delta 32

March 8, 2005 9:36 AM

If your European ancestors survived the Bubonic Plague 700 years ago, they very likely may have also passed on to you a mutation of the CCR5 gene -- called delta 32. This may not sound exciting, but delta 32 is a powerful mistake. HIV, the virus that causes AIDS, attacks the human immune system, infecting the white blood cells sent to destroy it. The delta 32 mutation, however, effectively blocks the crucial gateway into human cells the virus needs. In fact, possessing delta 32 could save your life, and the lives of your children.
posted by lola (47 comments total)

In fact, possessing delta 32 could save your life, and the lives of your children.

The last I read, there are certain behaviors, if one does not participate in those, which can keep you from HIV infection. That said, a very interesting post!
posted by Danf at 9:42 AM on March 8, 2005

The last I read, there are certain behaviors, if one does not participate in those, which can keep you from HIV infection. That said, a very interesting post!

Yes, for example: don't get raped, or get a life-saving transfusion with HIV-infected blood. Also, steer clear of Hemophilia, especially in the '80s.
posted by mullingitover at 9:48 AM on March 8, 2005

Some people have CD4 cells (cells that are part of the immune system machinery) that have mutated gp120 receptors that HIV can't bind to. A small segment (1%) of the population is partially immune to HIV for this reason.

These people have genetic mutations that change the shape of certain specific molecules on the surface of CD4 cells. Different strains of HIV can't bind to these differently shaped molecules the way they normally do. This imparts partial resistance. Other strains make their way in through other "doors".
posted by AlexReynolds at 9:50 AM on March 8, 2005

The last I read, there are certain behaviors, if one does not participate in those, which can keep you from HIV infection.

Don't know where you do your reading, but all "not participating" can do is lower your chances of infection in normal circumstances. There's always a chance - and in the event that the epidemic goes critical that chance will increase almost independant of your behavior.

Sure you didn't mean it this way, but the "Well I don't do those Bad Things so HIV can't effect me" thing really bothers me.
posted by freebird at 9:50 AM on March 8, 2005

"affect"
posted by freebird at 10:01 AM on March 8, 2005

There's always a chance - and in the event that the epidemic goes critical that chance will increase almost independent of your behavior.
Um, how so? Are you implying that I'm somehow going to become infected via blood contact with HIV+ people easily or the virus itself is going to change to cause the epidemic?
I think Danf meant "an easy way to avoid contraction of HIV is to have sex." Makes sense to me and I don't see the inflammatory responses being warranted for that.
posted by jmd82 at 10:05 AM on March 8, 2005

in the event that the epidemic goes critical that chance will increase almost independent of your behavior.

Simple logic. Even avoiding sex entirely, your chances of contraction, however minor, will still increase. Mingled blood via injury, blood transfusions, rape... all will be more likely to infect you with HIV if more of the general population already has it.

If you are having sex, but safely, the possibility of contraceptive failure is yet another extraneous variable. There is always a chance. And that chance looms larger, as more people contract HIV.
posted by mek at 10:19 AM on March 8, 2005

I think Danf meant "an easy way to avoid contraction of HIV is to have sex." Makes sense to me and I don't see the inflammatory responses being warranted for that.

Well, some of us have to deal with the reality of needle sticks and blood-borne pathogen exposure. But don't let that complicate your morality-based view of disease.

Also, as mullingitover mentioned, don't get raped. And make damn sure that your mother doesn't have AIDS; while mother-to-child transmission is declining, it still happens. You're also going to make sure that you're entirely celibate. None of this monogamous-relationship crap. You can't ever be entirely sure of your partner's fidelity and clean history.

While I'm at it, jmd82, yes, there is a possibility that the high rate of mutation that characterises HIV will allow the virus to become even more communicable. But that won't cause the epidemic -- the epidemic is already here.

