Positive-sense Single-stranded RNA ((+)ssRNA) Virus – RNA Virus Genomes

00:01 We now move onto viruses with single-stranded RNA genomes, and we are going to look first at those of positive polarity, this is mRNA sense polarity. One family, the Picornaviridae, contains the important pathogen poliovirus, about to be eradicated. It would only be the second virus to be eradicated after smallpox. The Caliciviruses, if you've ever gone on a cruise and gotten diarrhea, you can thank the caliciviruses, in particular Norwalk virus.

00:30 They cause outbreaks of diarrheal disease on cruise ships, schools and colleges, any institutional setting. Then we have the Coronaviruses. The SARS coronavirus came out of China and caused a global outbreak in the 2000s, the MERS coronavirus currently causing outbreaks of serious respiratory disease in the Middle East. Looks like it goes from camels to people.

00:59 The Flaviviruses have a number of substantial human pathogens, yellow fever virus, mosquito transmitted liver disease, West Nile virus, also mosquito transmitted, hepatitis C virus are examples of Flaviviruses. Flavi comes from yellow, which is the color of someone who has yellow fever, because of the jaundice being caused by virus infection. And finally the Togaviridae has important viruses like rubella virus, and equine encephalitis virus.

01:31 So let's take a look at how these genomes replicate. Again, they are plus sense RNA genomes, you can see on the left part of the slide there, it's a green line shaded gray, that genome can be translated directly to make protein by the host cell, which can go on to assemble new virus particles. Of course just like every other virus we need to make additional genomes and so what happens is simply the plus strand is copied to make a minus strand RNA, you can see in yellow there, which is copied again to make more plus strands, and again, what enzyme does this? Is it a cell enzyme? Absolutely not! Cells can’t do this, it's a virus enzyme, and that minus RNA has no other function except to be a template for the synthesis of more plus strands. Now these viral genomes are naked in the virus particle, there's no RNA polymerase. Now remember the real virity with double-stranded RNA, they contain an RNA polymerase in the particle, because the double-stranded RNA could not be translated, these genomes are plus mRNA, they can be translated as soon as they get into a cell. so you don’t need to have a polymerase there. You can make the polymerase from translation of the genome. So this is what distinguishes the two kinds of RNA viruses with or without a polymerase, whether or not the mRNA is accessible by the host cell translation machinery. Now these single-stranded plus sense RNA genomes vary in size. The Coronaviridae are among the largest that we know of, 28 to 33 kb in size. And these are typical messenger RNAs, they have a cap at the 5 prime end, they're polyadenylated at the 3 prime end.

03:14 The Flaviviridae plus stranded RNA genome is somewhat smaller, 10 to 12 kb in length.

03:20 Again it has a Cap at the 5 prime end, curiously the Flavivirus genomes do not have a poly A at the 3 prime end. The Picornaviridae genomes are 7 to 8 and a half kb in length. They are polyadenylated.

03:33 But at the five prime end they don't have a cap, rather they have a small viral protein.

03:38 And finally the Togavirus plus stranded RNAs are from 10 to 13 kb long with a five prime cap and a three prime poly A tail.

03:48 Let's move on to single-stranded RNA viruses with a plus sense genome, except these viruses go through the DNA intermediate. And there is one virus family containing these kinds of viruses, it is called the Retroviridae or retrovirus family, and the picture of the virus you see here is an example of a retrovirus. There are two human pathogens in this family.

04:15 They're very important pathogens, one is HIV, human immunodeficiency virus, of course we’re in the midst of a huge HIV pandemic, over 33 million people are infected at this moment in time, and then the other human retrovirus, Human T-lymphotropic virus or HTLV, also causes millions and millions of infections as well. Now these are very unusual viruses, because they are plus stranded RNA genomes, but they go through a DNA intermediate. So you can see at the top is the plus stranded RNA, and here is an example of a plus RNA that is not a messenger RNA. It could be, it could be translated readily, but when this comes into a cell by a virus infection, it is not translated; it is sequestered from the host ribosomes, and instead is copied into a minus strand DNA by the enzyme reverse transcriptase. That enzyme, as I mentioned earlier, Nobel prize-winning discovery, was first discovered in the retroviruses and subsequently found to be in the hepatitis B viruses as well. Now you can predict what's going to happen next, because a minus DNA of course cannot be made into mRNA, you can only make double-stranded DNA into mRNA, so that minus DNA is made double-stranded, it can then be copied into mRNA which can be made into proteins. And to make more virus genomes, which are plus RNA, a subset of those messenger RNAs can simply be packaged.

05:52 So the retrovirus genome is shown schematically on the left of the slide. It is around 7 to 10 kb long and it's a typical mRNA with the five prime cap and a three prime poly A tail, and I say typical because again it is not translated when it enters a cell, it is reverse transcribed, and only later are the mRNAs translated when they are made from double-stranded DNA.