quizzing Public Health Friend about immunology and virology
He said, "I studied how this stuff works for 10 years and you want me to explain how it works in 5 minutes,"
Yes!
Here was my question: Why do we need a flu vaccine every year, but we only need the measles vaccine once as kids? Doesn't the measles virus mutate as often as the influenza virus?
It took awhile for Public Health Friend to get to my point. Yes, the measles virus mutates as often as any other RNA virus. But he wanted to explain the different survival strategies and host populations of the two viruses. He felt I was using his field's terminology too loosely.
But I'll get to my point. Both measles and influenza are RNA viruses and they both mutate a lot, on average once per new virus particle. But measles is built like a precision missile -- it is super infectious against human cells -- and so each copy of the measles virus either works the same or it doesn't. There's not really any room for mutations to make measles even better, or to change how it looks. It's too precisely-well designed for infecting human cells. Most measles copies don't work, because of mutations, but the minority of true copies are fuckin' powerful weapons.
But with influenza, it's more like spam. Not nearly as infectious, but there are lots of ways for influenza mutations to result in different-looking versions of still-effective influenza.
With influenza, changing its coat every season to avoid last year's antibodies is its well-evolved survival strategy.
With measles, having a super-effective precision infection skill is its well-evolved survival strategy, so it can't change its coat every season or it stops working.
So there are viruses that have a stable set of working copies, that we can easily vaccinate against, and there are viruses that have a potentially endless variety of working copies, that we cannot easily vaccinate against. Influenza and most of the common cold viruses -- some of which are coronaviruses, distant relatives of COVID -- have a potentially endless variety of working copies. COVID may end up being like influenza and most common cold viruses, with potentially endless varieties that can evade last season's antibodies.
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So what about HIV, why don't we have a vaccine for HIV, I asked Public Health Friend.
HIV is a retrovirus, a completely different category of virus -- "retro" meaning backwards, retroviruses work backwards compared to normal viruses, making them difficult for your immune system to fight. And HIV also specifically targets the immune system's cells, so when your T cells come sniffing around for HIV, the HIV infects them before the T cells can do anything about them, and blows them up. It's like HIV always wins the initiative roll against T cells and strikes first with a critical hit.
An RNA virus like COVID invades a cell and uses the cell's machinery to make new virus copies until the cell bursts from all these byproducts, releasing all the virus copies into the body. Retroviruses invade a cell and then copy themselves permanently into the DNA of the cell -- where they either lie dormant for a while, or they continually produce copies of themselves without destroying the host. Instead of bursting their host cells, new copies of HIV "bud" through the cell walls and then go looking for new hosts.
Your immune system cannot fix this embedded HIV DNA inside your cells. Your immune system is not designed to edit your own DNA. When your T cells look at an HIV-infected cell, it looks fine to them, there's no "virus" inside, only some updated DNA inside the cell nucleus. And your antibodies can chase after the new HIV viruses that are floating around in your blood, but they can't get to the embedded DNA inside your cells that keep producing new HIV. So antibodies for HIV cannot get rid of the source of the HIV infection. So a vaccine that produces HIV antibodies doesn't help much. HIV antibodies cannot cure you of, or even protect you from, an HIV infection, so producing HIV antibodies via an HIV vaccine is pointless.
HIV is also a slow burn infection. It can take years to ramp up inside your body. You can have this equilibrium where your HIV antibodies are cleaning up nearly all the HIV viruses that your HIV-infected cells are making, but over time a few of these new HIV viruses slip through the antibody net and infect new cells. Until finally, after years of this game, so many of your cells are making HIV that they overwhelm your antibodies and then wipe out your T cells, leaving you defenseless against secondary infections -- the stage of HIV infection known as Acquired Immune Deficiency Syndrome (AIDS).
Scientists found other ways to stop HIV, via antiviral drugs. They can block HIV from entering new cells, they can block HIV from creating new slices of HIV DNA, they can block HIV from updating your cell's DNA with slices of HIV DNA, and they can block new HIV copies from budding out of infected cells. They can do everything to stop HIV from infecting and replicating except -- to cure your already-infected cells. There's no drug that can edit the HIV DNA out from the inside of your cells.
BTW, this is how Prep works --> by blocking HIV from entering new cells, and if that fails, blocking HIV from creating new slices of HIV DNA to insert in your cells, and if that fails, blocking HIV from updating your cell's DNA with slices of HIV DNA. But Prep doesn't kill HIV, it just blocks it from working until it dies a natural death. Viruses usually don't live for long inside the human body if they can't infect a cell.
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It is possible to design antiviral drugs that block other kinds of viruses. We already have antivirals that block influenza, and plenty of scientists are working on new antivirals that would block COVID. But there's always the danger that viruses will mutate around specific antiviral drugs, that's why for HIV infection you have to take a triple-drug cocktail for the rest of your life, to block HIV from having any chance of replicating inside your body, so that it cannot even mutate.
Fun stuff!