Danf was clearly trolling. This post is about a gene that has a protective effect against HIV. The I'm-a-good-boy-so-this-isn't-relevant-to-me attitude is a stupid and dangerous way to look at this.
posted by LittleMissCranky at 10:21 AM on March 8, 2005

jmd83: Yes, you can avoid HIV by avoiding *all* sex and shared needles, however unless you can be absolutely certain your partner isn't sleeping around it's still possible to get it through "monogamous" (on your part) sex. It's also possible to get it by accidental coming across someone's blood, like in a car accident.

A teacher of mine was once riding a bus in africa which got into an accident, which shattered the non-saftey glass, causing his seatmate's blood to get all over him (in a country with a 25% HIV infection rate). Thankfully for him he didn't catch anything.

But I suppose you could add "Don't ride a bus in africa" to your list of things not to do.
posted by delmoi at 10:23 AM on March 8, 2005

Also, in the in the spirit of non-derailment let's try to get the discussion back on track by talking about genetics!

DNA is neat.

Thank you.
posted by delmoi at 10:25 AM on March 8, 2005

I'm with freebird, maybe it was just stated in a coldly analytical fashion, but I can't help but see the responses here reading a subtext "I'm not a heroin user afflicted with a case of teh gay so no worries, mate" Maybe us lefties just think too much into, you know, being considerate of others and all, just.. meh.

on preview: Yes yes! Let's get back to this! I love mutation! And evolution! And sequencing! This is wacky stuff.
posted by cavalier at 10:27 AM on March 8, 2005

Mullingitover, don't forget to be certain that your spouse does not participate in those behaviors. That helps a lot.

This is really interesting news. Good post.
posted by theora55 at 10:28 AM on March 8, 2005

If my European ancestors did not survive the Bubonic Plague 700 years ago, then I guess I don't exis *vanishes from existence*
posted by serafinapekkala at 10:28 AM on March 8, 2005

Sera: Unless, of course, they happened have gotten the plague after they had kids.
posted by Mercaptan at 10:33 AM on March 8, 2005

Reminds me of how sickle-cell anaemia provides some immunity to malaria. Interesting how some things work out.
posted by randomstriker at 10:38 AM on March 8, 2005

serafinapekkala has the Best Name and gets today's Weak Anthropic Principle joke award! My Hero!

just to be clear, the "weak" refers to the version of the Principle, not the joke. Though as Mercaptan points out, it's not quite accurate in biological terms :)

Agreed about getting back to genetics, but I must point out that arguing about the mechanism of a selection pressure isn't entirely a derail - and the idea that "good behavior" guarantees HIV avoidance is in effect a misunderstanding of such.

randomstriker - was thinking the same thing, but isn't this a little different: is there a negative aspect to possessing delta 32? That general principle, though, is the best argument against eugenics in all its forms.
posted by freebird at 10:41 AM on March 8, 2005

Fascinating post, lola, thanks!
posted by knave at 10:46 AM on March 8, 2005

The Bubonic Plague struck Europe in 1348 for the first time since the 6th century. It was later called "The Black Death" because one of the symptoms is black skin caused by blood rising to the surface. Contrary to popular perception the Black Death was not a single event but returned every generation until the 17th century, although the initial 1348 event was by far the most lethal. It was a fact of life for 100s of years. No one knows exactly why the Bubonic Plague disappeared between the 6th and 14th century as it was not uncommon in the ancient world.
posted by stbalbach at 11:14 AM on March 8, 2005

So now they can figure out how to do the gene therapy to insert that delta 32.
posted by edmo at 11:24 AM on March 8, 2005

This sounds similar to the sickle cell anemia mutation that some african americans have. (on preview what randomsticker said)

I've just finished reading Matt Ridley's Genome and have so many fun facts about genetics running through my head these days. On one level, I'd like to have some genetic testing done. But that can be a misguided effort too. Some cases of a disease can have a genetic cause, but that doesn't mean that all cases of that disease will be genetically caused. So I might be tested and think I'm safe but really I'm only safe from that cause. I could get it another way. I'm thinking of breast cancer as a easy example of this.
posted by Red58 at 11:31 AM on March 8, 2005

Taking part in certain acts increases your chances of attaining the HIV virus. We can argue all day about whether or not these behaviors (drug use, promiscuity, homosexuality) are immoral - and I'm not saying they are - but ignore the fact that these acts often lead to this virus is retarded.

