 Everybody, Dr. O'Hare. This is what we're going to talk about HIV, so we're going to talk about the structure of the virus, its routes of transmission and then how it infects an individual CD4 positive T cell. So here these little green dots are the HIV virus, let's get a little bit of a more close up look. So this is an example of HIV, as you can see from the top, it's called a retrovirus. Let's talk about just viruses in general. So viruses are going to basically be a protein coat with genetic material inside of them, either DNA or RNA. So HIV is an example of an RNA virus. Some viruses like this one are going to have a lipid envelope around them as well. So that's what you're looking at here, just a typical looking virus. What makes HIV special and pretty unique is that it's a retrovirus and so when I think of retro, I think of backwards or behind, right, and that's basically where the name comes from. So HIV, there are other retroviruses like hepatitis C, but HIV as you can see here is an RNA virus, nothing unique about that. What makes this special is going to be reverse transcriptase, those little red balls there, the enzyme. So transcription is the conversion of DNA into RNA. So reverse transcriptase is an enzyme that turns RNA into DNA and you're going to see that's a super important as far as how HIV gets into your cells and how it hides inside your cells. So we'll come back to that in a moment. So this is an RNA virus, it's a retrovirus, we covered all that. The last important feature that will help you understand how the disease is, how it infects our cells, is those glycoprotein spikes on the right-hand side. So there are going to be a couple numbers you're going to see. The ends of these spikes are called GP120, the stock will be GP41. So both of those do play a role. I'm not a huge stickler for numbers like that, but I just want to make sure you understand where those numbers come from. So all right, that's the basic structure of the virus. As far as how it's transmitted, HIV can survive about six hours outside of a cell. It can survive inside a cell for more than a day, day and a half, somewhere in there. But as far as how it's transmitted, we generally think of it as a sexually transmitted infection. Also, you think about like sharing needles, so contaminated needles can be one. So we have sexual transmission, different types of sexual transmission, transplantal, so moms can give them to their babies across the placenta. It can also contaminate breast milk, organ donation and blood transfusion. That's still a problem in some areas, but that's why in the U.S. these things are screened for the HIV virus. So that was a huge deal back in the past. There was the Ryan White story was a movie that was real popular when I was a kid. He had hemophilia and he got HIV and ended up dying of AIDS from his blood transfusions. So the most dangerous form of contact or the easiest way to contact the disease is from anal-receptive intercourse. It just has to do with the fact that there's going to be more blood transferred and things like that. So all right, so that is the basic structure of the virus and then it's how it's transmitted from one person to another. Here we see the actual infection process. So I'm just going to go number my number here. I know this is kind of confusing. You may want to watch this a couple of times, but because this will teach you not just about HIV, but about how viruses work in general and specifically your retroviruses. So number one, the HIV fuses to the host cell surface. And that's why HIV is only looking for CD4 positive cells. So the T cells are going to be the big ones. Your helper T cells, specifically they're called CD4 positive helper T cells. But macrophages and then dendritic cells, which are other antigen presenting cells, can also be infected. But we're primarily going to focus on the CD4 positive helper T cell. This is why HIV does not infect your CD8, your cytotoxic killer T cells. It's also why HIV doesn't infect all your other cells, right? If HIV was less discriminatory and went after all your cells, it would be ebola. It would kill people in a matter of days as it turned their bodies into soup. So the fact that it only goes after certain cell types is why you can survive for years with this infection even without treatment. The bad news is it happens to pick, what I would say is the most important immune cell we have will cover the immune system in other units. But the helper T cells, I call them the generals in your infection, your immunity army because they are needed to activate your cytotoxic T cells. So your T cells can go and do combat. But they're also needed to activate and sensitize your B cells. So they're responsible for both arms of your adaptive immune response. And so they're a bad cell target for sure. So the HIV virus is looking for that CD4 receptor. And you can see that it docks there. But then you also see that it takes a co-receptor. And