But it is way more complicated than my description. This is the 5-minute version. Go study immunology for 10 years if you want to know how it all really works.
Yes!
Here was my question: Why do we need a flu vaccine every year, but we only need the measles vaccine once as kids? Doesn't the measles virus mutate as often as the influenza virus?
It took awhile for Public Health Friend to get to my point. Yes, the measles virus mutates as often as any other RNA virus. But he wanted to explain the different survival strategies and host populations of the two viruses. He felt I was using his field's terminology too loosely.
But I'll get to my point. Both measles and influenza are RNA viruses and they both mutate a lot, on average once per new virus particle. But measles is built like a precision missile -- it is super infectious against human cells -- and so each copy of the measles virus either works the same or it doesn't. There's not really any room for mutations to make measles even better, or to change how it looks. It's too precisely-well designed for infecting human cells. Most measles copies don't work, because of mutations, but the minority of true copies are fuckin' powerful weapons.
But with influenza, it's more like spam. Not nearly as infectious, but there are lots of ways for influenza mutations to result in different-looking versions of still-effective influenza.
With influenza, changing its coat every season to avoid last year's antibodies is its well-evolved survival strategy.
With measles, having a super-effective precision infection skill is its well-evolved survival strategy, so it can't change its coat every season or it stops working.
So there are viruses that have a stable set of working copies, that we can easily vaccinate against, and there are viruses that have a potentially endless variety of working copies, that we cannot easily vaccinate against. Influenza and most of the common cold viruses -- some of which are coronaviruses, distant relatives of COVID -- have a potentially endless variety of working copies. COVID may end up being like influenza and most common cold viruses, with potentially endless varieties that can evade last season's antibodies.
-----
So what about HIV, why don't we have a vaccine for HIV, I asked Public Health Friend.
HIV is a retrovirus, a completely different category of virus -- "retro" meaning backwards, retroviruses work backwards compared to normal viruses, making them difficult for your immune system to fight. And HIV also specifically targets the immune system's cells, so when your T cells come sniffing around for HIV, the HIV infects them before the T cells can do anything about them, and blows them up. It's like HIV always wins the initiative roll against T cells and strikes first with a critical hit.
An RNA virus like COVID invades a cell and uses the cell's machinery to make new virus copies until the cell bursts from all these byproducts, releasing all the virus copies into the body. Retroviruses invade a cell and then copy themselves permanently into the DNA of the cell -- where they either lie dormant for a while, or they continually produce copies of themselves without destroying the host. Instead of bursting their host cells, new copies of HIV "bud" through the cell walls and then go looking for new hosts.
Your immune system cannot fix this embedded HIV DNA inside your cells. Your immune system is not designed to edit your own DNA. When your T cells look at an HIV-infected cell, it looks fine to them, there's no "virus" inside, only some updated DNA inside the cell nucleus. And your antibodies can chase after the new HIV viruses that are floating around in your blood, but they can't get to the embedded DNA inside your cells that keep producing new HIV. So antibodies for HIV cannot get rid of the source of the HIV infection. So a vaccine that produces HIV antibodies doesn't help much. HIV antibodies cannot cure you of, or even protect you from, an HIV infection, so producing HIV antibodies via an HIV vaccine is pointless.
HIV is also a slow burn infection. It can take years to ramp up inside your body. You can have this equilibrium where your HIV antibodies are cleaning up nearly all the HIV viruses that your HIV-infected cells are making, but over time a few of these new HIV viruses slip through the antibody net and infect new cells. Until finally, after years of this game, so many of your cells are making HIV that they overwhelm your antibodies and then wipe out your T cells, leaving you defenseless against secondary infections -- the stage of HIV infection known as Acquired Immune Deficiency Syndrome (AIDS).
Scientists found other ways to stop HIV, via antiviral drugs. They can block HIV from entering new cells, they can block HIV from creating new slices of HIV DNA, they can block HIV from updating your cell's DNA with slices of HIV DNA, and they can block new HIV copies from budding out of infected cells. They can do everything to stop HIV from infecting and replicating except -- to cure your already-infected cells. There's no drug that can edit the HIV DNA out from the inside of your cells.
BTW, this is how Prep works --> by blocking HIV from entering new cells, and if that fails, blocking HIV from creating new slices of HIV DNA to insert in your cells, and if that fails, blocking HIV from updating your cell's DNA with slices of HIV DNA. But Prep doesn't kill HIV, it just blocks it from working until it dies a natural death. Viruses usually don't live for long inside the human body if they can't infect a cell.
-----
It is possible to design antiviral drugs that block other kinds of viruses. We already have antivirals that block influenza, and plenty of scientists are working on new antivirals that would block COVID. But there's always the danger that viruses will mutate around specific antiviral drugs, that's why for HIV infection you have to take a triple-drug cocktail for the rest of your life, to block HIV from having any chance of replicating inside your body, so that it cannot even mutate.
Fun stuff!
But it is way more complicated than my description. This is the 5-minute version. Go study immunology for 10 years if you want to know how it all really works.