Good
news for lactose TOLERANT Scandanavians!
During our
AIDS lecture, we learned that there is a population of people who are
relatively resistant to HIV infection. These people are either heterozygous or
homozygous for a mutant CCR5 allele (called Delta32). Remember: CCR5 is a
chemokine receptor that serves as a co-receptor in the process by which T cells
are infected with HIV particles. Without this receptor, T cell infection is
greatly inhibited, and these people will have virus within their bodies but may
remain “healthy” for a long period of time before they do eventually progress
to AIDS (I assume that T cells are eventually infected through some other
manner?). Anyway, I began to wonder who
are these lucky people with this mutant allele, and HOW did this allele evolve?
These people are Caucasians, and mostly Scandanavian (Norway, Finland, Sweden, see top picture below). It had been proposed, and is still the dominant theory out there, that this allele evolved from selective pressure from the Bubonic plague. However, a new(ish) article published in the Oxford Journal of Medicine (1) performed an extensive analysis of this hypothesis. It turns out that the places hit the hardest by the Bubonic plague were northern Africa, Asia, the Middle east, ETC. but NOT northern Europe (see bottom picture below). Plague did reach Norway and Sweden and eventually Finland, although it returned there only a few times compared with dozens of times to the hardest hit areas. So, could the bubonic plague have realistically been the evolutionary pressure by which the CCR5 mutant allele expanded? According to this article, this is highly unlikely. SO then, what WAS the evolutionary pressure?
Figure 1: Population frequencies of the CCR5-Δ32 allele (upper section: black >10%, dark grey 6–10%, pale grey <6%) and Black Death mortalities 1346–53 (lower section: black >50%, dark grey 25–50%, pale grey <25%) in Europe. Based on data from Stephens et al.1 For computer-simulated maps, see Novembre et al.2 (Taken from Cohen and Weaver, 2006)
This may seem
out there, crazy, etc. (especially because it remains untested) but I think it
is very interesting. Upon trying to
understand what could be different between these populations (people with the
mutant allele versus without) they stumbled upon the fact that most
scandanavians are lactose TOLERANT. Whereas, many of the other countries listed
above (Africa, Asia, Middle East) have higher incidences of lactose
INTOLERANCE (1). Could the ingestion of dairy placed positive evolutionary pressure upon
the mutant CCR5 allele? What do you think??
How would you test this hypothesis?? (I am asking because I have no idea).
(1) S.K. Cohn Jr andL.T. Weaver. The Black Death and Aids: CCR5-Δ32 in genetics and history.QJM: An International Journal of Medicine Volume 99, Issue 8, p. 497-503.
I think T-cells can be infected through CXCR4 in addiction to CD4 so maybe this is how T-cells are still depleted in CCR5 deficient humans. HIV could probably still infect macrophages in these people too even though CCR5 is gone so it is interesting how in bone marrow transplants with CCR5 deficient they claim HIV cured. I wonder if it is really cured or just hiding out in macrophages somewhere. Did the plague also use CCR5 to infect?
ReplyDeleteI was wondering the same thing. Although, CCR5 is also expressed on macrophages, they won't be infected. Same for microglia. They all are CD4+ cells expressing CCR5. Is that right? Dendritic cells express CCR5 but there an alternative root for HIV to enter DC: lectic called CD-SIGN. I think the virus will always be in the system but it won't cause any symptoms nor it will progress to AIDS. Please correct me if I am wrong!
ReplyDeleteMy personal view is that the Black Death wasn't plague (wrong epidemiology), but that's another story. The delta32 mutation seems to have been selected before the 14th century when the Black Death raged. The best guess is that delta32 conferred relative resistance to smallpox, which has been around forever; and poxviruses commonly use chemokine receptors as attachment sites. Take a look at:
ReplyDeletehttp://www.pnas.org/content/100/25/15276.long
I wish I had found this article sooner! Sure seems like a more likely hypothesis than lactose tolerance.
Delete@RossO- apparently the bacterial pathogen of the bubonic plague, Yersinia pestis, does not utilize CCR5 for cellular entry therefore a defiency in CCR5 is unlikely to provide resistance to the plague (Metzger).
ReplyDeleteI think the correlation between the increased frequency of the CCR5-delta32 allele alongside the increased frequency of lactose tolerance is definitely an interesting and logical theory. I tried to find more information on the subject, such as what sort of positive pressures regarding lactose tolerance would select for CCR5-delta32 allele, but I could not find anything substantial.
Very interesting, though!
http://books.google.com/books?id=Qm4iSx2HsqUC&lpg=PA12&ots=6LCTzWan8P&dq=lactose%20tolerance%20ccr5&pg=PA13#v=onepage&q=lactose%20tolerance%20ccr5&f=false
It's interesting that this was posted here on our blog site, when we just learned about this in microbiology. We learned about the Palgue theory but not the lactose tolerance versus intolerance. I think something simple like lactose tolerance and intolerance cannot really affect a complex disease like HIV, and if it did, I would have expected researchers to have discovered that already. That's just my theory on the it all.
ReplyDeleteOne more thing we did talk about in my microbio class was a presentation of a man, from I think it was Norway, who held a TED talk about HIV, its rate of transmission and different habits in different parts of the world. He really stressed the misconcieved 'facts' people have about Africa and their AIDS epidemic. Something else that was brought up there was about sexual habits that affects the rate of transmission in Africa and then in northern Europe. It was sait that in terms of sexual partners, in northern Europe the average monogamous relationship lasts about 6 months. HIV's spread is best the first 2-8 weeks. But in Africa having multiple partners is not uncommon, so the disease is spread a lot faster, more efficiently (from the view of the virus) and differently than it would spread in Europe. I just thought that was interesting... the talk was short and actually really interesting. Here is the link for anyone interested:
http://www.ted.com/talks/hans_rosling_the_truth_about_hiv.html
I am a lactose tolerant Scandinavian from the Mid-west. And as the holidays approach and the influx of other lactose tolerant Scandinavians come to visit loaded with ice boxes of cheese and butter your title really drew me in! I cannot wait to toss the hypothesis around to them which I am sure they will drink whole milk merrily to and douse their leftover ham sandwiches with butter, cheese, and booze.
ReplyDeleteIn my attempts to come up with a novel experiment to test this hypothesis I have scoured the internet for inspirations but could not find one. Even though this blog will be ending grading wise, I plan on taking this back to my fellow Swedish Wisconsinites for ideas and will get back to you after the holiday!
Good post CB!I am Nigerian and lactose intolerant and part of the reason many people in Africa are lactose intolerant is because for a long time, there was no way to store dairy and the warm African climate made dairy too easy to spoil. So I wonder if there had been more lactose tolerant Africans, how that would affect the HIV/AIDS rate.
ReplyDelete