Yes, for example: don't get raped, or get a life-saving transfusion with HIV-infected blood. Also, steer clear of Hemophilia, especially in the '80s.

So if I told you I was scared of dying in a plane crash and therefore don't fly, would you tell me to avoid living or travelling in existing flight paths because, you never know, a plane could just crash on top of my head? Because that's basically the argument you made right there.
posted by b_thinky at 11:32 AM on March 8, 2005

Unless, of course, they happened have gotten the plague after they had kids.

But those kids are still Sera's ancestors, and they survived. I suppose everybody with European ancestry had a forebear who died of plague, but I like Sera's point that somebody important survived for each one of us.
posted by PhatLobley at 11:33 AM on March 8, 2005

I recently attended a seminar about this. Turns out, smallpox [pdf] may be a better candidate for explaining the mutation. Either way, nifty stuff.

And freebird, as far as I know (read here, as far as the person giving the seminar knew), there are no known deleterious effects to the CCR5 mutation.
posted by solotoro at 11:33 AM on March 8, 2005

>Yes, for example: don't get raped, or get a life-saving transfusion with HIV-infected blood. Also, steer clear of Hemophilia, especially in the '80s.

So if I told you I was scared of dying in a plane crash and therefore don't fly, would you tell me to avoid living or travelling in existing flight paths because, you never know, a plane could just crash on top of my head? Because that's basically the argument you made right there.

Er, actually, I think they were pointing out the foolishness of the "HIV can be avoided completely through behavior modification" argument by listing HIV infection vectors that could not be predicted or consciously avoided as if they could be. You know, to highlight how absurd that other person's argument was.
posted by davejay at 12:16 PM on March 8, 2005

Way to ruin a thread guys..
posted by eas98 at 12:23 PM on March 8, 2005

I'm probably just out of the loop, but it seems strange that to me that the knowledge that this mutation inhibits HIV infection has been around for almost a decade, and was not huge news. Maybe because attempts to apply it to a cure/treatment havent been that sucessful yet. My immediate thought on reading the article was - is it possible to bring the advantages of this mutation to other people? Is it possible to change someone's genes?

But my heart falls to hear that this mutation does not occur in African populations, where AIDs is so ravaging people of all ages, sex and sexual orientation.
posted by jb at 12:33 PM on March 8, 2005

b_thinky writes:Taking part in certain acts increases your chances of attaining the HIV virus. We can argue all day about whether or not these behaviors (drug use, promiscuity, homosexuality) are immoral - and I'm not saying they are - but ignore the fact that these acts often lead to this virus is retarded.

Drug use and homosexuality are not vectors for HIV transmission, and anyone who says so is retarded. IV drug use and unprotected sex acts are both vectors for the spread of HIV. The last time I checked HIV didn't know the difference between hetero- and homo-sex, and it can't be spread by, for instance, pipe smoking.
posted by OmieWise at 12:39 PM on March 8, 2005

Hey, everyone who people in general would be better off NOT DYING OF A DISEASE THAT LEAVES YOU WEAK AND POWERLESS, raise your hand!

All right, good. So. Irony of disease, that's cool. What are the implications for future research? What parallels can we draw? The malaria thing's cool, if even more bittersweet.
posted by NickDouglas at 12:55 PM on March 8, 2005

I read an article about feline immuno virus (FIV) that said the virus is highly prevalent, though harmless, in big cat populations. It's likely that at some point in the distant past it decimated their numbers, but the survivors passed on their immunity so that today FIV has no negative impact. Perhaps after several generations HIV will go the way of FIV... though I suspect the world-wide infection rate would have to be much higher than it currently is in order for a similar natural selection to take place...

