Retroviruses

- So you might have an understanding of viral replication, but there's one special case that doesn't quite fit neatly into the box of lytic or lysogenic. And that's what we're going to talk about. So that special case is called a retrovirus. So first let's zoom in and take a look at some unique things about the retrovirus that make it different from other viruses. So first of all, it is an enveloped, single-stranded RNA virus. And inside of this envelope it also carries three special proteins. And right now just be aware that they are three special proteins. I'll talk about them more when we get to each step where they're important. So as you know, enveloped viruses can enter in one of two ways, either through tricking receptors, receptor-mediated endocytosis, or through direct fusion. And it just so happens that in our example, and we're talking here about the retrovirus HIV, this retrovirus will enter the cell with direct fusion. So now that this nucleocapsid is inside the cell, it actually has to undergo a step called uncoding where this purple capsid is dissolved. Oh, and we forgot about the protein, so let me redraw those in right now. So these are the proteins that were originally inside of the capsid. So everything inside of that coat is released. And this is where the first special step occurs. So we're going to say that this red protein is reverse transcriptase. So reverse transcriptase will hop on to the RNA, and it reverse transcribes the RNA, which means that so it reads from five prime to three prime end. And you will form complementary DNA shown here in pink. And the reason it's called reverse transcription is usually you take DNA to make RNA. But in this case you take RNA to make DNA. And because this is the complementary DNA strand, we call this cDNA, complementary. And then reverse transcriptase will work again on this same RNA to make another cDNA strand. Because it's the same exact code, it can recombine with the other cDNA strand to make a double-stranded DNA. And so now what happens is you have integrase coming along. And let's make integrase blue. So integrase comes along, clips off each of the three prime ends. So now these are slightly shorter on each end. And sorry this is a bit hard to see because this strand's three prime end is over here. And while the first one is actually clearly labeled as this is the three prime end. And by clipping off those three prime sections, they form these sticky ends because unpaired DNA wants to be paired. And integrase has suddenly removed that part. And you might be wondering what happens to this RNA. And what happens is that it actually gets degraded by normal ribonuclease. So that's no longer there. And integrase does exactly what it says. It will follow this path and integrate this HIV DNA into the host's DNA. And one thing I would just want to very quickly mention is that if I had drawn this to be super accurate, this would need to have a nucleus around it because the HIV retrovirus infects human eukaryotic cells which have a nucleus. So it actually will travel through the nuclear membrane to get to the genome. And here integrase helps the viral DNA integrate with the host, like its name, integrase, integrate. So just imagine this is all double-stranded, but just for simple drawing sake, this will just be one line. So this is viral DNA. And this is called the provirus stage. So you can see that this is similar to the lysogenic cycle that we'd talked about before. But unlike the regular lysogenic cycle, it's not dormant or latent. It actually does not have that repressor gene that typical lysogenic viruses have. So it is actively transcribed whenever the host's DNA is transcribed. So since the host's cell thinks this is normal DNA, it will make RNA. And I just wanted to call this viral mRNA so you have an idea that the cell cannot tell that this mRNA shouldn't have happened. So this mRNA exits the nucleus. And these viral RNAs are now in the cytosol. Again, once this viral mRNA exists the nucleus and it goes into the cytoplasm, it's just like any other RNA. And some of these will be translated into proteins like the capsid proteins. And of course the three proteins that we begin with which are the reverse transcriptase, the integrase, and actually the last one we haven't yet mentioned, is the protease. The green here is protease. And we're going to hold off a little bit on what protease does. But here it's formed. And you can see that you now have all of the parts that can self-assemble into new viruses. So again, all of these viruses that are formed will have the RNA, the reverse transcriptase, the integrase, and the protease. So you'll notice that these are actually missing one thing. They're missing their envelope. And so they're called immature viruses. And unlike the typical lytic cycle, it doesn't just break open the membrane. In fact, it takes advantage of the membrane. And so these viruses will come along, and they will bud off. So this will want in here and this will want to enter here. Oops, and that's missing a border, I just realized, so there you go. And they will bud off, and that will be their envelope. And sorry, they're missing the proteins. And I'll just draw them in again. So again, these are still immature, right. And before they go on to infect other cells, they have to mature somehow. So what happens is that protease inside of here will cleave those other proteins to make sure that they're fully functional before the virus enters another cell and starts this cycle all over again. And so retroviruses replicating are a bit more complicated than traditional replication. So it's not just lysogenic or lytic. It actually has elements of both.