all shown here.

04:26 We have mRNA in the middle of the scheme, and then we have the seven different genome types around it.

04:32 We have double-stranded DNA or single-stranded DNA that's the types I and II.

04:38 Type III is double stranded RNA. Type IV is + stranded RNA. Type V is - stranded RNA.

04:47 Type VI is + stranded RNA with the DNA intermediate and type VII is gapped double-stranded DNA.

04:55 So the thousands and thousands of viruses can all be reduced to seven categories when you categorize them in this manner.

05:03 And furthermore, this Baltimore scheme as we call it lets you know only the nature of the viral genome and you can then deduce the basic steps that have to take place to produce mRNA.

05:15 And just as an example, if you have a single-stranded DNA genome, we know that mRNA cannot be made from single-stranded DNA, so the next step has to be making a double-strand intermediate as you can see on the slide and then finally messenger RNA.