On the other hand FIV is still deadly in domestic cat populations, dunno why ....
posted by crank at 1:13 PM on March 8, 2005

So now they can figure out how to do the gene therapy to insert that delta 32.

Awesome and ironic: what's one of best ways to apply gene therapies to living organisms? Modified versions of HIV...

Way to ruin a thread guys..

Oh shush.
posted by freebird at 1:47 PM on March 8, 2005

Okay, back on task. . .

As mentioned, the mutation in the CCR5 gene is a little different from the HBB mutation that causes sickle cell. The sickle cell gene was positively selected for because a single copy of the gene provides malaria protection without actually giving you sickle cell. It's when you get two copies that you have the disease. That's also why sickle cell has a much higher incidence among people of african, mediterranean, indian, and middle eastern descent -- i.e., people whose ancestors were most likely to have been exposed to malaria.

CCR5 seems to be an entirely beneficial mutation, although there is some suspicion that it may increase susceptibility to Hepatitis C. Unlike the HBB mutation, a single copy of CCR5 provides some protection, but two copies provides a whole lot more. The hypothesis that it also provided plague immunity seems to be erroneous, so now they're checking out smallpox.

AlexReynolds, I'm not sure if you're aware of this or not, but the gp120 receptor is not what's affected by the CCR5 mutation. The gp120 receptor is the receptor that HIV binds to on the CD4 T cell. CCR5 encodes a cytokine receptor. A mutation in either one seems to provide some resistance to HIV, but the cytokine receptor seems to be the more crucial piece.
posted by LittleMissCranky at 2:02 PM on March 8, 2005

So if it's not interfering with the protein binding to T cells, how does the mutation interfere with the viral life cycle? The article was a bit short on details. I know HIV does a lot of really tricky "signalling" to itself and variant splicing as part of its life cycle, is that what gets interfered with?
posted by freebird at 2:15 PM on March 8, 2005

It is disputed whether the Black Death was, in fact, Bubonic Plague. It has long been considered the case as a matter of course, but recently scientists have cast doubt on this. The symptoms and incubation period of the two diseases, for instance, doesn't match.
posted by cx at 2:30 PM on March 8, 2005

freebird, I believe it DOES interfere with the binding to the T-cell. CCR5 is a coreceptor for HIV1.
posted by solotoro at 2:39 PM on March 8, 2005

(I'm probably using the wrong terminology; I'm no biochemist.)
posted by solotoro at 2:45 PM on March 8, 2005

Bug up the caucasian massive! Not only do we have a higher probability of some HIV resistance, but we also have a higher probability of being able to digest milk sugars while adults, and also metabolise alcohol faster.
posted by meehawl at 3:06 PM on March 8, 2005

Modified versions of HIV...

In William Gibson's novel Virtual Light, there's a significant subplot involving a character, JD Shapely, who winds up being sort of a modern genetic messiah figure. He apparently posesses a chance genetic mutation that makes him immune to HIV, and his "gift" is reverse-engineered and administered to people via genetic therapy to share the immunity.
posted by alumshubby at 3:19 PM on March 8, 2005

Hooray for white people!

alumshubby: I thought in Virtual Light, the guy has a form of "anti-HIV" which he spread by having sex with lots and lots of people.

Maybe I'm thinking of a different sf novel.
posted by neckro23 at 3:42 PM on March 8, 2005

freebird, I believe it DOES interfere with the binding to the T-cell. CCR5 is a coreceptor for HIV1.

Yep, that's right. For HIV to be taken up into T cells, two things need to happen: (1) HIV has to bind to the cell, and (2) the cell has to receive a second signal, which can be provided by the HIV itself. Interfering with either of these steps gives resistance to the virus. Sorry, freebird -- I was a little confusing.
posted by LittleMissCranky at 6:13 PM on March 8, 2005

Ah, OK, that fits better with the little I know about the lifecycle.
Thanks!