there are two different ones, CCR5 and CXCR4. The CCR5 is by far the most important because there's a subset of the human population, especially people from like Northern European descent, that are missing the functioning CCR5 co-receptor, which means that they are immune to some strains of HIV. So I'm very cautious about how I say that because there are people with this mutation that have still gotten HIV. So it makes you much less likely to get some strains of HIV. But the other strains could still actually infect you. So I would never tell anyone don't worry about HIV because of this mutation. But it's important because not only are there some people that are immune to some strains of HIV, but they're working on drugs. And they have drugs that can block this co-receptor to try to give other people the benefit of missing this co-receptor. So that's the GP120 protein piece there is attached to the CD4. And then you see in the next picture over, it's docking on that co-receptor as well. And then now, step two. So the HIV, what's inside the HIV virus, which is the RNA, the enzyme-reversed transcriptase, the enzyme integrase, which we'll talk about in just a moment, and other components get dumped into the cell. So this process takes the other, that GP41 that I talked about earlier, and that's going to be important later because we do have fusion inhibitors. There are drugs that will try to stop this process. Number three, so it says here the viral DNA is formed by reverse transcription. And remember that HIV is an RNA virus, but it has the enzyme-reversed transcriptase that turns it into DNA. So now the viral RNA has been turned into DNA. Step four, viral DNA is transported across the nucleus into the inside of the CD4 positive T cell. And integrates into the host DNA. So that's going to be where that enzyme integrase, as you can see here, is being used. So the enzyme integrase will take this newly formed HIV viral DNA and cram it into the genetic material of the cell. Once this happens, this cell has become, basically become a factory, or at least a potential factory for churning out HIV viruses. There's also at this point no way to save this cell. It's become part of what this cell is. All right, so what I said it could be a factory, or it is a factory, it could be because some of these cells are latent and they're not actually going to be churning out viruses, but they now have the ability to do so. Okay, so the cell has, it's found its target, the CD4 positive T cell. It's fused with it, it's dumped its payload inside the cell. The RNA has become DNA and now it's been used with the use of integrase, has been crammed into the DNA of this cell. So this cell can't be saved. The key is, can we slow down this process as the virus has come out of the cell? So step five, now this cell is a factory making HIV viruses. So step five, new viral RNA is used as genomic RNA and to make more viral proteins. So this is going to be where RNA viruses are being produced, at least the packaging is going to go in them. And then to make the viral proteins, that's important too, because you're going to see that one of the classes of drugs that's used to fight HIV is protease inhibitors. Can we stop these newly produced proteins from becoming functional? So that's one of the many drugs you'll see in the drug cocktail that's being used to help people that have HIV. All right, so step six, we're just about there. New viral RNA and proteins move to the cell surface and they form a new immature HIV virus forms. Reason that's important is because we now have maturation inhibitors. We have drugs that can hopefully stop it from fully maturing. And then step seven, the virus matures when the proteases release the proteins that form a mature HIV. And then it's going to leave this cell and go and infect another CD4 positive T cell. And thankfully, we keep working on treatments because now there's a class of drugs called tetherins that will try to keep that mature virus from actually being able to leave this cell and go and infect another one. So we're doing really well. If you think about it, we'll talk about the treatment in a separate video, but it's pretty amazing how this HIV has went from a serious killer to a much more manageable chronic disease. Like I was telling some students in the class recently that if you were 45 years old and you were diagnosed with uncontrolled type 2 diabetes and HIV, the diabetes may kill you first. Like that's where we're at because these drugs do work. So in another video, we'll talk specifically about how drugs block each one of these steps. That's why it's so important for you to understand how the virus works so we can combat it and stop it from doing its job, which is to infect us and then infect more of ourselves. And then hopefully for its sake, find a way out into other human beings. Okay, that is the HIV virus and how it works. I hope this helps. Have a wonderful day. Be blessed.