So, presumably human processes have another way to get the signal through. Wouldn't HIV just rapidly come up with one itself? The last time I worked in biotech, HIV as a "metapopulation" was all the buzz, and the associated ability to adapt and mutate astoundingly quickly and well...
posted by freebird at 6:54 PM on March 8, 2005

I am currently working on CCR5 myself, and our research group have found that the d32 mutation is protective against the autoimmune disease rheumatoid arthritis, and may also protect carriers against other autoimmune disorders, too. Thus persistance in the popuation may also be influenced by other factors than viral infection. We are looking now at a number of other immune-cell related genes which have been identified in altering susceptibility to HIV for relationships with autoimmunity, as well.
What I find most interesting about this work is the balance between genetic pressures which have favoured a robust immune response in environments where we faced continual exposure to pathogens, and our sterilised Western cultures where the absence of external challenges to our immune system render this responsiveness a liability (characterised by increasing incidence of allergies, asthma, type 1 diabetes ant other autoimmune disorders-the so called germ-free theory of autoimmunity)
posted by MadOwl at 3:29 AM on March 9, 2005

neckro123, probably I'm misremembering the novel. That explains the quasi-messiah slant better. Been a few years since I read it.
posted by alumshubby at 4:20 AM on March 9, 2005

wouldn't the ancestor have needed to get the plague and then survive for his genes to have been affected? Did people get it and live, or was it only those people who didn't get it that lived to become our ancestors? (oh, and Kim Robinson's Years of Rice and Salt also uses the plague)

and someone explain how bacteria affects our genes anyway, please--we're surrounded by it and full of it all the time anyway, no?

and with all the mutations (some caused by the drugs themselves), can this help find a cure? vaccine? something?
posted by amberglow at 9:24 AM on March 9, 2005

oh, also, semi-related: i'm thinking the mutations will eventually result in an HIV that doesn't kill its hosts, since that doesn't make sense if survival is really the principal law of life. it's always bothered me about that.
posted by amberglow at 9:29 AM on March 9, 2005

Is it possible to change someone's genes?
Aye, it is. Gene therapy where genes within people are altered is currently a hot topic for research. The problem with implementing new genetic material information such as mutations in this case is we don't know the long or short-term side effects. People have this mutation from birth- the consequences of introducing mutations at a random time could be drastic.

oh, also, semi-related: i'm thinking the mutations will eventually result in an HIV that doesn't kill its hosts, since that doesn't make sense if survival is really the principal law of life. it's always bothered me about that.
But think about it: AIDS is living on for a very very long time in organisms as compared to most viruses. With sufficient drugs, you could hypothetically live the rest of your life with AIDS. Even without drugs, you can live for a few years with AIDS. Because of the drugs allowing someone to live so much longer with AIDS, the likelihood of a mutation to extend the host's life being selected for is that much more reduced (and keep in mind the likelihood of such a significant mutation being selected for even in favorable conditions is very low).

The last time I checked HIV didn't know the difference between hetero- and homo-sex, and it can't be spread by, for instance, pipe smoking.
You're right. However, the difference is certain lifestyles give a higher propensity towards contraction of AIDS. My not having sex (hetero of homo) gives me less a chance of contracting AIDS then someone who sleeps around. I never claimed a moral judgement about certain lifestyles- you all jumped to conclusions.
posted by jmd82 at 9:40 AM on March 9, 2005

and with all the mutations (some caused by the drugs themselves), can this help find a cure? vaccine? something?
Eh, that's one of the main problem with AIDS: the genetic material copying machinery is highly inaccurate which cause a mutation allowing that cell to escape death (as in a mutation renders a drug useless). In contrast to my last post about the low likelihood of a mutation being selected for, the chances here of the mutation being selected for is very high because the conditions for that mutated cell to propagate is very high.
posted by jmd82 at 9:45 AM on March 9, 2005

oh...thanks. : <
posted by amberglow at 9:47 AM on March 9, 2005